report nutri.PDF

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Physiology of AgeingDr Tessa La Varis

Consultant General Physician & Geriatrician

11 March 2011


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Principles of Ageing

Theories of Ageing

Ageing of Specific SystemsExternal appearance

Brain/Neurology

Heart/LungsEndocrine/Metabolic

Musculoskeletal

Genitourinary

Successful Agers

Frailty

Anti-Ageing Phenomenon


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Age and age related diseases are not the same

Those manifestations that are universally present in allelderly and increase in magnitude with advancing age

represent ageing

There are a range of individual responses to ageing

Body systems do not age at the same rate

Even changes that are considered normal do not result ininevitable consequences

First detectable as a loss of reserve capacity


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Normal ageing in the absence of disease isquite benign. Although organs graduallylose function, changes are not always

noticed until times of great exertion andstress.


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Theories of Ageing

The Evolutionary Theory Defines ageing in terms of natural

selection and its relationship withfertility

The Grandmother Effect

Mutation accumulation theory Ageing is an inevitable result of

the declining force of naturalselection

Mutant genes that kill young willbe strongly selected against

Lethal mutation that kills the oldwill experience no selection andover generations will accumulate

Antagonistic Pleiotrophy Genes beneficial at younger age

become deleterious at older ages


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Theories of Ageing

Telomerase Theory of Aging Normal cells lose the ability to divide after ~50x in vitro (cellular senescence).

Related to telomere length. Shorten with each division.

Each time a cell divides, it duplicates itself a little worse eventually leading tocellular dysfunction and death

This is protective against malignancy Does not occur in all organisms or cell lines (cellular immortality)

The Rate of Living Theory/Free Radical Theory Free radicals (by-product of normal metabolism)

Damage cells

Theory: metabolismlongevity

Theory proven in Roundworm &

Fruit-fly but not Mice


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Ageing on the Outside


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Ageing on the Outside

Skin Oil glands and underlying

fat thinner/drier/wrinkly Atrophy of sweat glands

heat tolerance Age Spots Solar Lentigo Deposits of melanin in skin

(sun exposure)

Nails

thicken due to bloodsupply growth 50%

Hair thins and loses pigment


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Ageing Brain

Number of inter-neuronalconnections in some parts

of the brain Personality and Sense of

Self is unchanged

Weight and volume of brainby 2%/decade from earlyadulthood

Neurotransmitters Serotonin Acetylcholine Dopamine

Neuron density 30% by age 80


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Ageing Cognitive Function

Frontal lobe is most negativelyaffected by normal ageing Speed of processing and

learning new information

Working memory (retention ofinformation that must bemanipulated)

Difficulty with word retrieval Difficulty distinguishing relevant

and irrelevant information to a taskresulting in impaired attention.

Changes to executive function

Positive Changes Greater experienced based

knowledge

Increased accuracy

Better judgement Better ability to handle familiar

tasks


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Ageing Cognition

Changes happen to everyone to adegree with wide variation.

In many the changes are undetectableand should not interfere with normalday to day functioning

By the age of 80 only 30-40% ofpeople have a significant declinein mental ability

Memory problems that arenot part of normal ageing:

Forgetting things much moreoften than you used to

Forgetting how to do thingsyouve done many times before

Trouble learning new things

Repeating phrases or stories inthe same conversation

Trouble making choices orhandling money

Not being able to keep track ofwhat happens each day


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Ageing Co-ordination

Delay in speed of nerve

conduction Reaction time

and Sensation

Proprioception

Cerebellar andVestibular cells

Balance


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Ageing Senses - Vision

Pupils less responsive Tolerance to glare

Need for illumination

Light/dark adaptation

Retinal Changes Colour perception

Contrast sensitivity

Hardening of lenses Depth perception

Accommodation


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Ageing Senses Hearing & Taste

Hearing 50% >85yrs experience

significant hearing loss

Eardrums thicken,auditory canal walls thin

High frequency hearing

Taste Number of taste buds

Sense of thirst


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Ageing Sleep

Melatonin secretion islower

Slow wave/delta sleep

Latency to sleep onset

Awakenings

Tendency for sleepingand sleepiness during theday


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Maturity is a Distinct Phenomenon

from Ageing


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Ageing Heart

Increasing arterial rigidity

Heart muscle efficiency diastolic dysfunction

Impaired baroreceptor response postural hypotension

Response to adrenergicstimulation maximum attainable stroke volume / ejection fraction /

cardiac output

oxygen delivery

Complicated by presence of disease


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Ageing Lungs

Structural support for smallairways number of small airways open susceptibility to infection

