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Erratum Erratum to (Impact of Yoga and Meditation on Cellular Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study) Madhuri Tolahunase, 1 Rajesh Sagar, 2 and Rima Dada 1 1 Lab for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences (AIIMS), New Delhi, India 2 Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi, India Correspondence should be addressed to Rima Dada; rima dada@rediffmail.com Received 9 August 2017; Accepted 28 August 2017; Published 24 September 2017 Copyright © 2017 Madhuri Tolahunase et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In the article titled “Impact of Yoga and Meditation on Cellu- lar Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study” [1], there were a number of language errors, due to publisher error. e corrected version of the article is shown below: Abstract is study was designed to explore the impact of a yoga- and meditation-based lifestyle intervention (YMLI) on cellular aging in apparently healthy individuals. During this 12-week prospective, open-label, single-arm exploratory study, 96 apparently healthy individuals were enrolled to receive YMLI. e primary endpoints were assessment of the change in levels of cardinal biomarkers of cellular aging in blood from baseline to week 12, which included DNA damage marker 8-hydroxy-2 -deoxyguanosine (8-OH2dG), oxidative stress markers reactive oxygen species (ROS), and total antioxidant capacity (TAC), and telomere attrition markers telomere length and telomerase activity. e secondary endpoints were assessment of metabotrophic blood biomarkers associated with cellular aging, which included cortisol, -endorphin, IL- 6, BDNF, and sirtuin-1. Aſter 12 weeks of YMLI, there were significant improvements in both the cardinal biomarkers of cellular aging and the metabotrophic biomarkers influencing cellular aging, compared to baseline values. e mean levels of 8-OH2dG, ROS, cortisol, and IL-6 were significantly lower and mean levels of TAC, telomerase activity, -endorphin, BDNF, and sirtuin-1 were significantly increased (all values < 0.05) post-YMLI. e mean level of telomere length was increased but the finding was not significant ( = 0.069). YMLI significantly reduced the rate of cellular aging in an apparently healthy population. 1. Introduction In the last decade there has been a significant increase in complex lifestyle diseases like depression, diabetes mellitus (DM), cardiovascular diseases (CVD), cancer, and infertil- ity. ese diseases are strongly associated with accelerated cellular aging [1, 2] and have become the bane of modern society [3–5]. Within a homogeneous sample of an apparently healthy adult population, biomarkers have been defined recently [6] to characterize the complex processes of an accelerated aging phenomenon. Although we do not have any gold standard biomarker to monitor healthy aging, based on the current knowledge of putative biomarkers, the cardinal biomarkers of cellular aging and metabotophic biomarkers that can influence them have become the focus of the latest translational research to develop interventions to prevent chronic lifestyle diseases. e cardinal biomarkers of cellular aging include DNA damage, telomere length attrition, and oxidative stress (OS) [7]. DNA damage causes genomic instability, which is Hindawi Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 2784153, 7 pages https://doi.org/10.1155/2017/2784153

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Page 1: Erratum - Hindawi

ErratumErratum to (Impact of Yoga and Meditation on CellularAging in Apparently Healthy Individuals A ProspectiveOpen-Label Single-Arm Exploratory Study)

Madhuri Tolahunase1 Rajesh Sagar2 and Rima Dada1

1Lab for Molecular Reproduction and Genetics Department of Anatomy All India Institute of Medical Sciences (AIIMS)New Delhi India2Department of Psychiatry All India Institute of Medical Sciences (AIIMS) New Delhi India

Correspondence should be addressed to Rima Dada rima dadarediffmailcom

Received 9 August 2017 Accepted 28 August 2017 Published 24 September 2017

Copyright copy 2017 Madhuri Tolahunase et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

In the article titled ldquoImpact of Yoga andMeditation on Cellu-lar Aging in Apparently Healthy Individuals A ProspectiveOpen-Label Single-Arm Exploratory Studyrdquo [1] there werea number of language errors due to publisher error Thecorrected version of the article is shown below

Abstract

This study was designed to explore the impact of a yoga- andmeditation-based lifestyle intervention (YMLI) on cellularaging in apparently healthy individuals During this 12-weekprospective open-label single-arm exploratory study 96apparently healthy individuals were enrolled to receive YMLIThe primary endpoints were assessment of the change inlevels of cardinal biomarkers of cellular aging in blood frombaseline to week 12 which included DNA damage marker8-hydroxy-21015840-deoxyguanosine (8-OH2dG) oxidative stressmarkers reactive oxygen species (ROS) and total antioxidantcapacity (TAC) and telomere attrition markers telomerelength and telomerase activityThe secondary endpoints wereassessment of metabotrophic blood biomarkers associatedwith cellular aging which included cortisol120573-endorphin IL-6 BDNF and sirtuin-1 After 12 weeks of YMLI there weresignificant improvements in both the cardinal biomarkers ofcellular aging and the metabotrophic biomarkers influencingcellular aging compared to baseline values The mean levelsof 8-OH2dG ROS cortisol and IL-6 were significantly lower

and mean levels of TAC telomerase activity 120573-endorphinBDNF and sirtuin-1 were significantly increased (all values119901 lt 005) post-YMLI The mean level of telomere length wasincreased but the finding was not significant (119901 = 0069)YMLI significantly reduced the rate of cellular aging in anapparently healthy population

1 Introduction

In the last decade there has been a significant increase incomplex lifestyle diseases like depression diabetes mellitus(DM) cardiovascular diseases (CVD) cancer and infertil-ity These diseases are strongly associated with acceleratedcellular aging [1 2] and have become the bane of modernsociety [3ndash5]Within a homogeneous sample of an apparentlyhealthy adult population biomarkers have been definedrecently [6] to characterize the complex processes of anaccelerated aging phenomenon Althoughwe do not have anygold standard biomarker to monitor healthy aging based onthe current knowledge of putative biomarkers the cardinalbiomarkers of cellular aging and metabotophic biomarkersthat can influence them have become the focus of the latesttranslational research to develop interventions to preventchronic lifestyle diseases

The cardinal biomarkers of cellular aging include DNAdamage telomere length attrition and oxidative stress (OS)[7] DNA damage causes genomic instability which is

HindawiOxidative Medicine and Cellular LongevityVolume 2017 Article ID 2784153 7 pageshttpsdoiorg10115520172784153

2 Oxidative Medicine and Cellular Longevity

responsible for cellular dysfunction in the pathogenesis oflifestyle diseases [8ndash10] OS is the most important causeof DNA damage Although many different oxidative DNAdamage (ODD) products have been identified 8-OH2dG (8-hydroxy-21015840-deoxyguanosine) a highly mutagenic oxidativeDNA adduct has been the subject of intensive study and is adefinitive biomarker of DNA damage [11] Telomere attritionis due to altered telomere metabolism involving a decreasein telomerase enzyme activity and an increase in OS Itcontributes to genomic instability and is associatedwith agingand lifestyle diseases [12]

Oxidative stress an imbalance between prooxidants andantioxidant defense mechanisms becomes pathological atboth extremes of the physiological range needed for normalcellular functions It is involved in the pathogenesis of com-plex lifestyle and chronic diseases [13] including depression[14] obesity [15] and infertility [16 17] the leading publichealth problems

Several metabotrophic blood biomarkers influencing cel-lular aging include biomarkers of stress and inflamma-tory response neuroplasticity and longevity Sustained stressresponses due to chronic stress stimuli cause constantlyincreased cortisol levels [18] which lead to systemic tissueabnormalities like increased adiposity and neurodegener-ation The level of stress responsiveness (cortisol levels)can be a biomarker for predicting susceptibility to lifestylediseases [19] Accelerated aging is characterized by a chroniclow-grade inflammation (ldquoinflammagingrdquo) Inflammaging isa highly significant risk factor for most chronic lifestylediseases [20] and is a potential modifiable target [21] IL-6is the most prominent cytokine in inflammaging and is botha marker of inflammatory status and a hallmark of chronicmorbidity [22] Impaired neuroplasticity due to acceleratedaging can have negative influence across the entire lifespan[23] BDNF is amajor regulator of neuroplasticity [24] whichmay be increased in specific regions of the brain by variousinterventions [25] Health span and longevity are influencedby several factors Sirtuin-1 (SIRT1) a histone deacetylase(HDAC) is prominent among them and recently has becomea target for various interventions [26] It systemically influ-ences nutrition and energy metabolism and centrally has arole in circadian rhythm survival against stress [27] andneuronal plasticity [28]

A variety of interventions have been studied [29 30] todetermine their influence on preventing lifestyle diseases andpromoting health and longevityThey include treatments tar-geting specific hallmarks of aging namely physical exercise[31] nutrition caloric restriction [32] and antioxidants [33]However no single intervention is shown to be an effectivepreventive and therapeutic strategy for modern complexlifestyle diseases and to provide comprehensive benefits fordelaying or reversing accelerated aging Therefore furtherresearch is needed to find optimum interventions for pop-ulation at risk of lifestyle diseases Yoga is an emergingintegrative health discipline which can positively modulatemind and body [34] and has been shown to improve theclinical profile of patients with various pathologies [35]including depression obesity hypertension asthma type IIdiabetes and cancerHowever recent reviews on yoga suggest

that potential underlying mechanisms need to be furtherexplored [36] Studies on biomarkers of disease and health inyoga-based interventions are limited and they have only high-lighted diabetic and lipid profiles [37 38] stress and inflam-matory markers [39 40] and neuroimaging correlates [41]in populations with specific medical conditions Evidence islacking regarding the efficacy of yoga lasting a short durationof 3 to 12 weeks in improving the biomarkers of cellular agingin apparently healthy people Thus the present study wasdesigned to evaluate the impact of a yoga- and meditation-based lifestyle intervention (YMLI) on cellular aging andlongevity by analyzing cardinal and metabotrophic biomark-ers in the peripheral blood of apparently healthy subjects

2 Materials and Methods

21 Study Design and Participants Ninety-six apparentlyhealthy people were enrolled in this 12-week prospectiveopen-label single-arm exploratory study from August 2015to May 2016 designed to explore the impact of YMLI oncellular aging The key inclusion criteria were male or femaleaged 30ndash65 years and leading an unhealthy modern lifestyleThe key exclusion criteria were inability to perform the yogicexercises due to any physical challenges and those with recentchanges in lifestyle during the last 3 months The study wasinitiated after ethical clearance (ESCT-37022-07-2015) andthe registration of the trial with the Clinical Trial Registry ofIndia (CTRI REF201409007532)

22 Procedure

221 Yoga- and Meditation-Based Lifestyle Intervention(YMLI) Eligible subjects were enrolled in the study afterscreening and baseline characteristics were recorded Par-ticipants underwent a 12-week pretested YMLI programcomprising theory and practice sessions [42 43] YMLI isdesigned to be an integrative health strategy incorporatingthe classic components of yoga including asanas (physi-cal postures) pranayama (breathing exercises) and dhayna(meditation) which are derived fromamix ofHatha yoga andRaja yogaThe YMLI for the current study was suitably mod-ified for apparently healthy subjects YMLI program includedsessions five days per week for 12 weeks For the first twoweeks the sessions were held at the integrated health clinic(IHC) AIIMS New Delhi and taught by registered spe-cialized yoga instructors (educational qualifications includeBachelor ofNaturopathy andYoga Sciences and PGDiplomain YogaTherapy) The remaining 10 weeks were home basedMonitoring of compliance of the home-based YMLI wasthrough maintenance of a diary and telephonic contact Thedetails of the activities in a day during the YMLI programare given in Table 1 Each session in YMLI included a set ofasanas pranayama and dhayna for approximately 90 min-utes This was followed by an interactive lecture (only duringthe first two weeks of YMLI at IHC) on lifestyle lifestylediseases and importance of their prevention for 30 minutes

222 Laboratory Procedures During this 12-week study theparticipants were evaluated for various biomarkers on day

Oxidative Medicine and Cellular Longevity 3

Table 1 Details of activities in a day of Yoga- and Meditation-based Lifestyle Intervention (YMLI) program

S No Practice to be done Duration(1) Session preparation instructions 5min

(2) Prayer 3minLoosening practices (warm-up) 5min

(3) Asanas (Postures)

SupineShavasana 2min

Uttanpadasana 2minPawanmuktasana 2min

ProneMakarasana 2minBhujangasana 2minSalabhasana 2min

SittingVakrasana 2min

Ardha-Matsyendrasana 2minVajrasana 2min

StandingTadasana 2min

Vrikshasana 2minArdhachakrasana 2min

(4) Relaxation Shavasana 5min

(5) Pranayama (Breathing Exercises)

Nadishodhana

20minBhramriShitkariShitali

Brahmamudra(6) Aumkar recitation 3min(7) Dhyana (Meditation) 20min(8) Shanti mantra 5min

