Professor Tahir Masud

President, British Geriatrics Society President Elect, British Geriatrics Society

Nottingham University Hospitals NHS Trust University of Nottingham

University of Southern Denmark

Sarcopenia

Twitter @TashMasud

Disclosures

I have no conflict of interest or disclosure in relation to this

presentation

Sarcopenia- What is it?Greek:

”Poverty of flesh”

Rosenberg 1989:

”There is probably no decline in structure and function more dramatic than the decline in lean body mass or muscle mass over decades of life”

European Working Group on Sarcopenia in Older People (EWGSOP) 2010

”Sarcopenia is a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength with a risk of adverse outcomes such as:- physical disability- poor quality of life- death”

Sarcopenia

• Loss of muscle mass and function (strength or performace)

• Prevalence increases with age

• Associated with disability, morbidity, frailty, falls and mortality

• ICD condition

• Prevalence varies according to definition & cut-offs

- 60-70 years: 5-13%

- 80+ years: 11-50%

A Lifecourse Approach to Sarcopenia

Sayer AA, et al J Nutr Health Aging. 2008

What Causes Sarcopenia?Risk factors

• Older age• Females• Muscle disuse (low physical activity & immobility)

Cellular Level

• Reduced muscle fibre size & number [both type 1 (slow) and type 2 (fast)]

• Oxidative damage

• Nutritional (eg -anabolic resistance to protein-malnutrition)

• Hormonal (eg IGF-1, renin-angiotensin system, sex hormones)

• Loss of muscle fibre innervation

Neurologoical origin of sarcopenia ?

Casati et al 2019

Identified hub genes and proteins of muscle development

Shafiee et al 2018

2019

27 articles

18 genes studied in at least 3 article

How to Diagnose Sarcopenia?EWGSOP algorithm for diagnosing sarcopenia

Cruz-Jentoft et al Age Ageing 2010

Different Sarcopenia Diagnostic Criteria

IANA = Int. Academy on Nutrition & Ageing; EWGSOP = Europ.WG on Sarcopenia in Older People; AWGS = Asian WG on SarcopeniaFNIH = Foundation for the National Institutes of Health sarcopenia Project

Keevil & Romero-Ortuno(2015)

Sarcopenia: Revised European Consensus on Definition and Diagnosis

Age Ageing 2019

Cruz-Jentoft et al

+Concept of

”Acute Sarcopenia”

SARC F

Interventions for Sarcopenia

• Resistance Exercises• Nutrition

- Protein- Essential Amino Acids- Vitamin D

• Therapeutic Advances?- Myostatin inhibitors- SARMS- ACEIs

combination

Types of Exercises Recommended for Older Adults

1. Aerobic• brisk walk, jog, swim, cycle, dance, aerobic

2. Progressive Resistance• weights, resistance bands• stairs• pull-ups, push-ups• heavy loads, heavy gardening

3. Flexibility• yoga, Tai Chi

4. Balance Training• static- stand on one leg• dynamic- (semi-) tandem, walk backwards• Tai Chi

Montero-Fernandez & Serra-Rexach 2013- Eur J Phys Rehabil Med

18

Physical Activity Guidelines (UK Chief Medical Officer:Updated Sept 2019)

(similar to WHO Global Strategy on Diet, Physical Activity and Health)

Image (c) Public Health England, Department of Health, UK

19

Image (c) Public Health England, Department of Health, UK

• Muscles contain proteins as one of its important consistuents

• Proteins are made of individual units of amino acids (AAs) that are linked together

• The order of the AAs allows different proteins to have different functions

Nutrition

Amino Acids

• Body uses 20 different amino acids to make proteins

• 9 of the 20 amino acids must be essential amino acids (EAA) – Body cannot make them on its own– Therefore must be consumed in the diet

• Other 11 amino acids are non-essential (NEAA)– Can be made from other amino acids in the diet

Leucine Tryptophan MethionineIsoleucine Threonine LysineValine Histidine Phenylalanine

Berg JM, et al. Biochemistry. 5th ed. New York, NY: WH Freeman & Co.; 2002.21

Basic Structure of an Amino Acid• Central carbon atom (alpha carbon [Cα]) linked to

– Amino group (positive)– Carboxylic acid group (negative)– Hydrogen– Distinctive side chain (R)

• Makes each AA different

Berg JM, et al. Biochemistry. 5th ed. New York, NY: WH Freeman & Co.; 2002.22

–

R

Core Group

Unique side-chain

(simplest AA is Glycine where R = H)

Branched Chain Amino Acids (BCAAs)

• Unlike other amino acids, most BCAA metabolism occurs in skeletal muscle (liver lacks the enzymes that break down BCAAs)

• Leucine is also unique among AAs in its ability to stimulate synthesis of new muscle proteins

• Mechanism?- Leucine may activate mTOR signaling pathway that stimulates muscle protein synthesis?

H3C

H3CCH-

H3C

H3CCH-CH2-

CH2CH2

CH-

CH3

C COO-

NH3+

H

C COO-

NH3+

H

C COO-

NH3+

H

Tom A, et al. J Nutr. 2006;136(suppl 1): 324S-330S.