CNS responsiveness

Muscle mass including muscles ofrespiration

Elasticity Vital capacity loss of 5-20% of

functional ability/decade

Residual volume

PaO2 Age 20 952 Age 75 73mmHg 5


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Ageing Endocrine Hormones

Hypothalamic PituitaryFunction

Circadian rhythm shifts

Reduced GH

Lean body mass andbone density

Adrenocortical Function

Sustained cortisol levels

?Effect

DHEADehydroepiandrosterone

Precursor to Estrogen andAndrogen

Concentration 80%between age 2080

No clear consequence


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Ageing Eating

Factors causing weight loss with age


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Ageing Metabolism

1% metabolic rate/year >25

Proportion of body fat doubles age2575 Can be influenced by exercise

Susceptibility to drug toxicity

Weight

Men until 50s then

Women until 60s then slow

Glucose regulation

insulin sensitivity (50%)

insulin production (Variable)


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Obesity, Muscles and Exercise

As we age, fat increases and muscle and bone decrease,worsened by chronic inflammation and inactivity=sarcopenic obesity

Skeletal muscle mass decreases 3kg/decade from age

45yrs; strength reduces 1-2%/yr from 40yrs

Resistance training increases muscle mass and strength,decreases fatty infiltration of muscle, mobilises visceralfat, decreases insulin resistance, improves gait, balance andfunction

Adding aerobic exercise further reduces diabetes and CVDrisk, but requires muscle to start with!

Visceral adiposity increases with age and is high risk, soconsider measuring waist-hip ratio


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Relative Risk of Death Associated

with Obesity Decreases with Age


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Avoiding Weight Loss

Anker 1997: Wt loss >7.5% = RR 3.73 mortality

Fiedal 2005: BMI 60 year olds increasesmortality

4.8% malnourished and 38.4% at risk of it indomiciliary care in Adelaide 2003

Starvation: low caloric intake causes low LBM andfat mass, this CAN be reversed with feeding

Sarcopenia: low LBM, stable weight (measure mid-arm circumference to detect)

Cachexia: chronic inflammatory disease, cytokine

mediated, CAN NOT be reversed with feeding


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But It Happens Anyway


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Ageing Musculoskeletal

Bones Maximum mass Age 25-35

Vertebral thinning Height

Vertebral calcification Rigidity

Joints Weight bearing joint space

Height until age 40 then up to 5cm by age 80

Proprioception


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Ageing Vitamin D & Calcium

Vitamin D Important for bone and

muscle strength

With age, generation fromsun exposure

Conversion 25 - 1,25hydroxy vitamin D

Resistance to Vitamin D action

Calcium absorption isdecreased

Osteoporosis Estrogens (and testosterone

to lesser extent) combinewith the above to lead toreduced bone mineral density


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Ageing Menopause

Abrupt change

Estrogens & Androgens

=Menopause

Menstrual irregularity Uterine wall changes

Vasomotor Hot Flushes Hypothalamus thermoregulation

dysfunction

Vaginal and Urethral changes

Sleep disturbances


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Ageing Male Hormones

Testosterone (1%/year) from20s

Sperm production stable 70then 50% by age 90

Variable consequences

Andropause? Sexual function

Bone density muscle mass/strength

Cognitive function

Trials of testosteronereplacement BMD if levels very low

Muscle mass but not strength

No change in QOL and sexual function

Potential increase in disease


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Ageing Genitourinary

Bladder sphincter muscles losestrength

Vagina Lubricates more slowlyand with less amount

Shortens and narrows

Prostate enlarges

Kidneys lose 20% mass age 40-80

GFR 1ml/min/yr >40 (normal

80-120) (Serum creatinine poor measure)

ability to dilute andconcentrate urine


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Successful Ageing is Happening


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Successful Agers

Marion Griffiths

Age 71

2007 ran a marathon for everydecade of her life

Okinawan Japanese have: more people over 100 years old

per 100,000 population thananywhere else in the world

the lowest death rates fromcancer, heart disease and stroke(the top three killers in the US)

the highest life expectancy forboth males and females over 65

females in Okinawa have thehighest life expectancy in all agegroups
http://longevity.about.com/od/longevity101/p/life_expect.htmhttp://longevity.about.com/od/longevity101/p/life_expect.htm


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Centenarians are 85% Women, Thin

and Doubling in Number Every

Decade

Jeanne Louise Calment 21 February 1875 4 August 1997 122 years, 164 days

Besse Berry Cooper Born August 26 1896 - Alive in Monroe, Georgia, USA


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Frailty Defined, Not Inevitable

A physiologic syndromecharacterized bydecreased reserve andresistance to stressors,

resulting from cumulativedecline across multiplephysiologic systems, andcausing vulnerability toadverse outcomes.