(9)Interactive session (first 2 weeks only atIntegrated Health Clinic AIIMS New

Delhi)30min

Total 120min

0 and week 12 Fasting venous blood samples (5mL) werecollected and divided into two parts One part was allowedto clot and the serum was separated within 30minutes andthe other part was transferred to heparinizedEDTA vialsand was centrifuged at 2000119892 for 15 minutes at 4∘C Bothserum and plasma were stored at minus80∘C until analyzed ROSdetection was done by chemiluminescence assay (Bertholddetection luminometer USA) Peripheral blood leukocytetelomere lengthwasmeasured by qPCR and telomerase activ-ity was determined by using a telomerase assay kit (RocheSwitzerland) as per the manufacturerrsquos protocol 8-OH2dGwas estimated in white blood cell DNA (Caymanrsquos EIA kit)ELISA kits were used for levels of TAC (Cayman ChemicalAnn Arbor USA) cortisol (DRG Diagnostic Germany)120573-endorphin (Phoenix Pharmaceuticals Inc) IL-6 (Gen-Probe Diaclone Diagnostic France) BDNF (RaybiotechInc) and sirtuin-1 (Quayee Bio-Technology) Quality controlassays for biomarkers and validation were performed

223 Endpoints The primary endpoint was to assess thechange in levels of cardinal biomarkers of cellular aging frombaseline to week 12 The biomarkers included the following

8-OH2dG ROS and TAC (markers of OS and ODD) aswell as telomere length and telomerase activity (telomereattritionmarkers)The secondary endpoints were assessmentof metabotrophic blood biomarkers associated with cellularaging which included cortisol 120573-endorphin IL-6 BDNFand sirtuin-1 from baseline to week 12

23 Statistical Analysis Data were analyzed using SPSS 20(IBM Corp Armonk NY) Descriptive statistics are reportedas means and standard deviations Changes in outcome vari-ables were analyzed using paired-samples t-tests Exploratoryanalysis included comparisons for within gender subgroupsusing paired-sample t-tests Significance was accepted at 119901 lt005

3 Results

Theflowdiagramof participant details is provided in Figure 1Of 96 subjects 94 subjects were assessed for impact analysisTwo subjects were excluded from the analysis due to poorcompliance to the program Baseline sociodemographic char-acteristics are shown in Table 2

4 Oxidative Medicine and Cellular Longevity

Assessed for eligibility (n = 120)

Excluded (n = 24)

Not meeting inclusion criteria (n = 15)

Declined to participate (n = 9)

Enrolled (n = 96) to receive YLMI for

12 weeks

Analyzed (n = 94)

Dropped out from YMLI (n = 2)

Figure 1 Flow diagram of study participation

Table 2 Sociodemographic characteristics of participants

Variable ValuesAge (years) 4026 (1013)Sex

Female 52 (5532)Male 42 (4468)

Socioeconomic statusKuppuswamy socioeconomic status scale

Education 482 (124)Occupation 526 (238)Income 860 (274)Total 1868 (734)

BMI (kgm2) 2630 (340)Data were described as frequency () for sex and mean (SD) for others

After 12 weeks of YMLI there was significant improve-ment in both cardinal and metabotrophic biomarkers of cel-lular aging compared to baseline values (Table 3) The meanlevels of 8-OH2dG and ROS were significantly lower andmean levels of TAC and telomerase activity were significantlyincreased (all values 119901 lt 005) The mean level of telomerelength was increased but this finding was not significant (119901 =0069)Themean levels of cortisol and IL-6 were significantlylower and mean levels of 120573-endorphin BDNF and sirtuin-1were significantly increased (all values 119901 lt 005)

A fewdifferenceswere noted in the gender subgroup anal-ysis Only the male subgroup showed a significant decreasein the levels of IL-6 and a more marked reduction in cortisollevels (males 119901 = 0001 females 119901 = 0036) After 12 weeks ofYMLI we also noted significantly reduced BMI in the studypopulation (119901 lt 001)

4 Discussion

The results of this study highlight the positive impact ofYMLI on biomarkers of cellular aging and in promotingcellular longevity through changes in both cardinal andmetabotrophic biomarkers The findings suggest that theimpact is mediated through improvement in genomic sta-bility telomere metabolism and balance of cellular oxidativestress well-regulated stress and inflammatory responses andincrease in neuroplasticity and nutrition sensing

Genomic stability is central to cellular longevity anddisease-free youthful healthy life and the findings from ourstudy suggest the reduction of genomic instability (decreasedlevels of 8-OH2dG) by YMLI Unhealthy social habits (smok-ing excess alcohol intake etc) sedentary lifestyle exposureto environmental pollutants and intake of processed andnutritionally depleted food have taken a toll on humanhealth with the onset of lifestyle diseases at a much youngerage [3ndash5] These environmental and lifestyle factors areresponsible for genomic instability [10] DNAdamage to boththe mitochondrial and nuclear genome from endogenous aswell as exogenous insults results in accumulation of geneticaberrations and genome hypermutability [8ndash10]

This is mainly due to aberrant DNA damage response(DDR) pathway which is essential for DNA repair and formonitoring genomic integrity Deficient DNA repair triggerssystemic effects to promote pathological aging [10] Thereduction of DNA damage by YMLI suggests the potentialof yoga in activating the DDR pathway to repair genomicdamage and improve genomic stability and changes inmetabotrophic factors seen in the study may be associatedwith these benefits

Maintaining telomere length through regulation oftelomere metabolism contributes to genomic stability andthe reduction in telomere attrition (increase in telomere

Oxidative Medicine and Cellular Longevity 5

Table 3 Change in outcomes in apparently healthy sedentary subjects participating in a Yoga- and Meditation-based lifestyle intervention(119899 = 94)

Characteristics Baseline 12 wksChange from baseline to

12wks(diff 95 CI)

Effect sizelowast p value

Primary endpoints cardinal biomarkersof cellular agingOxidative stress

ROS (RLUmin104 neutrophils) 1215069 plusmn 88 102081 plusmn 79 1943 (164 2245) 07 lt00001TAC (mmol Trolox equivL) 594 plusmn 152 74 plusmn 21 minus116 (minus19 minus041) 04 lt0001

DNA damage8OH2dG (pgmL) 102623 plusmn 630 79098 plusmn 400 2353 (7273 3978) 022 lt001

Telomere attritionTelomerase activity (IUcell) 189 plusmn 142 294 plusmn 22 minus105 (minus168 minus041) 03 lt0001Telomere length (IUcell) 236 plusmn 16 244 plusmn 14 minus008 (minus061 045) 002 0069

Secondary endpoints biomarkersassociated with cellular aging

Cortisol (ngmL) 11883plusmn5050 9632 plusmn 386 2251 (76 3742) 03 lt001Interleukin (IL6) (pgmL) 316 plusmn 242 194 plusmn 23 122 (047 197) 03 lt0001120573-Endorphins (ngmL) 62 plusmn 35 82 plusmn 42 minus2 (minus322 minus077) 03 lt0001BDNF (ngmL) 197 plusmn 675 371 plusmn 56 minus174 (minus1948 minus1532) 07 lt00001Sirtuin (ngmL) 2669 plusmn 1042 4064 plusmn 116 minus1395 (minus2341 minus449) 05 lt001

BMI (kgm2) 2630 plusmn 340 2364 plusmn 355 266 (056 312) 04 lt001lowastEffect size was calculated by dividing change by standard deviation at baseline of the specific outcome and interpreted using Cohenrsquos d (small effect 02 to03 medium effect 05 and large effect 08)

length and telomerase activity levels) shown by our studyafter YMLI suggests the potential for yoga in telomeremetabolism and cellular longevity Telomeres which serve asa biological clock are highly conserved hexameric repeatsand maintaining their length is vital for cellular longevityTelomerase is an important regulator of telomere length andaccurate regulation of its activity and a correct telomere-telomerase interaction is important to precisely safeguardtelomere length and prevent telomere attrition [44] ODDis prominent among the factors that can adversely affecttelomere length [45] Rapid telomere attrition due to ODDis associated with senescence and related disease conditions[46 47] Improved telomere metabolism after YMLI seen inthe study may contribute to genomic stability More researchis needed to explore the mechanisms of how yoga andmeditation can positively modify telomere metabolism

Our study suggests an improvement in maintenance ofbalance in cellular oxidative stress (decrease in ROS andincrease in TAC) caused by YMLI Supraphysiological ROSlevels are due to endogenous and exogenous factors likesmoking excess alcohol consumption exposure to elec-tromagnetic radiation infection xenobiotic exposure andpsychological stress [48] Even the levels of ROS belowphysiological limits are deleterious to normal cellular func-tion and maintaining OS at physiological levels is importantfor cellular longevity Increased OS causes damage to allmolecules including damage to DNA and telomeres Italso affects signal transduction and gene transcription bycausing genome-wide hypomethylation [49] and thus causes

changes in the epigenome Regulation of cellular oxidativestress within physiological limits after YMLI suggests thepotential of this intervention in protecting cells from OS-induced DNA damage and telomere attrition and in revers-ing epigenetic changes which are accumulated due to anunhealthy lifestyle and adverse environmental conditionsOther studies [50] support these findings and have shownreducedOSupregulation of telomerase activity anddecreasedODD after YMLI To combat OS people use antioxidantswithout monitoring ROS levels resulting in reductive stress[51] unlike in YMLI which regulates ROS levels so that noredox-sensitive physiological functions are impaired

Modern lifestyle and associated psychological stress havecomplex interactions with habits environmental conditionsandmedical interventions to cause accelerated cellular agingwhich adversely affect our mental physical and reproductivefitness [3ndash5] Improved cellular longevity after YMLI sug-gests the potential role of yoga in promoting this fitnessWhile psychological stress has a major effect on the mindcontributing to an increased prevalence of neuropsychiatricdisorders including depression abnormal fat accumulationis a major somatic manifestation contributing to increasedprevalence of metabolic syndrome and all the diseases thatcome under this umbrella including obesity DM and CVD[52] Other peripheral manifestations of unhealthy modernlifestyle include aging of gonads leading to infertility [53]and recurrent pregnancy loss Previous studies have demon-strated the clinical benefits of yoga and meditation in allthese medical conditions [35] Dada et al have shown that

6 Oxidative Medicine and Cellular Longevity

YMLI can reduce testicular aging and result in significantupregulation in telomerase activity and decline in seminalOS and ODD [8] The ongoing studies in our laboratory onthe impact of yoga and meditation have provided significantevidence for the reversal of cellular aging in subjects proneto accelerated aging due to depression Microarray (Agilent8 times 60k Microarray kit) and analysis of gene expression pre-and post-YMLI showed decreased IL6 IL10 and MAP10 andincreased IL2 and IL4 [8 54 55] Improved cellular longevityseen in our study after YMLI suggests that changes in bothcardinal andmetabotrophic biomarkers of cellular agingmaybe amechanism for preventing chronic lifestyle diseases Ourstudy suggests that the changes in metabotrophic factorswhich include increase in levels of 120573-endorphin BDNF andsirtuin-1 and decrease in levels of cortisol and IL-6 andthe cellular processes involving them may have importantroles in the reversal of cellular aging and improving cellularlongevity after YMLI

Improvements in stress and inflammatory response in ourstudy after YMLI may be mediated by changes in cortisol120573-endorphin IL-6 and other factors with regulation bychanges in the brain through the hypothalamic-pituitary-adrenal (HPA) axis The response may involve regulation ofadaptive pathways including integrated stress response (ISR)[18] that activates eukaryotic translation initiation factor 2alpha (eIF2120572) that promote cellular recovery driving signal-ing toward cell survival and longevityThe response may leadto decreased OS and a reversal of the senescent secretoryphenotype of cells including cells in the brain adipose tissueendothelium and gonads Changes in secretory phenotypeinclude decreased IL-6 [56] increased BDNF and sirtuin-1[57] These regulated factors may lead to balance in OS andcellular longevity and contribute to tissue revival throughoutthe body from neuroplasticity in CNS to gonads vessels andmuscles in the periphery Secretory phenotype from somaticcells provides regulatory feedback to brain [58] whichcompletes the vicious cycle of regulation between mind andbody Neurodegeneration is associated with the pathogenesisof several neuropsychiatric conditions and neuroplasticityhas a central role in their management and for vitalityIncreased BDNF sirtuin-1 and 120573-endorphin and decreasedcortisol each decrease cellular aging in brain decrease neu-rodegeneration and increase neuroplasticity [23] Increasedcellular longevity and increased neuroplasticity may be amechanism for alteration of gray matter volume in differentregions of the cerebral cortex [59] increased mindfulness[60] and several other complex processes [55 61] involvedin reduction of stress and depression after yoga and medi-tation Regulated mind-body communications may lead tominimization of subclinical inflammation and activation ofnutrition and energy-sensing pathways promoting longevitywhere a decrease in IL-6 and an increase in sirtuin-1 play aprominent role respectively Previous studies have demon-strated an increase in sirtuin-1 levels after interventions withcaloric restriction [62] Our study is the first to document anincrease in sirtuin-1 levels independent of caloric restrictionafter practicing yoga These improved processes may resultin delaying onset and slowing down progression of diseasesassociated with accelerated cellular aging