Leucine Isoleucine Valine

23(mTOR= mammalian target of rapamycin)

β-hydroxy-β-methylbutyrate (HMB)

– A breakdown product of leucine is HMB

– Some evidence suggests that HMB inhibits muscle protein breakdown and increases muscle synthesis, especially in combination with exercise

– Some studies suggest that HMB may provide greater benefit to untrained people who start weight training compared with previously trained athletes

Nemet D, et al. Isr Med Assoc J. 2005;7(5):328-332.Nissen S, et al. J Appl Physiol. 1996;81(5):2095-2104. (Smith et al. Cancer research 2004)

Optimal Protein Intakes

(Franzke et al, Nutrients 2018)

• Old age → Anabolic Resistance (Impaired MPS )

• Physical Inactivity → Anabolic Resistance

• MPS rates higher after exercise (↑ Anabolic Sensitivity, timing may be important)

• WHO recommendations 2007 for all age groups: 0.8 g/kg/day• Some countries (Australia, Nordic) guidelines for older people : 1.1- 1.3 g/kg/day• ESPEN : Healthy adults ≥65 yrs: 1.0-1.2 g/kg/day

Chronically ill or malnourished: 1.2- 1.5 g/kg/day

• Max stimulation for MPS: 0.4 g/kg per meal • Even protein intake is better than Skewed protein intake: 25-30 g per each meal

Protein / AA intake

Muscle contraction(Exercise – Resistance + Endurance)

Muscle Protein synthesis (MPS)

• Whey protein stimulated postprandial protein accreditation more effectively than casein (faster digestion and absorption and more leucine content)

• Mince beef may be better than steak in leading to a better protein balance in older people (better digested and absorbed)

• Liquid protein foods eg milk, yoghurts are considered effective sources of high quality protein for older adults

• Plant based proteins are considered less anabolic(lower content of essential AAs and leucine)

• Adequate protein intake can still be acheived by plant based diets

• Multiple plant and animal protein whole food sources provide a broad variety of macro- and micronutrients, fibre, plant bioactive compounds etc , all of which might be particularly important in the over 85 year population

Different Food Sources of Protein

Leucine and ACEis in Sarcopenia (LACE) Trial

• Multicentre RCT in > 15 UK centres (including Nottingham, Derby, Leicester)

• CI: Miles Whitham (Dundee)

• 2 x 2 factorial design• Perindpopril 4mg + placaebo• Leucine tds + placaebo• Perindopril + leucine• Double placaebo

• Primary outcome - SPPB

• Secondary oiutcomes:• Muscle mass• Falls• QoL• Health economics

Sarcopenic Obesity

From: Lombardo et al 2019 Eur Rev Med Pharmacol Sci

From Choi 2016, Korean J Int Med

From: Zamboni, M Verona, Italy

2019

Mean age = 80, n=58, women = 62%

Mean grip strength: 17.9kg (women), 29.9kg (men)

Mean Muscle mass (BIA): 6.98 (women), and 7.85 (men) kg/m2 (ASMI)

Mean gait speeds 0.61m/s (women), 0.72 m/s (men)

Prevalence of sarcopenia = 9.8%

Introducing the Concepts of Sarcopenia, Frailty and Malnutrition in Busy Osteoporosis Clinic

A Service Improvement Project

Arrain M, et al 2018, presented at the Spring BGS 2018

”Osteosarcopenia”, ”Sarcoporosis”

Muscle mass

Bioimpedance

Hand Grip Strength

Jamar

Gait Speed

4 metres

• 63 patients (55 women), age range 63-93, mean 78 years

• Slow gait speed (≤ 0.8m/s) - 55.7% (34/61)

• Women with reduced grip strength (< 20kg) - 62.5% (35/56) • Men with reduced grip strength (< 30kg) - 71.4% (5/7)

• Women with low muscle mass (< 6.42 kg/m2) - 59.2% (29/49) • Men with low muscle mass (<8.87 kg/m2) - 85.7% (6/7)

• 41% of the patients were classified as sarcopenic(Women 36.7% , men 71.4%)

• Frailty (GFI score ≥4) was diagnosed in 66.7% (42/63)

• 7.9% (5/63) of patients were malnourished (MNA-SF score ≤7)

Falls

Frailty

Sarcopenia

Nutrition↓

FracturesOsteoporosis

Summary: Inter-related Factors in Fracture Pathogenesis

Interventions:

Exercise & Physical Activity

+Nutrition

Summary

• Sarcopenia is now an ICD classified condition

• Associated with disability, morbidity, falls, poor quality of life and mortality

• Is underecognised

• If suspected a probale diagnosis can be made with grip strength or chair stand test

• Confirmation requires muscle mass measurement (DEXA, bioimpedance, CT, MRI)

• There is much ovelap between sarcopenia and frailty

• Resistance exercise has the most evidence for treating and preventing sarcopenia

• There is emergiong evidence for the role of protein in prevention & treatment of sarcopenia

”Lack of activity destroys the good condition of every human being while movement and methodological

physical exercise saves it and preserves it”Plato

Thank you for your attentionTwitter: @TashMasud

“Exercise (“Riazat”) if used correctly, intermediately and in an appropriate time, can prevent some diseases.

Exercise creates heat in body which helps defecating of wastes out of body and enriches digestion to digest food completely so it results in preventing from accumulation of accessory materials or undigested substances in body”.

Avicenna (Ibn Sina) 980-1037AD Arabic Canon pp229-234