Fried et al. 2003


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Features & Predictors of Frailty

Weight loss 5% bodyweight in last year

Exhaustion

Weakness

Slow walking speed > 6secsto walk 5m

Decreased physicalactivity

Extreme age

Visual loss

Impaired cognition/mood Limb weakness

Abnormalities of gait andbalance

Sedative use

Multiple chronic diseases


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How the Frail Present with Illness

Classical

Silent/Pseudo-silent

AtypicalPresentations Weakness/Fatigue

Falls/Immobility

Cognitive/Mood Change

Dwindles Incontinence

Social Crisis


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Human Growth Hormone

DHEA

Coenzyme Q

Lipoic Acid

Green tea extract

Fish oil

Folic acid

Testosterone, Estrogens and Progesterone

Extreme Caloric restriction

Vitamin and amino acid concoctions to make you look and feel younger and taller


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Growth Hormone Trials in healthy older people

body fat & muscle mass nochange in strength (and SEs ++)

Exercise body fat & musclemass & strength

DHEA Dehydroepiandrosterone Higher levels associated with

longevity in primates and humans

Trials of replacement in rats worked,but not in humans

Caloric Restriction Shown to prolong life in mice,

worms,fish,flies,yeast

No evidence that people live longer

Resveratrol


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Old age isnt so bad when you

consider the alternative


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The Perks to Being >50yrs

No one expects you to run into a burning building.

In a hostage situation you are likely to be released first.

You enjoy hearing about other people's operations.

People no longer view you as a hypochondriac.

You no longer think of speed limits as a challenge.

Your investment in health insurance is finally beginning to pay off.

You sing along with elevator music.

You quit trying to hold your stomach in, no matter who walks into the room.

Your eyes won't get much worse.

Your joints are more accurate meteorologists than the national weather service.

You have a party and the neighbours don't even realise it.

Your supply of brain cells is finally down to manageable size.


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Watkins The American Journal of Clinical

Nutrition 36: OCTOBER 1982, pp 750-758.

The health status of older persons is directly related to thelifestyles they have practiced or which were imposed on themduring infancy, childhood, adolescence and adulthood, as wellas the presence of chronic diseases

Belloc and Breslow 1972 (39) clearly demonstrated thedesirable effect of lifelong devotion to seven good healthpractices. These are, slightly paraphrased:

avoid gluttony, tobacco, and excessive alcohol consumption;

eat nutritionally adequate and regularly scheduled meals;

incorporate into ones lifestyle regularly scheduled hours ofsleep, exercise, and rest and relaxation

MUM WAS RIGHT!


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The most obvious change associated with physiological aging inmature adults is that of personal appearance. The graying hair,the wrinkling skin, the changes in bodily external dimensions,and the almost inevitable resort to prostheses such as eyeglasses and hearing

the gradual diminution of carbohydrate tolerance, the almostlinear decrements in discrete renal functions, the fall in cardiacindex, the diminution in maximum breathing capacity, thedecline of nerve conduction velocity, the reduction in ability totaste and smell, the fall in isoimmunity titers and the rise inautoimmunity titers, and the decrements in muscle strength, tomention only a few parameters.

Many effects deleterious to performance coincide temporallywith aging but are in fact created by the superimposition onphysiological aging of disease processes.