The impact of the intervention in both genders wasassessed separately sincemen andwomen respond differentlyto day-to-day stress [63] Interestingly the gender subgroupanalysis showed that reductions in cortisol and IL6 levelswere more pronounced in male than in female subjectsNo significant gender differences were seen in the otherbiomarkers Phase of the menstrual cycle should be takeninto consideration since some biomarker levels are knownto vary with different phases of the menstrual cycle [64 65]Our study showed a significant decrease in BMI in apparentlyhealthy subjects which came into the normal range (2364 plusmn355) from a baseline overweight range (2630 plusmn 340) Whilethe latest research [66] suggests people with a mean BMI of27 who are overweight by the current classification of obesityare likely to survive longest in a Western population similardata is not available for the Indian populationTherefore ourfindings need to be interpreted cautiously

Stratification of cases was not done in this study to do asubgroup analysis due to the small sample size

Lifestyle is an integrated entity and an intervention likeYMLI that has an overall positive influence on our healthappearsmost useful versus changing only one aspect at a timeas is seen by the action of certain drugs Yoga is holistic anda mind-body medicine and is more beneficial and advan-tageous than individual interventions like physical exercisecaloric restriction and antioxidantsThe practice of yoga andphysical exercise are different entities the former results inenergy conservation with economy of energy expenditure formental and physical benefits and the later results in energyexpendituremore for physical exertions andmetabolic needsas is evident from a study that showed exercise causeserratic changes in biomarkers and results in OS [67] whilemeditation brings about uniform biomarker and behavioralchanges and improvement in cognition and decreaseOS [68]Therapeutic antioxidants can only decrease ROS rather thanregulating it and may paradoxically shorten lifespan [69]due to an imbalance in ROS-mediated immune responses[70] YMLI regulates ROS rather than simply lowering themby balanced stress-related processes and appropriate geneexpression [71] The only limitation of our study is that itis a single-arm proof-of-concept study and did not includecontrols It is important to adopt a lifestyle that slows thedecline in health by reversing or delaying accelerated agingdue to unhealthy lifestyles The biomarkers of cellular agingcan form the basis for determining the risk of chronic lifestylediseases and the efficacy and usefulness of interventions todecrease disease risk Hence the findings from this studyare supportive of YMLI as having significant clinical utilityespecially in the prevention of and management of complexmultifactorial diseases and reducing the rate of functionaldecline with aging

5 Conclusion

Though we cannot change our biology or chronological agewe can definitely reverseslow down the pace at which weage by adopting YMLI This is the first study to demonstrateimprovement in both cardinal and metabotrophic biomark-ers of cellular aging and longevity in an apparently healthy

Oxidative Medicine and Cellular Longevity 7

population after a yoga- and meditation-based lifestyle inter-vention Our health and the rate at which we age entirelydepends on our choices Making yoga and meditation anintegral part of our lifestylemay hold the key to delay aging oraging gracefully prevent the onset of multifactorial complexlifestyle diseases promote mental physical and reproductivehealth and prolong youthful healthy life

Conflicts of Interest

Theauthors declare there are no conflicts of interest regardingthe publication of this article

Acknowledgments

The authors are thankful to Amit Tomar and SudhirChoudary for yoga instructions and to all the subjectsenrolled in the study

References

[1] M Tolahunase R Sagar and R Dada ldquoImpact of yoga andmeditation on cellular aging in apparently healthy individu-als a prospective open-label single-arm exploratory studyrdquoOxidative Medicine and Cellular Longevity vol 2017 Article ID7928981 9 pages 2017

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Page 2: Erratum - Hindawi

2 Oxidative Medicine and Cellular Longevity

responsible for cellular dysfunction in the pathogenesis oflifestyle diseases [8ndash10] OS is the most important causeof DNA damage Although many different oxidative DNAdamage (ODD) products have been identified 8-OH2dG (8-hydroxy-21015840-deoxyguanosine) a highly mutagenic oxidativeDNA adduct has been the subject of intensive study and is adefinitive biomarker of DNA damage [11] Telomere attritionis due to altered telomere metabolism involving a decreasein telomerase enzyme activity and an increase in OS Itcontributes to genomic instability and is associatedwith agingand lifestyle diseases [12]

Oxidative stress an imbalance between prooxidants andantioxidant defense mechanisms becomes pathological atboth extremes of the physiological range needed for normalcellular functions It is involved in the pathogenesis of com-plex lifestyle and chronic diseases [13] including depression[14] obesity [15] and infertility [16 17] the leading publichealth problems

Several metabotrophic blood biomarkers influencing cel-lular aging include biomarkers of stress and inflamma-tory response neuroplasticity and longevity Sustained stressresponses due to chronic stress stimuli cause constantlyincreased cortisol levels [18] which lead to systemic tissueabnormalities like increased adiposity and neurodegener-ation The level of stress responsiveness (cortisol levels)can be a biomarker for predicting susceptibility to lifestylediseases [19] Accelerated aging is characterized by a chroniclow-grade inflammation (ldquoinflammagingrdquo) Inflammaging isa highly significant risk factor for most chronic lifestylediseases [20] and is a potential modifiable target [21] IL-6is the most prominent cytokine in inflammaging and is botha marker of inflammatory status and a hallmark of chronicmorbidity [22] Impaired neuroplasticity due to acceleratedaging can have negative influence across the entire lifespan[23] BDNF is amajor regulator of neuroplasticity [24] whichmay be increased in specific regions of the brain by variousinterventions [25] Health span and longevity are influencedby several factors Sirtuin-1 (SIRT1) a histone deacetylase(HDAC) is prominent among them and recently has becomea target for various interventions [26] It systemically influ-ences nutrition and energy metabolism and centrally has arole in circadian rhythm survival against stress [27] andneuronal plasticity [28]

A variety of interventions have been studied [29 30] todetermine their influence on preventing lifestyle diseases andpromoting health and longevityThey include treatments tar-geting specific hallmarks of aging namely physical exercise[31] nutrition caloric restriction [32] and antioxidants [33]However no single intervention is shown to be an effectivepreventive and therapeutic strategy for modern complexlifestyle diseases and to provide comprehensive benefits fordelaying or reversing accelerated aging Therefore furtherresearch is needed to find optimum interventions for pop-ulation at risk of lifestyle diseases Yoga is an emergingintegrative health discipline which can positively modulatemind and body [34] and has been shown to improve theclinical profile of patients with various pathologies [35]including depression obesity hypertension asthma type IIdiabetes and cancerHowever recent reviews on yoga suggest

that potential underlying mechanisms need to be furtherexplored [36] Studies on biomarkers of disease and health inyoga-based interventions are limited and they have only high-lighted diabetic and lipid profiles [37 38] stress and inflam-matory markers [39 40] and neuroimaging correlates [41]in populations with specific medical conditions Evidence islacking regarding the efficacy of yoga lasting a short durationof 3 to 12 weeks in improving the biomarkers of cellular agingin apparently healthy people Thus the present study wasdesigned to evaluate the impact of a yoga- and meditation-based lifestyle intervention (YMLI) on cellular aging andlongevity by analyzing cardinal and metabotrophic biomark-ers in the peripheral blood of apparently healthy subjects

2 Materials and Methods

21 Study Design and Participants Ninety-six apparentlyhealthy people were enrolled in this 12-week prospectiveopen-label single-arm exploratory study from August 2015to May 2016 designed to explore the impact of YMLI oncellular aging The key inclusion criteria were male or femaleaged 30ndash65 years and leading an unhealthy modern lifestyleThe key exclusion criteria were inability to perform the yogicexercises due to any physical challenges and those with recentchanges in lifestyle during the last 3 months The study wasinitiated after ethical clearance (ESCT-37022-07-2015) andthe registration of the trial with the Clinical Trial Registry ofIndia (CTRI REF201409007532)

22 Procedure

221 Yoga- and Meditation-Based Lifestyle Intervention(YMLI) Eligible subjects were enrolled in the study afterscreening and baseline characteristics were recorded Par-ticipants underwent a 12-week pretested YMLI programcomprising theory and practice sessions [42 43] YMLI isdesigned to be an integrative health strategy incorporatingthe classic components of yoga including asanas (physi-cal postures) pranayama (breathing exercises) and dhayna(meditation) which are derived fromamix ofHatha yoga andRaja yogaThe YMLI for the current study was suitably mod-ified for apparently healthy subjects YMLI program includedsessions five days per week for 12 weeks For the first twoweeks the sessions were held at the integrated health clinic(IHC) AIIMS New Delhi and taught by registered spe-cialized yoga instructors (educational qualifications includeBachelor ofNaturopathy andYoga Sciences and PGDiplomain YogaTherapy) The remaining 10 weeks were home basedMonitoring of compliance of the home-based YMLI wasthrough maintenance of a diary and telephonic contact Thedetails of the activities in a day during the YMLI programare given in Table 1 Each session in YMLI included a set ofasanas pranayama and dhayna for approximately 90 min-utes This was followed by an interactive lecture (only duringthe first two weeks of YMLI at IHC) on lifestyle lifestylediseases and importance of their prevention for 30 minutes

222 Laboratory Procedures During this 12-week study theparticipants were evaluated for various biomarkers on day

Oxidative Medicine and Cellular Longevity 3

Table 1 Details of activities in a day of Yoga- and Meditation-based Lifestyle Intervention (YMLI) program

S No Practice to be done Duration(1) Session preparation instructions 5min

(2) Prayer 3minLoosening practices (warm-up) 5min

(3) Asanas (Postures)

SupineShavasana 2min

Uttanpadasana 2minPawanmuktasana 2min

ProneMakarasana 2minBhujangasana 2minSalabhasana 2min

SittingVakrasana 2min

Ardha-Matsyendrasana 2minVajrasana 2min

StandingTadasana 2min

Vrikshasana 2minArdhachakrasana 2min

(4) Relaxation Shavasana 5min

(5) Pranayama (Breathing Exercises)

Nadishodhana

20minBhramriShitkariShitali

Brahmamudra(6) Aumkar recitation 3min(7) Dhyana (Meditation) 20min(8) Shanti mantra 5min

(9)Interactive session (first 2 weeks only atIntegrated Health Clinic AIIMS New

Delhi)30min

Total 120min

0 and week 12 Fasting venous blood samples (5mL) werecollected and divided into two parts One part was allowedto clot and the serum was separated within 30minutes andthe other part was transferred to heparinizedEDTA vialsand was centrifuged at 2000119892 for 15 minutes at 4∘C Bothserum and plasma were stored at minus80∘C until analyzed ROSdetection was done by chemiluminescence assay (Bertholddetection luminometer USA) Peripheral blood leukocytetelomere lengthwasmeasured by qPCR and telomerase activ-ity was determined by using a telomerase assay kit (RocheSwitzerland) as per the manufacturerrsquos protocol 8-OH2dGwas estimated in white blood cell DNA (Caymanrsquos EIA kit)ELISA kits were used for levels of TAC (Cayman ChemicalAnn Arbor USA) cortisol (DRG Diagnostic Germany)120573-endorphin (Phoenix Pharmaceuticals Inc) IL-6 (Gen-Probe Diaclone Diagnostic France) BDNF (RaybiotechInc) and sirtuin-1 (Quayee Bio-Technology) Quality controlassays for biomarkers and validation were performed

223 Endpoints The primary endpoint was to assess thechange in levels of cardinal biomarkers of cellular aging frombaseline to week 12 The biomarkers included the following

8-OH2dG ROS and TAC (markers of OS and ODD) aswell as telomere length and telomerase activity (telomereattritionmarkers)The secondary endpoints were assessmentof metabotrophic blood biomarkers associated with cellularaging which included cortisol 120573-endorphin IL-6 BDNFand sirtuin-1 from baseline to week 12

23 Statistical Analysis Data were analyzed using SPSS 20(IBM Corp Armonk NY) Descriptive statistics are reportedas means and standard deviations Changes in outcome vari-ables were analyzed using paired-samples t-tests Exploratoryanalysis included comparisons for within gender subgroupsusing paired-sample t-tests Significance was accepted at 119901 lt005

3 Results

Theflowdiagramof participant details is provided in Figure 1Of 96 subjects 94 subjects were assessed for impact analysisTwo subjects were excluded from the analysis due to poorcompliance to the program Baseline sociodemographic char-acteristics are shown in Table 2

4 Oxidative Medicine and Cellular Longevity

Assessed for eligibility (n = 120)

Excluded (n = 24)

Not meeting inclusion criteria (n = 15)

Declined to participate (n = 9)

Enrolled (n = 96) to receive YLMI for

12 weeks

Analyzed (n = 94)

Dropped out from YMLI (n = 2)

Figure 1 Flow diagram of study participation

Table 2 Sociodemographic characteristics of participants

Variable ValuesAge (years) 4026 (1013)Sex

Female 52 (5532)Male 42 (4468)

Socioeconomic statusKuppuswamy socioeconomic status scale

Education 482 (124)Occupation 526 (238)Income 860 (274)Total 1868 (734)

BMI (kgm2) 2630 (340)Data were described as frequency () for sex and mean (SD) for others

After 12 weeks of YMLI there was significant improve-ment in both cardinal and metabotrophic biomarkers of cel-lular aging compared to baseline values (Table 3) The meanlevels of 8-OH2dG and ROS were significantly lower andmean levels of TAC and telomerase activity were significantlyincreased (all values 119901 lt 005) The mean level of telomerelength was increased but this finding was not significant (119901 =0069)Themean levels of cortisol and IL-6 were significantlylower and mean levels of 120573-endorphin BDNF and sirtuin-1were significantly increased (all values 119901 lt 005)

A fewdifferenceswere noted in the gender subgroup anal-ysis Only the male subgroup showed a significant decreasein the levels of IL-6 and a more marked reduction in cortisollevels (males 119901 = 0001 females 119901 = 0036) After 12 weeks ofYMLI we also noted significantly reduced BMI in the studypopulation (119901 lt 001)

4 Discussion

The results of this study highlight the positive impact ofYMLI on biomarkers of cellular aging and in promotingcellular longevity through changes in both cardinal andmetabotrophic biomarkers The findings suggest that theimpact is mediated through improvement in genomic sta-bility telomere metabolism and balance of cellular oxidativestress well-regulated stress and inflammatory responses andincrease in neuroplasticity and nutrition sensing

Genomic stability is central to cellular longevity anddisease-free youthful healthy life and the findings from ourstudy suggest the reduction of genomic instability (decreasedlevels of 8-OH2dG) by YMLI Unhealthy social habits (smok-ing excess alcohol intake etc) sedentary lifestyle exposureto environmental pollutants and intake of processed andnutritionally depleted food have taken a toll on humanhealth with the onset of lifestyle diseases at a much youngerage [3ndash5] These environmental and lifestyle factors areresponsible for genomic instability [10] DNAdamage to boththe mitochondrial and nuclear genome from endogenous aswell as exogenous insults results in accumulation of geneticaberrations and genome hypermutability [8ndash10]

This is mainly due to aberrant DNA damage response(DDR) pathway which is essential for DNA repair and formonitoring genomic integrity Deficient DNA repair triggerssystemic effects to promote pathological aging [10] Thereduction of DNA damage by YMLI suggests the potentialof yoga in activating the DDR pathway to repair genomicdamage and improve genomic stability and changes inmetabotrophic factors seen in the study may be associatedwith these benefits

Maintaining telomere length through regulation oftelomere metabolism contributes to genomic stability andthe reduction in telomere attrition (increase in telomere

Oxidative Medicine and Cellular Longevity 5

Table 3 Change in outcomes in apparently healthy sedentary subjects participating in a Yoga- and Meditation-based lifestyle intervention(119899 = 94)

Characteristics Baseline 12 wksChange from baseline to

12wks(diff 95 CI)

Effect sizelowast p value

Primary endpoints cardinal biomarkersof cellular agingOxidative stress

ROS (RLUmin104 neutrophils) 1215069 plusmn 88 102081 plusmn 79 1943 (164 2245) 07 lt00001TAC (mmol Trolox equivL) 594 plusmn 152 74 plusmn 21 minus116 (minus19 minus041) 04 lt0001

DNA damage8OH2dG (pgmL) 102623 plusmn 630 79098 plusmn 400 2353 (7273 3978) 022 lt001

Telomere attritionTelomerase activity (IUcell) 189 plusmn 142 294 plusmn 22 minus105 (minus168 minus041) 03 lt0001Telomere length (IUcell) 236 plusmn 16 244 plusmn 14 minus008 (minus061 045) 002 0069

Secondary endpoints biomarkersassociated with cellular aging

Cortisol (ngmL) 11883plusmn5050 9632 plusmn 386 2251 (76 3742) 03 lt001Interleukin (IL6) (pgmL) 316 plusmn 242 194 plusmn 23 122 (047 197) 03 lt0001120573-Endorphins (ngmL) 62 plusmn 35 82 plusmn 42 minus2 (minus322 minus077) 03 lt0001BDNF (ngmL) 197 plusmn 675 371 plusmn 56 minus174 (minus1948 minus1532) 07 lt00001Sirtuin (ngmL) 2669 plusmn 1042 4064 plusmn 116 minus1395 (minus2341 minus449) 05 lt001

BMI (kgm2) 2630 plusmn 340 2364 plusmn 355 266 (056 312) 04 lt001lowastEffect size was calculated by dividing change by standard deviation at baseline of the specific outcome and interpreted using Cohenrsquos d (small effect 02 to03 medium effect 05 and large effect 08)

length and telomerase activity levels) shown by our studyafter YMLI suggests the potential for yoga in telomeremetabolism and cellular longevity Telomeres which serve asa biological clock are highly conserved hexameric repeatsand maintaining their length is vital for cellular longevityTelomerase is an important regulator of telomere length andaccurate regulation of its activity and a correct telomere-telomerase interaction is important to precisely safeguardtelomere length and prevent telomere attrition [44] ODDis prominent among the factors that can adversely affecttelomere length [45] Rapid telomere attrition due to ODDis associated with senescence and related disease conditions[46 47] Improved telomere metabolism after YMLI seen inthe study may contribute to genomic stability More researchis needed to explore the mechanisms of how yoga andmeditation can positively modify telomere metabolism

Our study suggests an improvement in maintenance ofbalance in cellular oxidative stress (decrease in ROS andincrease in TAC) caused by YMLI Supraphysiological ROSlevels are due to endogenous and exogenous factors likesmoking excess alcohol consumption exposure to elec-tromagnetic radiation infection xenobiotic exposure andpsychological stress [48] Even the levels of ROS belowphysiological limits are deleterious to normal cellular func-tion and maintaining OS at physiological levels is importantfor cellular longevity Increased OS causes damage to allmolecules including damage to DNA and telomeres Italso affects signal transduction and gene transcription bycausing genome-wide hypomethylation [49] and thus causes

changes in the epigenome Regulation of cellular oxidativestress within physiological limits after YMLI suggests thepotential of this intervention in protecting cells from OS-induced DNA damage and telomere attrition and in revers-ing epigenetic changes which are accumulated due to anunhealthy lifestyle and adverse environmental conditionsOther studies [50] support these findings and have shownreducedOSupregulation of telomerase activity anddecreasedODD after YMLI To combat OS people use antioxidantswithout monitoring ROS levels resulting in reductive stress[51] unlike in YMLI which regulates ROS levels so that noredox-sensitive physiological functions are impaired

Modern lifestyle and associated psychological stress havecomplex interactions with habits environmental conditionsandmedical interventions to cause accelerated cellular agingwhich adversely affect our mental physical and reproductivefitness [3ndash5] Improved cellular longevity after YMLI sug-gests the potential role of yoga in promoting this fitnessWhile psychological stress has a major effect on the mindcontributing to an increased prevalence of neuropsychiatricdisorders including depression abnormal fat accumulationis a major somatic manifestation contributing to increasedprevalence of metabolic syndrome and all the diseases thatcome under this umbrella including obesity DM and CVD[52] Other peripheral manifestations of unhealthy modernlifestyle include aging of gonads leading to infertility [53]and recurrent pregnancy loss Previous studies have demon-strated the clinical benefits of yoga and meditation in allthese medical conditions [35] Dada et al have shown that

6 Oxidative Medicine and Cellular Longevity

YMLI can reduce testicular aging and result in significantupregulation in telomerase activity and decline in seminalOS and ODD [8] The ongoing studies in our laboratory onthe impact of yoga and meditation have provided significantevidence for the reversal of cellular aging in subjects proneto accelerated aging due to depression Microarray (Agilent8 times 60k Microarray kit) and analysis of gene expression pre-and post-YMLI showed decreased IL6 IL10 and MAP10 andincreased IL2 and IL4 [8 54 55] Improved cellular longevityseen in our study after YMLI suggests that changes in bothcardinal andmetabotrophic biomarkers of cellular agingmaybe amechanism for preventing chronic lifestyle diseases Ourstudy suggests that the changes in metabotrophic factorswhich include increase in levels of 120573-endorphin BDNF andsirtuin-1 and decrease in levels of cortisol and IL-6 andthe cellular processes involving them may have importantroles in the reversal of cellular aging and improving cellularlongevity after YMLI

Improvements in stress and inflammatory response in ourstudy after YMLI may be mediated by changes in cortisol120573-endorphin IL-6 and other factors with regulation bychanges in the brain through the hypothalamic-pituitary-adrenal (HPA) axis The response may involve regulation ofadaptive pathways including integrated stress response (ISR)[18] that activates eukaryotic translation initiation factor 2alpha (eIF2120572) that promote cellular recovery driving signal-ing toward cell survival and longevityThe response may leadto decreased OS and a reversal of the senescent secretoryphenotype of cells including cells in the brain adipose tissueendothelium and gonads Changes in secretory phenotypeinclude decreased IL-6 [56] increased BDNF and sirtuin-1[57] These regulated factors may lead to balance in OS andcellular longevity and contribute to tissue revival throughoutthe body from neuroplasticity in CNS to gonads vessels andmuscles in the periphery Secretory phenotype from somaticcells provides regulatory feedback to brain [58] whichcompletes the vicious cycle of regulation between mind andbody Neurodegeneration is associated with the pathogenesisof several neuropsychiatric conditions and neuroplasticityhas a central role in their management and for vitalityIncreased BDNF sirtuin-1 and 120573-endorphin and decreasedcortisol each decrease cellular aging in brain decrease neu-rodegeneration and increase neuroplasticity [23] Increasedcellular longevity and increased neuroplasticity may be amechanism for alteration of gray matter volume in differentregions of the cerebral cortex [59] increased mindfulness[60] and several other complex processes [55 61] involvedin reduction of stress and depression after yoga and medi-tation Regulated mind-body communications may lead tominimization of subclinical inflammation and activation ofnutrition and energy-sensing pathways promoting longevitywhere a decrease in IL-6 and an increase in sirtuin-1 play aprominent role respectively Previous studies have demon-strated an increase in sirtuin-1 levels after interventions withcaloric restriction [62] Our study is the first to document anincrease in sirtuin-1 levels independent of caloric restrictionafter practicing yoga These improved processes may resultin delaying onset and slowing down progression of diseasesassociated with accelerated cellular aging

The impact of the intervention in both genders wasassessed separately sincemen andwomen respond differentlyto day-to-day stress [63] Interestingly the gender subgroupanalysis showed that reductions in cortisol and IL6 levelswere more pronounced in male than in female subjectsNo significant gender differences were seen in the otherbiomarkers Phase of the menstrual cycle should be takeninto consideration since some biomarker levels are knownto vary with different phases of the menstrual cycle [64 65]Our study showed a significant decrease in BMI in apparentlyhealthy subjects which came into the normal range (2364 plusmn355) from a baseline overweight range (2630 plusmn 340) Whilethe latest research [66] suggests people with a mean BMI of27 who are overweight by the current classification of obesityare likely to survive longest in a Western population similardata is not available for the Indian populationTherefore ourfindings need to be interpreted cautiously

Stratification of cases was not done in this study to do asubgroup analysis due to the small sample size

Lifestyle is an integrated entity and an intervention likeYMLI that has an overall positive influence on our healthappearsmost useful versus changing only one aspect at a timeas is seen by the action of certain drugs Yoga is holistic anda mind-body medicine and is more beneficial and advan-tageous than individual interventions like physical exercisecaloric restriction and antioxidantsThe practice of yoga andphysical exercise are different entities the former results inenergy conservation with economy of energy expenditure formental and physical benefits and the later results in energyexpendituremore for physical exertions andmetabolic needsas is evident from a study that showed exercise causeserratic changes in biomarkers and results in OS [67] whilemeditation brings about uniform biomarker and behavioralchanges and improvement in cognition and decreaseOS [68]Therapeutic antioxidants can only decrease ROS rather thanregulating it and may paradoxically shorten lifespan [69]due to an imbalance in ROS-mediated immune responses[70] YMLI regulates ROS rather than simply lowering themby balanced stress-related processes and appropriate geneexpression [71] The only limitation of our study is that itis a single-arm proof-of-concept study and did not includecontrols It is important to adopt a lifestyle that slows thedecline in health by reversing or delaying accelerated agingdue to unhealthy lifestyles The biomarkers of cellular agingcan form the basis for determining the risk of chronic lifestylediseases and the efficacy and usefulness of interventions todecrease disease risk Hence the findings from this studyare supportive of YMLI as having significant clinical utilityespecially in the prevention of and management of complexmultifactorial diseases and reducing the rate of functionaldecline with aging

5 Conclusion

Though we cannot change our biology or chronological agewe can definitely reverseslow down the pace at which weage by adopting YMLI This is the first study to demonstrateimprovement in both cardinal and metabotrophic biomark-ers of cellular aging and longevity in an apparently healthy