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Fasting blood glucose and blood pH change little; nerve conduction velocity and cellularenzyme activities drop about 15% in a lifetime; cardiac index falls 30%; and vitalcapacity and renal blood flow fall by 50%. However, maximum breathing capacity,maximum work rate, and maximum 02 uptake fall by 60 to 70%. The last mentionedperformances require integrated activity of the cardiovascular, nervous, muscular, andrespiratory systems and show the greatest decrements with age

The variation within a particular age cohort is often nearly as great as the variationamong age cohorts. This leads to the conclusion that in cross-sectional studies, no singleage emerges as the point of sharp decline in function. This observation is particularlyimportant in making decisions in regard to whether a specific person should be forced toretire

Basal metabolic rate (BMR) falls on the average about 20% between ages 30 and 90 asmeasured in cross-sectional studies (27). Since no differences in the ability of thethyroid gland to produce or release thyroxine have been demonstrated (28), other

explanations are required. Fat and connective tissue proportions of the body are knownto increase as total body water decreases with age, though the water content of oxygen-consuming cells does not change significantly. The fall in basal metabolism with age is areflection of the loss of metabolizing tissue with age. Loss of lean body mass, reflectedby the dramatic decrease in body water, is a basic fact of the aging process in man. Thetissue loss is caused by cell death that in turn has numerous causes.


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Energy intake decreases with advancing age. Studies conducted at the GerontologyResearch Center in Baltimore by McGandy et al (32), have shown conclusively that menfrom age 28 onward tend to consume less energy. Simultaneously, they have smallannual reductions in basal energy expenditures. The greatest annual reductions are involuntary activities. Hence, the total heat that must be eliminated in the old issubstantially less than that in the young.

There is substantial evidence to indicate that the response to low or to highenvironmental temperatures is less effective in the old than in the young. As far as coldis concerned, the evidence suggests that older persons can increase their heatproduction as well as the young but that their mechanisms involved in heat conservationare not as effective (33). As far as heat tolerance is concerned, epidemiological studiesof heat stroke indicate that the death rate rises sharply after age 60 (34). The mortalityrate rises with both increasing temperature and with advancing age, suggesting thatdecrements with age occur in heat dissipating mechanisms (35).

These few examples show not only changes in individual organ or metabolic systems butalso support the concept that aging of the total human being is more than thesummation of changes occuring at the cellular, tissue, organ, or single-system level.Human life requires the integrated activity of all organs and systems to cope with thestresses of living. With advancing age, the regulatory mechanisms are less effective.Hence, as persons age, their ability to adapt is diminished (36).

R f D ld M W tki


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References Donald M Watkin

The physiology of aging

27. Shock NW, Yiengst Mi. Age changes in basal respiratory measurements and metabolism in males. J. Gerontol 1955;10:31-40.

28. Baker SP, Gaffney GW, Shock NW, Landowne M. Physiological responses of five middle-aged and el- derly men torepeated administration of thyroid stimulating hormone (thyrotropin; TSH). i Gerontol 1959; 14:37-47.

32. McGsndy RB, Barrows CH ir, Spanias A, Meredith A, Stone JL, Norris AH. Nutrient intake and energy expenditure inmen of different ages. J Gerontol 1966;2 1:581-87

33. Krag CL, Kountz, WB. Stability of body function in the aged. I. Effect of exposure of the body to cold. i Gerontol1950;5:227-35.

34. Driscoll DM. The relationship between weather and mortality in the major metropolitan areas in the 758 WATKIN UnitedStates, 1962-1965. lnt J Biometeorol 1971; 15:23-39.

35. Oechsli FW, Bueckley RW. Excess mortality associated with three Los Angeles September hot spells. Environ Res1970;3:277-84.

36. Shock NW. Systems integration. In Finch CE, Hay- flick L, Brody H, Rossman I, Sinex FM, eds. Hand- book of the biologyof aging. New York: Van Nos- trand Reinhold Co, 1977:639-65.

39. Belloc NB, Breslow L. Relationship of physical health status and health practices. Prey Med 1972; 1:409-2 1.


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Physiology of ageing Review ArticleAnaesthesia & IntensiveCare Medicine, Volume 11, Issue 7, July 2010, Pages 290-292Simon L. Maguire and Benjamin M.J. Slater

Abstract: The impact that ageing has on organisms is acomplex interaction between the processes of ageing at acellular, organ and integrated systems level, and theeffects of environmental factors such as nutrition,infection and trauma. Recovery from an insult that triggers

a pathological response is never complete. Theincremental fall in possible performance is part of theprogressive diversity in physiology that is the truehallmark of ageing. In this article we will outline some ofthe physiological changes, particularly cardiorespiratory,associated with the ageing process that will be of relevanceto anaesthesia.

Theories of ageing, Respiratory system, Cardiovascularsystem, Exercise, Energy and temperature regulation,Summary, References
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