Oxidative Medicine and Cellular Longevity 7

population after a yoga- and meditation-based lifestyle inter-vention Our health and the rate at which we age entirelydepends on our choices Making yoga and meditation anintegral part of our lifestylemay hold the key to delay aging oraging gracefully prevent the onset of multifactorial complexlifestyle diseases promote mental physical and reproductivehealth and prolong youthful healthy life

Conflicts of Interest

Theauthors declare there are no conflicts of interest regardingthe publication of this article

Acknowledgments

The authors are thankful to Amit Tomar and SudhirChoudary for yoga instructions and to all the subjectsenrolled in the study

References

[1] M Tolahunase R Sagar and R Dada ldquoImpact of yoga andmeditation on cellular aging in apparently healthy individu-als a prospective open-label single-arm exploratory studyrdquoOxidative Medicine and Cellular Longevity vol 2017 Article ID7928981 9 pages 2017

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

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MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

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BioMed Research International

OncologyJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 3: Erratum - Hindawi

Oxidative Medicine and Cellular Longevity 3

Table 1 Details of activities in a day of Yoga- and Meditation-based Lifestyle Intervention (YMLI) program

S No Practice to be done Duration(1) Session preparation instructions 5min

(2) Prayer 3minLoosening practices (warm-up) 5min

(3) Asanas (Postures)

SupineShavasana 2min

Uttanpadasana 2minPawanmuktasana 2min

ProneMakarasana 2minBhujangasana 2minSalabhasana 2min

SittingVakrasana 2min

Ardha-Matsyendrasana 2minVajrasana 2min

StandingTadasana 2min

Vrikshasana 2minArdhachakrasana 2min

(4) Relaxation Shavasana 5min

(5) Pranayama (Breathing Exercises)

Nadishodhana

20minBhramriShitkariShitali

Brahmamudra(6) Aumkar recitation 3min(7) Dhyana (Meditation) 20min(8) Shanti mantra 5min

(9)Interactive session (first 2 weeks only atIntegrated Health Clinic AIIMS New

Delhi)30min

Total 120min

0 and week 12 Fasting venous blood samples (5mL) werecollected and divided into two parts One part was allowedto clot and the serum was separated within 30minutes andthe other part was transferred to heparinizedEDTA vialsand was centrifuged at 2000119892 for 15 minutes at 4∘C Bothserum and plasma were stored at minus80∘C until analyzed ROSdetection was done by chemiluminescence assay (Bertholddetection luminometer USA) Peripheral blood leukocytetelomere lengthwasmeasured by qPCR and telomerase activ-ity was determined by using a telomerase assay kit (RocheSwitzerland) as per the manufacturerrsquos protocol 8-OH2dGwas estimated in white blood cell DNA (Caymanrsquos EIA kit)ELISA kits were used for levels of TAC (Cayman ChemicalAnn Arbor USA) cortisol (DRG Diagnostic Germany)120573-endorphin (Phoenix Pharmaceuticals Inc) IL-6 (Gen-Probe Diaclone Diagnostic France) BDNF (RaybiotechInc) and sirtuin-1 (Quayee Bio-Technology) Quality controlassays for biomarkers and validation were performed

223 Endpoints The primary endpoint was to assess thechange in levels of cardinal biomarkers of cellular aging frombaseline to week 12 The biomarkers included the following

8-OH2dG ROS and TAC (markers of OS and ODD) aswell as telomere length and telomerase activity (telomereattritionmarkers)The secondary endpoints were assessmentof metabotrophic blood biomarkers associated with cellularaging which included cortisol 120573-endorphin IL-6 BDNFand sirtuin-1 from baseline to week 12

23 Statistical Analysis Data were analyzed using SPSS 20(IBM Corp Armonk NY) Descriptive statistics are reportedas means and standard deviations Changes in outcome vari-ables were analyzed using paired-samples t-tests Exploratoryanalysis included comparisons for within gender subgroupsusing paired-sample t-tests Significance was accepted at 119901 lt005

3 Results

Theflowdiagramof participant details is provided in Figure 1Of 96 subjects 94 subjects were assessed for impact analysisTwo subjects were excluded from the analysis due to poorcompliance to the program Baseline sociodemographic char-acteristics are shown in Table 2

4 Oxidative Medicine and Cellular Longevity

Assessed for eligibility (n = 120)

Excluded (n = 24)

Not meeting inclusion criteria (n = 15)

Declined to participate (n = 9)

Enrolled (n = 96) to receive YLMI for

12 weeks

Analyzed (n = 94)

Dropped out from YMLI (n = 2)

Figure 1 Flow diagram of study participation

Table 2 Sociodemographic characteristics of participants

Variable ValuesAge (years) 4026 (1013)Sex

Female 52 (5532)Male 42 (4468)

Socioeconomic statusKuppuswamy socioeconomic status scale

Education 482 (124)Occupation 526 (238)Income 860 (274)Total 1868 (734)

BMI (kgm2) 2630 (340)Data were described as frequency () for sex and mean (SD) for others

After 12 weeks of YMLI there was significant improve-ment in both cardinal and metabotrophic biomarkers of cel-lular aging compared to baseline values (Table 3) The meanlevels of 8-OH2dG and ROS were significantly lower andmean levels of TAC and telomerase activity were significantlyincreased (all values 119901 lt 005) The mean level of telomerelength was increased but this finding was not significant (119901 =0069)Themean levels of cortisol and IL-6 were significantlylower and mean levels of 120573-endorphin BDNF and sirtuin-1were significantly increased (all values 119901 lt 005)

A fewdifferenceswere noted in the gender subgroup anal-ysis Only the male subgroup showed a significant decreasein the levels of IL-6 and a more marked reduction in cortisollevels (males 119901 = 0001 females 119901 = 0036) After 12 weeks ofYMLI we also noted significantly reduced BMI in the studypopulation (119901 lt 001)

4 Discussion

The results of this study highlight the positive impact ofYMLI on biomarkers of cellular aging and in promotingcellular longevity through changes in both cardinal andmetabotrophic biomarkers The findings suggest that theimpact is mediated through improvement in genomic sta-bility telomere metabolism and balance of cellular oxidativestress well-regulated stress and inflammatory responses andincrease in neuroplasticity and nutrition sensing

Genomic stability is central to cellular longevity anddisease-free youthful healthy life and the findings from ourstudy suggest the reduction of genomic instability (decreasedlevels of 8-OH2dG) by YMLI Unhealthy social habits (smok-ing excess alcohol intake etc) sedentary lifestyle exposureto environmental pollutants and intake of processed andnutritionally depleted food have taken a toll on humanhealth with the onset of lifestyle diseases at a much youngerage [3ndash5] These environmental and lifestyle factors areresponsible for genomic instability [10] DNAdamage to boththe mitochondrial and nuclear genome from endogenous aswell as exogenous insults results in accumulation of geneticaberrations and genome hypermutability [8ndash10]

This is mainly due to aberrant DNA damage response(DDR) pathway which is essential for DNA repair and formonitoring genomic integrity Deficient DNA repair triggerssystemic effects to promote pathological aging [10] Thereduction of DNA damage by YMLI suggests the potentialof yoga in activating the DDR pathway to repair genomicdamage and improve genomic stability and changes inmetabotrophic factors seen in the study may be associatedwith these benefits

Maintaining telomere length through regulation oftelomere metabolism contributes to genomic stability andthe reduction in telomere attrition (increase in telomere

Oxidative Medicine and Cellular Longevity 5

Table 3 Change in outcomes in apparently healthy sedentary subjects participating in a Yoga- and Meditation-based lifestyle intervention(119899 = 94)

Characteristics Baseline 12 wksChange from baseline to

12wks(diff 95 CI)

Effect sizelowast p value

Primary endpoints cardinal biomarkersof cellular agingOxidative stress

ROS (RLUmin104 neutrophils) 1215069 plusmn 88 102081 plusmn 79 1943 (164 2245) 07 lt00001TAC (mmol Trolox equivL) 594 plusmn 152 74 plusmn 21 minus116 (minus19 minus041) 04 lt0001

DNA damage8OH2dG (pgmL) 102623 plusmn 630 79098 plusmn 400 2353 (7273 3978) 022 lt001

Telomere attritionTelomerase activity (IUcell) 189 plusmn 142 294 plusmn 22 minus105 (minus168 minus041) 03 lt0001Telomere length (IUcell) 236 plusmn 16 244 plusmn 14 minus008 (minus061 045) 002 0069

Secondary endpoints biomarkersassociated with cellular aging

Cortisol (ngmL) 11883plusmn5050 9632 plusmn 386 2251 (76 3742) 03 lt001Interleukin (IL6) (pgmL) 316 plusmn 242 194 plusmn 23 122 (047 197) 03 lt0001120573-Endorphins (ngmL) 62 plusmn 35 82 plusmn 42 minus2 (minus322 minus077) 03 lt0001BDNF (ngmL) 197 plusmn 675 371 plusmn 56 minus174 (minus1948 minus1532) 07 lt00001Sirtuin (ngmL) 2669 plusmn 1042 4064 plusmn 116 minus1395 (minus2341 minus449) 05 lt001

BMI (kgm2) 2630 plusmn 340 2364 plusmn 355 266 (056 312) 04 lt001lowastEffect size was calculated by dividing change by standard deviation at baseline of the specific outcome and interpreted using Cohenrsquos d (small effect 02 to03 medium effect 05 and large effect 08)

length and telomerase activity levels) shown by our studyafter YMLI suggests the potential for yoga in telomeremetabolism and cellular longevity Telomeres which serve asa biological clock are highly conserved hexameric repeatsand maintaining their length is vital for cellular longevityTelomerase is an important regulator of telomere length andaccurate regulation of its activity and a correct telomere-telomerase interaction is important to precisely safeguardtelomere length and prevent telomere attrition [44] ODDis prominent among the factors that can adversely affecttelomere length [45] Rapid telomere attrition due to ODDis associated with senescence and related disease conditions[46 47] Improved telomere metabolism after YMLI seen inthe study may contribute to genomic stability More researchis needed to explore the mechanisms of how yoga andmeditation can positively modify telomere metabolism

Our study suggests an improvement in maintenance ofbalance in cellular oxidative stress (decrease in ROS andincrease in TAC) caused by YMLI Supraphysiological ROSlevels are due to endogenous and exogenous factors likesmoking excess alcohol consumption exposure to elec-tromagnetic radiation infection xenobiotic exposure andpsychological stress [48] Even the levels of ROS belowphysiological limits are deleterious to normal cellular func-tion and maintaining OS at physiological levels is importantfor cellular longevity Increased OS causes damage to allmolecules including damage to DNA and telomeres Italso affects signal transduction and gene transcription bycausing genome-wide hypomethylation [49] and thus causes

changes in the epigenome Regulation of cellular oxidativestress within physiological limits after YMLI suggests thepotential of this intervention in protecting cells from OS-induced DNA damage and telomere attrition and in revers-ing epigenetic changes which are accumulated due to anunhealthy lifestyle and adverse environmental conditionsOther studies [50] support these findings and have shownreducedOSupregulation of telomerase activity anddecreasedODD after YMLI To combat OS people use antioxidantswithout monitoring ROS levels resulting in reductive stress[51] unlike in YMLI which regulates ROS levels so that noredox-sensitive physiological functions are impaired

Modern lifestyle and associated psychological stress havecomplex interactions with habits environmental conditionsandmedical interventions to cause accelerated cellular agingwhich adversely affect our mental physical and reproductivefitness [3ndash5] Improved cellular longevity after YMLI sug-gests the potential role of yoga in promoting this fitnessWhile psychological stress has a major effect on the mindcontributing to an increased prevalence of neuropsychiatricdisorders including depression abnormal fat accumulationis a major somatic manifestation contributing to increasedprevalence of metabolic syndrome and all the diseases thatcome under this umbrella including obesity DM and CVD[52] Other peripheral manifestations of unhealthy modernlifestyle include aging of gonads leading to infertility [53]and recurrent pregnancy loss Previous studies have demon-strated the clinical benefits of yoga and meditation in allthese medical conditions [35] Dada et al have shown that

6 Oxidative Medicine and Cellular Longevity

YMLI can reduce testicular aging and result in significantupregulation in telomerase activity and decline in seminalOS and ODD [8] The ongoing studies in our laboratory onthe impact of yoga and meditation have provided significantevidence for the reversal of cellular aging in subjects proneto accelerated aging due to depression Microarray (Agilent8 times 60k Microarray kit) and analysis of gene expression pre-and post-YMLI showed decreased IL6 IL10 and MAP10 andincreased IL2 and IL4 [8 54 55] Improved cellular longevityseen in our study after YMLI suggests that changes in bothcardinal andmetabotrophic biomarkers of cellular agingmaybe amechanism for preventing chronic lifestyle diseases Ourstudy suggests that the changes in metabotrophic factorswhich include increase in levels of 120573-endorphin BDNF andsirtuin-1 and decrease in levels of cortisol and IL-6 andthe cellular processes involving them may have importantroles in the reversal of cellular aging and improving cellularlongevity after YMLI

Improvements in stress and inflammatory response in ourstudy after YMLI may be mediated by changes in cortisol120573-endorphin IL-6 and other factors with regulation bychanges in the brain through the hypothalamic-pituitary-adrenal (HPA) axis The response may involve regulation ofadaptive pathways including integrated stress response (ISR)[18] that activates eukaryotic translation initiation factor 2alpha (eIF2120572) that promote cellular recovery driving signal-ing toward cell survival and longevityThe response may leadto decreased OS and a reversal of the senescent secretoryphenotype of cells including cells in the brain adipose tissueendothelium and gonads Changes in secretory phenotypeinclude decreased IL-6 [56] increased BDNF and sirtuin-1[57] These regulated factors may lead to balance in OS andcellular longevity and contribute to tissue revival throughoutthe body from neuroplasticity in CNS to gonads vessels andmuscles in the periphery Secretory phenotype from somaticcells provides regulatory feedback to brain [58] whichcompletes the vicious cycle of regulation between mind andbody Neurodegeneration is associated with the pathogenesisof several neuropsychiatric conditions and neuroplasticityhas a central role in their management and for vitalityIncreased BDNF sirtuin-1 and 120573-endorphin and decreasedcortisol each decrease cellular aging in brain decrease neu-rodegeneration and increase neuroplasticity [23] Increasedcellular longevity and increased neuroplasticity may be amechanism for alteration of gray matter volume in differentregions of the cerebral cortex [59] increased mindfulness[60] and several other complex processes [55 61] involvedin reduction of stress and depression after yoga and medi-tation Regulated mind-body communications may lead tominimization of subclinical inflammation and activation ofnutrition and energy-sensing pathways promoting longevitywhere a decrease in IL-6 and an increase in sirtuin-1 play aprominent role respectively Previous studies have demon-strated an increase in sirtuin-1 levels after interventions withcaloric restriction [62] Our study is the first to document anincrease in sirtuin-1 levels independent of caloric restrictionafter practicing yoga These improved processes may resultin delaying onset and slowing down progression of diseasesassociated with accelerated cellular aging

The impact of the intervention in both genders wasassessed separately sincemen andwomen respond differentlyto day-to-day stress [63] Interestingly the gender subgroupanalysis showed that reductions in cortisol and IL6 levelswere more pronounced in male than in female subjectsNo significant gender differences were seen in the otherbiomarkers Phase of the menstrual cycle should be takeninto consideration since some biomarker levels are knownto vary with different phases of the menstrual cycle [64 65]Our study showed a significant decrease in BMI in apparentlyhealthy subjects which came into the normal range (2364 plusmn355) from a baseline overweight range (2630 plusmn 340) Whilethe latest research [66] suggests people with a mean BMI of27 who are overweight by the current classification of obesityare likely to survive longest in a Western population similardata is not available for the Indian populationTherefore ourfindings need to be interpreted cautiously

Stratification of cases was not done in this study to do asubgroup analysis due to the small sample size

Lifestyle is an integrated entity and an intervention likeYMLI that has an overall positive influence on our healthappearsmost useful versus changing only one aspect at a timeas is seen by the action of certain drugs Yoga is holistic anda mind-body medicine and is more beneficial and advan-tageous than individual interventions like physical exercisecaloric restriction and antioxidantsThe practice of yoga andphysical exercise are different entities the former results inenergy conservation with economy of energy expenditure formental and physical benefits and the later results in energyexpendituremore for physical exertions andmetabolic needsas is evident from a study that showed exercise causeserratic changes in biomarkers and results in OS [67] whilemeditation brings about uniform biomarker and behavioralchanges and improvement in cognition and decreaseOS [68]Therapeutic antioxidants can only decrease ROS rather thanregulating it and may paradoxically shorten lifespan [69]due to an imbalance in ROS-mediated immune responses[70] YMLI regulates ROS rather than simply lowering themby balanced stress-related processes and appropriate geneexpression [71] The only limitation of our study is that itis a single-arm proof-of-concept study and did not includecontrols It is important to adopt a lifestyle that slows thedecline in health by reversing or delaying accelerated agingdue to unhealthy lifestyles The biomarkers of cellular agingcan form the basis for determining the risk of chronic lifestylediseases and the efficacy and usefulness of interventions todecrease disease risk Hence the findings from this studyare supportive of YMLI as having significant clinical utilityespecially in the prevention of and management of complexmultifactorial diseases and reducing the rate of functionaldecline with aging

5 Conclusion

Though we cannot change our biology or chronological agewe can definitely reverseslow down the pace at which weage by adopting YMLI This is the first study to demonstrateimprovement in both cardinal and metabotrophic biomark-ers of cellular aging and longevity in an apparently healthy

Oxidative Medicine and Cellular Longevity 7

population after a yoga- and meditation-based lifestyle inter-vention Our health and the rate at which we age entirelydepends on our choices Making yoga and meditation anintegral part of our lifestylemay hold the key to delay aging oraging gracefully prevent the onset of multifactorial complexlifestyle diseases promote mental physical and reproductivehealth and prolong youthful healthy life

Conflicts of Interest

Theauthors declare there are no conflicts of interest regardingthe publication of this article

Acknowledgments

The authors are thankful to Amit Tomar and SudhirChoudary for yoga instructions and to all the subjectsenrolled in the study

References

[1] M Tolahunase R Sagar and R Dada ldquoImpact of yoga andmeditation on cellular aging in apparently healthy individu-als a prospective open-label single-arm exploratory studyrdquoOxidative Medicine and Cellular Longevity vol 2017 Article ID7928981 9 pages 2017

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 4: Erratum - Hindawi

4 Oxidative Medicine and Cellular Longevity

Assessed for eligibility (n = 120)

Excluded (n = 24)

Not meeting inclusion criteria (n = 15)

Declined to participate (n = 9)

Enrolled (n = 96) to receive YLMI for

12 weeks

Analyzed (n = 94)

Dropped out from YMLI (n = 2)

Figure 1 Flow diagram of study participation

Table 2 Sociodemographic characteristics of participants

Variable ValuesAge (years) 4026 (1013)Sex

Female 52 (5532)Male 42 (4468)

Socioeconomic statusKuppuswamy socioeconomic status scale

Education 482 (124)Occupation 526 (238)Income 860 (274)Total 1868 (734)

BMI (kgm2) 2630 (340)Data were described as frequency () for sex and mean (SD) for others

After 12 weeks of YMLI there was significant improve-ment in both cardinal and metabotrophic biomarkers of cel-lular aging compared to baseline values (Table 3) The meanlevels of 8-OH2dG and ROS were significantly lower andmean levels of TAC and telomerase activity were significantlyincreased (all values 119901 lt 005) The mean level of telomerelength was increased but this finding was not significant (119901 =0069)Themean levels of cortisol and IL-6 were significantlylower and mean levels of 120573-endorphin BDNF and sirtuin-1were significantly increased (all values 119901 lt 005)

A fewdifferenceswere noted in the gender subgroup anal-ysis Only the male subgroup showed a significant decreasein the levels of IL-6 and a more marked reduction in cortisollevels (males 119901 = 0001 females 119901 = 0036) After 12 weeks ofYMLI we also noted significantly reduced BMI in the studypopulation (119901 lt 001)

4 Discussion

The results of this study highlight the positive impact ofYMLI on biomarkers of cellular aging and in promotingcellular longevity through changes in both cardinal andmetabotrophic biomarkers The findings suggest that theimpact is mediated through improvement in genomic sta-bility telomere metabolism and balance of cellular oxidativestress well-regulated stress and inflammatory responses andincrease in neuroplasticity and nutrition sensing

Genomic stability is central to cellular longevity anddisease-free youthful healthy life and the findings from ourstudy suggest the reduction of genomic instability (decreasedlevels of 8-OH2dG) by YMLI Unhealthy social habits (smok-ing excess alcohol intake etc) sedentary lifestyle exposureto environmental pollutants and intake of processed andnutritionally depleted food have taken a toll on humanhealth with the onset of lifestyle diseases at a much youngerage [3ndash5] These environmental and lifestyle factors areresponsible for genomic instability [10] DNAdamage to boththe mitochondrial and nuclear genome from endogenous aswell as exogenous insults results in accumulation of geneticaberrations and genome hypermutability [8ndash10]

This is mainly due to aberrant DNA damage response(DDR) pathway which is essential for DNA repair and formonitoring genomic integrity Deficient DNA repair triggerssystemic effects to promote pathological aging [10] Thereduction of DNA damage by YMLI suggests the potentialof yoga in activating the DDR pathway to repair genomicdamage and improve genomic stability and changes inmetabotrophic factors seen in the study may be associatedwith these benefits

Maintaining telomere length through regulation oftelomere metabolism contributes to genomic stability andthe reduction in telomere attrition (increase in telomere

Oxidative Medicine and Cellular Longevity 5

Table 3 Change in outcomes in apparently healthy sedentary subjects participating in a Yoga- and Meditation-based lifestyle intervention(119899 = 94)

Characteristics Baseline 12 wksChange from baseline to

12wks(diff 95 CI)

Effect sizelowast p value

Primary endpoints cardinal biomarkersof cellular agingOxidative stress

ROS (RLUmin104 neutrophils) 1215069 plusmn 88 102081 plusmn 79 1943 (164 2245) 07 lt00001TAC (mmol Trolox equivL) 594 plusmn 152 74 plusmn 21 minus116 (minus19 minus041) 04 lt0001

DNA damage8OH2dG (pgmL) 102623 plusmn 630 79098 plusmn 400 2353 (7273 3978) 022 lt001

Telomere attritionTelomerase activity (IUcell) 189 plusmn 142 294 plusmn 22 minus105 (minus168 minus041) 03 lt0001Telomere length (IUcell) 236 plusmn 16 244 plusmn 14 minus008 (minus061 045) 002 0069

Secondary endpoints biomarkersassociated with cellular aging

Cortisol (ngmL) 11883plusmn5050 9632 plusmn 386 2251 (76 3742) 03 lt001Interleukin (IL6) (pgmL) 316 plusmn 242 194 plusmn 23 122 (047 197) 03 lt0001120573-Endorphins (ngmL) 62 plusmn 35 82 plusmn 42 minus2 (minus322 minus077) 03 lt0001BDNF (ngmL) 197 plusmn 675 371 plusmn 56 minus174 (minus1948 minus1532) 07 lt00001Sirtuin (ngmL) 2669 plusmn 1042 4064 plusmn 116 minus1395 (minus2341 minus449) 05 lt001

BMI (kgm2) 2630 plusmn 340 2364 plusmn 355 266 (056 312) 04 lt001lowastEffect size was calculated by dividing change by standard deviation at baseline of the specific outcome and interpreted using Cohenrsquos d (small effect 02 to03 medium effect 05 and large effect 08)

length and telomerase activity levels) shown by our studyafter YMLI suggests the potential for yoga in telomeremetabolism and cellular longevity Telomeres which serve asa biological clock are highly conserved hexameric repeatsand maintaining their length is vital for cellular longevityTelomerase is an important regulator of telomere length andaccurate regulation of its activity and a correct telomere-telomerase interaction is important to precisely safeguardtelomere length and prevent telomere attrition [44] ODDis prominent among the factors that can adversely affecttelomere length [45] Rapid telomere attrition due to ODDis associated with senescence and related disease conditions[46 47] Improved telomere metabolism after YMLI seen inthe study may contribute to genomic stability More researchis needed to explore the mechanisms of how yoga andmeditation can positively modify telomere metabolism

Our study suggests an improvement in maintenance ofbalance in cellular oxidative stress (decrease in ROS andincrease in TAC) caused by YMLI Supraphysiological ROSlevels are due to endogenous and exogenous factors likesmoking excess alcohol consumption exposure to elec-tromagnetic radiation infection xenobiotic exposure andpsychological stress [48] Even the levels of ROS belowphysiological limits are deleterious to normal cellular func-tion and maintaining OS at physiological levels is importantfor cellular longevity Increased OS causes damage to allmolecules including damage to DNA and telomeres Italso affects signal transduction and gene transcription bycausing genome-wide hypomethylation [49] and thus causes

changes in the epigenome Regulation of cellular oxidativestress within physiological limits after YMLI suggests thepotential of this intervention in protecting cells from OS-induced DNA damage and telomere attrition and in revers-ing epigenetic changes which are accumulated due to anunhealthy lifestyle and adverse environmental conditionsOther studies [50] support these findings and have shownreducedOSupregulation of telomerase activity anddecreasedODD after YMLI To combat OS people use antioxidantswithout monitoring ROS levels resulting in reductive stress[51] unlike in YMLI which regulates ROS levels so that noredox-sensitive physiological functions are impaired

Modern lifestyle and associated psychological stress havecomplex interactions with habits environmental conditionsandmedical interventions to cause accelerated cellular agingwhich adversely affect our mental physical and reproductivefitness [3ndash5] Improved cellular longevity after YMLI sug-gests the potential role of yoga in promoting this fitnessWhile psychological stress has a major effect on the mindcontributing to an increased prevalence of neuropsychiatricdisorders including depression abnormal fat accumulationis a major somatic manifestation contributing to increasedprevalence of metabolic syndrome and all the diseases thatcome under this umbrella including obesity DM and CVD[52] Other peripheral manifestations of unhealthy modernlifestyle include aging of gonads leading to infertility [53]and recurrent pregnancy loss Previous studies have demon-strated the clinical benefits of yoga and meditation in allthese medical conditions [35] Dada et al have shown that

6 Oxidative Medicine and Cellular Longevity

YMLI can reduce testicular aging and result in significantupregulation in telomerase activity and decline in seminalOS and ODD [8] The ongoing studies in our laboratory onthe impact of yoga and meditation have provided significantevidence for the reversal of cellular aging in subjects proneto accelerated aging due to depression Microarray (Agilent8 times 60k Microarray kit) and analysis of gene expression pre-and post-YMLI showed decreased IL6 IL10 and MAP10 andincreased IL2 and IL4 [8 54 55] Improved cellular longevityseen in our study after YMLI suggests that changes in bothcardinal andmetabotrophic biomarkers of cellular agingmaybe amechanism for preventing chronic lifestyle diseases Ourstudy suggests that the changes in metabotrophic factorswhich include increase in levels of 120573-endorphin BDNF andsirtuin-1 and decrease in levels of cortisol and IL-6 andthe cellular processes involving them may have importantroles in the reversal of cellular aging and improving cellularlongevity after YMLI

Improvements in stress and inflammatory response in ourstudy after YMLI may be mediated by changes in cortisol120573-endorphin IL-6 and other factors with regulation bychanges in the brain through the hypothalamic-pituitary-adrenal (HPA) axis The response may involve regulation ofadaptive pathways including integrated stress response (ISR)[18] that activates eukaryotic translation initiation factor 2alpha (eIF2120572) that promote cellular recovery driving signal-ing toward cell survival and longevityThe response may leadto decreased OS and a reversal of the senescent secretoryphenotype of cells including cells in the brain adipose tissueendothelium and gonads Changes in secretory phenotypeinclude decreased IL-6 [56] increased BDNF and sirtuin-1[57] These regulated factors may lead to balance in OS andcellular longevity and contribute to tissue revival throughoutthe body from neuroplasticity in CNS to gonads vessels andmuscles in the periphery Secretory phenotype from somaticcells provides regulatory feedback to brain [58] whichcompletes the vicious cycle of regulation between mind andbody Neurodegeneration is associated with the pathogenesisof several neuropsychiatric conditions and neuroplasticityhas a central role in their management and for vitalityIncreased BDNF sirtuin-1 and 120573-endorphin and decreasedcortisol each decrease cellular aging in brain decrease neu-rodegeneration and increase neuroplasticity [23] Increasedcellular longevity and increased neuroplasticity may be amechanism for alteration of gray matter volume in differentregions of the cerebral cortex [59] increased mindfulness[60] and several other complex processes [55 61] involvedin reduction of stress and depression after yoga and medi-tation Regulated mind-body communications may lead tominimization of subclinical inflammation and activation ofnutrition and energy-sensing pathways promoting longevitywhere a decrease in IL-6 and an increase in sirtuin-1 play aprominent role respectively Previous studies have demon-strated an increase in sirtuin-1 levels after interventions withcaloric restriction [62] Our study is the first to document anincrease in sirtuin-1 levels independent of caloric restrictionafter practicing yoga These improved processes may resultin delaying onset and slowing down progression of diseasesassociated with accelerated cellular aging

The impact of the intervention in both genders wasassessed separately sincemen andwomen respond differentlyto day-to-day stress [63] Interestingly the gender subgroupanalysis showed that reductions in cortisol and IL6 levelswere more pronounced in male than in female subjectsNo significant gender differences were seen in the otherbiomarkers Phase of the menstrual cycle should be takeninto consideration since some biomarker levels are knownto vary with different phases of the menstrual cycle [64 65]Our study showed a significant decrease in BMI in apparentlyhealthy subjects which came into the normal range (2364 plusmn355) from a baseline overweight range (2630 plusmn 340) Whilethe latest research [66] suggests people with a mean BMI of27 who are overweight by the current classification of obesityare likely to survive longest in a Western population similardata is not available for the Indian populationTherefore ourfindings need to be interpreted cautiously

Stratification of cases was not done in this study to do asubgroup analysis due to the small sample size

Lifestyle is an integrated entity and an intervention likeYMLI that has an overall positive influence on our healthappearsmost useful versus changing only one aspect at a timeas is seen by the action of certain drugs Yoga is holistic anda mind-body medicine and is more beneficial and advan-tageous than individual interventions like physical exercisecaloric restriction and antioxidantsThe practice of yoga andphysical exercise are different entities the former results inenergy conservation with economy of energy expenditure formental and physical benefits and the later results in energyexpendituremore for physical exertions andmetabolic needsas is evident from a study that showed exercise causeserratic changes in biomarkers and results in OS [67] whilemeditation brings about uniform biomarker and behavioralchanges and improvement in cognition and decreaseOS [68]Therapeutic antioxidants can only decrease ROS rather thanregulating it and may paradoxically shorten lifespan [69]due to an imbalance in ROS-mediated immune responses[70] YMLI regulates ROS rather than simply lowering themby balanced stress-related processes and appropriate geneexpression [71] The only limitation of our study is that itis a single-arm proof-of-concept study and did not includecontrols It is important to adopt a lifestyle that slows thedecline in health by reversing or delaying accelerated agingdue to unhealthy lifestyles The biomarkers of cellular agingcan form the basis for determining the risk of chronic lifestylediseases and the efficacy and usefulness of interventions todecrease disease risk Hence the findings from this studyare supportive of YMLI as having significant clinical utilityespecially in the prevention of and management of complexmultifactorial diseases and reducing the rate of functionaldecline with aging

5 Conclusion

Though we cannot change our biology or chronological agewe can definitely reverseslow down the pace at which weage by adopting YMLI This is the first study to demonstrateimprovement in both cardinal and metabotrophic biomark-ers of cellular aging and longevity in an apparently healthy

Oxidative Medicine and Cellular Longevity 7

population after a yoga- and meditation-based lifestyle inter-vention Our health and the rate at which we age entirelydepends on our choices Making yoga and meditation anintegral part of our lifestylemay hold the key to delay aging oraging gracefully prevent the onset of multifactorial complexlifestyle diseases promote mental physical and reproductivehealth and prolong youthful healthy life

Conflicts of Interest

Theauthors declare there are no conflicts of interest regardingthe publication of this article

Acknowledgments

The authors are thankful to Amit Tomar and SudhirChoudary for yoga instructions and to all the subjectsenrolled in the study

References

[1] M Tolahunase R Sagar and R Dada ldquoImpact of yoga andmeditation on cellular aging in apparently healthy individu-als a prospective open-label single-arm exploratory studyrdquoOxidative Medicine and Cellular Longevity vol 2017 Article ID7928981 9 pages 2017

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 5: Erratum - Hindawi

Oxidative Medicine and Cellular Longevity 5

Table 3 Change in outcomes in apparently healthy sedentary subjects participating in a Yoga- and Meditation-based lifestyle intervention(119899 = 94)

Characteristics Baseline 12 wksChange from baseline to

12wks(diff 95 CI)

Effect sizelowast p value

Primary endpoints cardinal biomarkersof cellular agingOxidative stress

ROS (RLUmin104 neutrophils) 1215069 plusmn 88 102081 plusmn 79 1943 (164 2245) 07 lt00001TAC (mmol Trolox equivL) 594 plusmn 152 74 plusmn 21 minus116 (minus19 minus041) 04 lt0001

DNA damage8OH2dG (pgmL) 102623 plusmn 630 79098 plusmn 400 2353 (7273 3978) 022 lt001

Telomere attritionTelomerase activity (IUcell) 189 plusmn 142 294 plusmn 22 minus105 (minus168 minus041) 03 lt0001Telomere length (IUcell) 236 plusmn 16 244 plusmn 14 minus008 (minus061 045) 002 0069

Secondary endpoints biomarkersassociated with cellular aging

Cortisol (ngmL) 11883plusmn5050 9632 plusmn 386 2251 (76 3742) 03 lt001Interleukin (IL6) (pgmL) 316 plusmn 242 194 plusmn 23 122 (047 197) 03 lt0001120573-Endorphins (ngmL) 62 plusmn 35 82 plusmn 42 minus2 (minus322 minus077) 03 lt0001BDNF (ngmL) 197 plusmn 675 371 plusmn 56 minus174 (minus1948 minus1532) 07 lt00001Sirtuin (ngmL) 2669 plusmn 1042 4064 plusmn 116 minus1395 (minus2341 minus449) 05 lt001

BMI (kgm2) 2630 plusmn 340 2364 plusmn 355 266 (056 312) 04 lt001lowastEffect size was calculated by dividing change by standard deviation at baseline of the specific outcome and interpreted using Cohenrsquos d (small effect 02 to03 medium effect 05 and large effect 08)

length and telomerase activity levels) shown by our studyafter YMLI suggests the potential for yoga in telomeremetabolism and cellular longevity Telomeres which serve asa biological clock are highly conserved hexameric repeatsand maintaining their length is vital for cellular longevityTelomerase is an important regulator of telomere length andaccurate regulation of its activity and a correct telomere-telomerase interaction is important to precisely safeguardtelomere length and prevent telomere attrition [44] ODDis prominent among the factors that can adversely affecttelomere length [45] Rapid telomere attrition due to ODDis associated with senescence and related disease conditions[46 47] Improved telomere metabolism after YMLI seen inthe study may contribute to genomic stability More researchis needed to explore the mechanisms of how yoga andmeditation can positively modify telomere metabolism

Our study suggests an improvement in maintenance ofbalance in cellular oxidative stress (decrease in ROS andincrease in TAC) caused by YMLI Supraphysiological ROSlevels are due to endogenous and exogenous factors likesmoking excess alcohol consumption exposure to elec-tromagnetic radiation infection xenobiotic exposure andpsychological stress [48] Even the levels of ROS belowphysiological limits are deleterious to normal cellular func-tion and maintaining OS at physiological levels is importantfor cellular longevity Increased OS causes damage to allmolecules including damage to DNA and telomeres Italso affects signal transduction and gene transcription bycausing genome-wide hypomethylation [49] and thus causes

changes in the epigenome Regulation of cellular oxidativestress within physiological limits after YMLI suggests thepotential of this intervention in protecting cells from OS-induced DNA damage and telomere attrition and in revers-ing epigenetic changes which are accumulated due to anunhealthy lifestyle and adverse environmental conditionsOther studies [50] support these findings and have shownreducedOSupregulation of telomerase activity anddecreasedODD after YMLI To combat OS people use antioxidantswithout monitoring ROS levels resulting in reductive stress[51] unlike in YMLI which regulates ROS levels so that noredox-sensitive physiological functions are impaired

Modern lifestyle and associated psychological stress havecomplex interactions with habits environmental conditionsandmedical interventions to cause accelerated cellular agingwhich adversely affect our mental physical and reproductivefitness [3ndash5] Improved cellular longevity after YMLI sug-gests the potential role of yoga in promoting this fitnessWhile psychological stress has a major effect on the mindcontributing to an increased prevalence of neuropsychiatricdisorders including depression abnormal fat accumulationis a major somatic manifestation contributing to increasedprevalence of metabolic syndrome and all the diseases thatcome under this umbrella including obesity DM and CVD[52] Other peripheral manifestations of unhealthy modernlifestyle include aging of gonads leading to infertility [53]and recurrent pregnancy loss Previous studies have demon-strated the clinical benefits of yoga and meditation in allthese medical conditions [35] Dada et al have shown that

6 Oxidative Medicine and Cellular Longevity

YMLI can reduce testicular aging and result in significantupregulation in telomerase activity and decline in seminalOS and ODD [8] The ongoing studies in our laboratory onthe impact of yoga and meditation have provided significantevidence for the reversal of cellular aging in subjects proneto accelerated aging due to depression Microarray (Agilent8 times 60k Microarray kit) and analysis of gene expression pre-and post-YMLI showed decreased IL6 IL10 and MAP10 andincreased IL2 and IL4 [8 54 55] Improved cellular longevityseen in our study after YMLI suggests that changes in bothcardinal andmetabotrophic biomarkers of cellular agingmaybe amechanism for preventing chronic lifestyle diseases Ourstudy suggests that the changes in metabotrophic factorswhich include increase in levels of 120573-endorphin BDNF andsirtuin-1 and decrease in levels of cortisol and IL-6 andthe cellular processes involving them may have importantroles in the reversal of cellular aging and improving cellularlongevity after YMLI

Improvements in stress and inflammatory response in ourstudy after YMLI may be mediated by changes in cortisol120573-endorphin IL-6 and other factors with regulation bychanges in the brain through the hypothalamic-pituitary-adrenal (HPA) axis The response may involve regulation ofadaptive pathways including integrated stress response (ISR)[18] that activates eukaryotic translation initiation factor 2alpha (eIF2120572) that promote cellular recovery driving signal-ing toward cell survival and longevityThe response may leadto decreased OS and a reversal of the senescent secretoryphenotype of cells including cells in the brain adipose tissueendothelium and gonads Changes in secretory phenotypeinclude decreased IL-6 [56] increased BDNF and sirtuin-1[57] These regulated factors may lead to balance in OS andcellular longevity and contribute to tissue revival throughoutthe body from neuroplasticity in CNS to gonads vessels andmuscles in the periphery Secretory phenotype from somaticcells provides regulatory feedback to brain [58] whichcompletes the vicious cycle of regulation between mind andbody Neurodegeneration is associated with the pathogenesisof several neuropsychiatric conditions and neuroplasticityhas a central role in their management and for vitalityIncreased BDNF sirtuin-1 and 120573-endorphin and decreasedcortisol each decrease cellular aging in brain decrease neu-rodegeneration and increase neuroplasticity [23] Increasedcellular longevity and increased neuroplasticity may be amechanism for alteration of gray matter volume in differentregions of the cerebral cortex [59] increased mindfulness[60] and several other complex processes [55 61] involvedin reduction of stress and depression after yoga and medi-tation Regulated mind-body communications may lead tominimization of subclinical inflammation and activation ofnutrition and energy-sensing pathways promoting longevitywhere a decrease in IL-6 and an increase in sirtuin-1 play aprominent role respectively Previous studies have demon-strated an increase in sirtuin-1 levels after interventions withcaloric restriction [62] Our study is the first to document anincrease in sirtuin-1 levels independent of caloric restrictionafter practicing yoga These improved processes may resultin delaying onset and slowing down progression of diseasesassociated with accelerated cellular aging

The impact of the intervention in both genders wasassessed separately sincemen andwomen respond differentlyto day-to-day stress [63] Interestingly the gender subgroupanalysis showed that reductions in cortisol and IL6 levelswere more pronounced in male than in female subjectsNo significant gender differences were seen in the otherbiomarkers Phase of the menstrual cycle should be takeninto consideration since some biomarker levels are knownto vary with different phases of the menstrual cycle [64 65]Our study showed a significant decrease in BMI in apparentlyhealthy subjects which came into the normal range (2364 plusmn355) from a baseline overweight range (2630 plusmn 340) Whilethe latest research [66] suggests people with a mean BMI of27 who are overweight by the current classification of obesityare likely to survive longest in a Western population similardata is not available for the Indian populationTherefore ourfindings need to be interpreted cautiously

Stratification of cases was not done in this study to do asubgroup analysis due to the small sample size

Lifestyle is an integrated entity and an intervention likeYMLI that has an overall positive influence on our healthappearsmost useful versus changing only one aspect at a timeas is seen by the action of certain drugs Yoga is holistic anda mind-body medicine and is more beneficial and advan-tageous than individual interventions like physical exercisecaloric restriction and antioxidantsThe practice of yoga andphysical exercise are different entities the former results inenergy conservation with economy of energy expenditure formental and physical benefits and the later results in energyexpendituremore for physical exertions andmetabolic needsas is evident from a study that showed exercise causeserratic changes in biomarkers and results in OS [67] whilemeditation brings about uniform biomarker and behavioralchanges and improvement in cognition and decreaseOS [68]Therapeutic antioxidants can only decrease ROS rather thanregulating it and may paradoxically shorten lifespan [69]due to an imbalance in ROS-mediated immune responses[70] YMLI regulates ROS rather than simply lowering themby balanced stress-related processes and appropriate geneexpression [71] The only limitation of our study is that itis a single-arm proof-of-concept study and did not includecontrols It is important to adopt a lifestyle that slows thedecline in health by reversing or delaying accelerated agingdue to unhealthy lifestyles The biomarkers of cellular agingcan form the basis for determining the risk of chronic lifestylediseases and the efficacy and usefulness of interventions todecrease disease risk Hence the findings from this studyare supportive of YMLI as having significant clinical utilityespecially in the prevention of and management of complexmultifactorial diseases and reducing the rate of functionaldecline with aging

5 Conclusion

Though we cannot change our biology or chronological agewe can definitely reverseslow down the pace at which weage by adopting YMLI This is the first study to demonstrateimprovement in both cardinal and metabotrophic biomark-ers of cellular aging and longevity in an apparently healthy

Oxidative Medicine and Cellular Longevity 7

population after a yoga- and meditation-based lifestyle inter-vention Our health and the rate at which we age entirelydepends on our choices Making yoga and meditation anintegral part of our lifestylemay hold the key to delay aging oraging gracefully prevent the onset of multifactorial complexlifestyle diseases promote mental physical and reproductivehealth and prolong youthful healthy life

Conflicts of Interest

Theauthors declare there are no conflicts of interest regardingthe publication of this article

Acknowledgments

The authors are thankful to Amit Tomar and SudhirChoudary for yoga instructions and to all the subjectsenrolled in the study

References

[1] M Tolahunase R Sagar and R Dada ldquoImpact of yoga andmeditation on cellular aging in apparently healthy individu-als a prospective open-label single-arm exploratory studyrdquoOxidative Medicine and Cellular Longevity vol 2017 Article ID7928981 9 pages 2017

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 6: Erratum - Hindawi

6 Oxidative Medicine and Cellular Longevity

YMLI can reduce testicular aging and result in significantupregulation in telomerase activity and decline in seminalOS and ODD [8] The ongoing studies in our laboratory onthe impact of yoga and meditation have provided significantevidence for the reversal of cellular aging in subjects proneto accelerated aging due to depression Microarray (Agilent8 times 60k Microarray kit) and analysis of gene expression pre-and post-YMLI showed decreased IL6 IL10 and MAP10 andincreased IL2 and IL4 [8 54 55] Improved cellular longevityseen in our study after YMLI suggests that changes in bothcardinal andmetabotrophic biomarkers of cellular agingmaybe amechanism for preventing chronic lifestyle diseases Ourstudy suggests that the changes in metabotrophic factorswhich include increase in levels of 120573-endorphin BDNF andsirtuin-1 and decrease in levels of cortisol and IL-6 andthe cellular processes involving them may have importantroles in the reversal of cellular aging and improving cellularlongevity after YMLI

Improvements in stress and inflammatory response in ourstudy after YMLI may be mediated by changes in cortisol120573-endorphin IL-6 and other factors with regulation bychanges in the brain through the hypothalamic-pituitary-adrenal (HPA) axis The response may involve regulation ofadaptive pathways including integrated stress response (ISR)[18] that activates eukaryotic translation initiation factor 2alpha (eIF2120572) that promote cellular recovery driving signal-ing toward cell survival and longevityThe response may leadto decreased OS and a reversal of the senescent secretoryphenotype of cells including cells in the brain adipose tissueendothelium and gonads Changes in secretory phenotypeinclude decreased IL-6 [56] increased BDNF and sirtuin-1[57] These regulated factors may lead to balance in OS andcellular longevity and contribute to tissue revival throughoutthe body from neuroplasticity in CNS to gonads vessels andmuscles in the periphery Secretory phenotype from somaticcells provides regulatory feedback to brain [58] whichcompletes the vicious cycle of regulation between mind andbody Neurodegeneration is associated with the pathogenesisof several neuropsychiatric conditions and neuroplasticityhas a central role in their management and for vitalityIncreased BDNF sirtuin-1 and 120573-endorphin and decreasedcortisol each decrease cellular aging in brain decrease neu-rodegeneration and increase neuroplasticity [23] Increasedcellular longevity and increased neuroplasticity may be amechanism for alteration of gray matter volume in differentregions of the cerebral cortex [59] increased mindfulness[60] and several other complex processes [55 61] involvedin reduction of stress and depression after yoga and medi-tation Regulated mind-body communications may lead tominimization of subclinical inflammation and activation ofnutrition and energy-sensing pathways promoting longevitywhere a decrease in IL-6 and an increase in sirtuin-1 play aprominent role respectively Previous studies have demon-strated an increase in sirtuin-1 levels after interventions withcaloric restriction [62] Our study is the first to document anincrease in sirtuin-1 levels independent of caloric restrictionafter practicing yoga These improved processes may resultin delaying onset and slowing down progression of diseasesassociated with accelerated cellular aging

The impact of the intervention in both genders wasassessed separately sincemen andwomen respond differentlyto day-to-day stress [63] Interestingly the gender subgroupanalysis showed that reductions in cortisol and IL6 levelswere more pronounced in male than in female subjectsNo significant gender differences were seen in the otherbiomarkers Phase of the menstrual cycle should be takeninto consideration since some biomarker levels are knownto vary with different phases of the menstrual cycle [64 65]Our study showed a significant decrease in BMI in apparentlyhealthy subjects which came into the normal range (2364 plusmn355) from a baseline overweight range (2630 plusmn 340) Whilethe latest research [66] suggests people with a mean BMI of27 who are overweight by the current classification of obesityare likely to survive longest in a Western population similardata is not available for the Indian populationTherefore ourfindings need to be interpreted cautiously

Stratification of cases was not done in this study to do asubgroup analysis due to the small sample size

Lifestyle is an integrated entity and an intervention likeYMLI that has an overall positive influence on our healthappearsmost useful versus changing only one aspect at a timeas is seen by the action of certain drugs Yoga is holistic anda mind-body medicine and is more beneficial and advan-tageous than individual interventions like physical exercisecaloric restriction and antioxidantsThe practice of yoga andphysical exercise are different entities the former results inenergy conservation with economy of energy expenditure formental and physical benefits and the later results in energyexpendituremore for physical exertions andmetabolic needsas is evident from a study that showed exercise causeserratic changes in biomarkers and results in OS [67] whilemeditation brings about uniform biomarker and behavioralchanges and improvement in cognition and decreaseOS [68]Therapeutic antioxidants can only decrease ROS rather thanregulating it and may paradoxically shorten lifespan [69]due to an imbalance in ROS-mediated immune responses[70] YMLI regulates ROS rather than simply lowering themby balanced stress-related processes and appropriate geneexpression [71] The only limitation of our study is that itis a single-arm proof-of-concept study and did not includecontrols It is important to adopt a lifestyle that slows thedecline in health by reversing or delaying accelerated agingdue to unhealthy lifestyles The biomarkers of cellular agingcan form the basis for determining the risk of chronic lifestylediseases and the efficacy and usefulness of interventions todecrease disease risk Hence the findings from this studyare supportive of YMLI as having significant clinical utilityespecially in the prevention of and management of complexmultifactorial diseases and reducing the rate of functionaldecline with aging

5 Conclusion

Though we cannot change our biology or chronological agewe can definitely reverseslow down the pace at which weage by adopting YMLI This is the first study to demonstrateimprovement in both cardinal and metabotrophic biomark-ers of cellular aging and longevity in an apparently healthy

Oxidative Medicine and Cellular Longevity 7

population after a yoga- and meditation-based lifestyle inter-vention Our health and the rate at which we age entirelydepends on our choices Making yoga and meditation anintegral part of our lifestylemay hold the key to delay aging oraging gracefully prevent the onset of multifactorial complexlifestyle diseases promote mental physical and reproductivehealth and prolong youthful healthy life

Conflicts of Interest

Theauthors declare there are no conflicts of interest regardingthe publication of this article

Acknowledgments

The authors are thankful to Amit Tomar and SudhirChoudary for yoga instructions and to all the subjectsenrolled in the study

References

[1] M Tolahunase R Sagar and R Dada ldquoImpact of yoga andmeditation on cellular aging in apparently healthy individu-als a prospective open-label single-arm exploratory studyrdquoOxidative Medicine and Cellular Longevity vol 2017 Article ID7928981 9 pages 2017

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 7: Erratum - Hindawi

Oxidative Medicine and Cellular Longevity 7

population after a yoga- and meditation-based lifestyle inter-vention Our health and the rate at which we age entirelydepends on our choices Making yoga and meditation anintegral part of our lifestylemay hold the key to delay aging oraging gracefully prevent the onset of multifactorial complexlifestyle diseases promote mental physical and reproductivehealth and prolong youthful healthy life

Conflicts of Interest

Theauthors declare there are no conflicts of interest regardingthe publication of this article

Acknowledgments

The authors are thankful to Amit Tomar and SudhirChoudary for yoga instructions and to all the subjectsenrolled in the study

References

[1] M Tolahunase R Sagar and R Dada ldquoImpact of yoga andmeditation on cellular aging in apparently healthy individu-als a prospective open-label single-arm exploratory studyrdquoOxidative Medicine and Cellular Longevity vol 2017 Article ID7928981 9 pages 2017

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 8: Erratum - Hindawi

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom