A decline in physiological reserve has been observed in older members of the population. Whether this decline is a truly physiological change can be debated. The majority of the data that have informed our understanding of the changes that are associated with age and ageing originate from cross sectional studies in which individuals of different ages are compared in terms of average function for their chronological cohort.

This approach shows a consistent trend for gradual decline in the function of different organs with advancing age. A few studies that have followed cohorts of people longitudinally as they age have shown differing results.¹ For example, cardiac function in older people free of heart disease does not show inevitable decline with age.² Degenerative changes that may be considered a part of this expected or “normal” decline with advancing age, for example the decline in bone mineral density commonly observed throughout adult life becomes pathological and is termed osteoporotic at a certain threshold.³ It is consequently very difficult to make a clear distinction between normal physiological ageing and disease.

It is clear that heterogeneity exists within the elderly population and within the organ systems of the same individual. This has been increasingly recognised and has led to an appreciation of differing potential outcomes of the ageing process. In recent years there has been greater attention directed to active, healthy older people as models of healthy or successful ageing.⁴

Further reading: Top tips for healthy ageing – it’s never too late

What is normal ageing?

Although we lack precise knowledge of what constitutes the normal ageing process, a consistent physiological decline is seen with advancing age and will affect a large proportion of the people found within a geriatrician’s patient group. Pragmatically a geriatrician must have a knowledge of these changes to advise appropriate preventative strategies, provide accurate, prompt diagnoses and advise suitable interventions for disease in order to gain the best possible outcomes for their patients.

A knowledge of the biology of ageing is important in avoiding the dismissal of treatable pathology as an inevitable consequence of older age, or conversely treating normal ageing processes as if they were disease, creating possibilities for iatrogenic harm.

Some of the different aspects of clinical care that can benefit from the application of physiology into clinical practice will be further expanded and illustrated by the use of relevant examples throughout the course of this paper.

Life expectancy

Modern medicine in the developed world has achieved success by increasing life expectancy, but a large number of the elderly population will spend their latter years affected by ill health and disability.⁵ A central future goal for modern medicine and for our wider society will be to reduce the number of years a person can expect to live in ill health, both to improve quality of life at the level of the individual, but to reduce the economic burden of providing health and social care to a large, and unhealthy aged population.

Studies on longevity in twins have suggested that the genetic contribution to life span and possibly the process of ageing itself is relatively small, and as such external factors have an important impact on the ageing process.⁶

Ageing well

Primary prevention

Primary prevention of disease has proved difficult to put into practice, with only 4% of Americans currently estimated to follow the well publicised basic healthy living rules of maintaining a healthy weight, not smoking, exercising regularly, and eating five portions of fruit and vegetables a day.⁷

A geriatrician who has a knowledge of the factors that are encountered throughout the life course of an individual that increase the likelihood of greater physiological reserve in older age is in an excellent position to promote education and intervention in younger adults that may allow the avoidance of disability and disease in older age. This will add quality to the additional years of life expectancy modern medicine has achieved.

The potential success of such an approach can be appreciated by considering exercise as an example of the five basic rules for healthy living described above. Exercise has been shown to facilitate maintenance of cardiovascular function and reduces many of the risk factors associated with heart disease, diabetes and cancers.

In addition, other changes associated with ageing that were once thought to be inevitable consequences of the ageing process which include sarcopenia, loss of bone density and postural stability can be positively counteracted through physical exercise.⁸ In a recent review of longitudinal epidemiological studies evaluating the possible effect of physical activity and cognitive decline or dementia, there is a suggestion of a concurrent protective effect of exercise on cognitive decline.⁹

Increasing levels of recruitment to a more active lifestyle in younger people, could make a significant difference to healthy life expectancy in later life.

In addition to adding value to the efforts a geriatrician may make in promoting healthier ageing on a population level, a knowledge of the biology of ageing can be usefully applied in the first recognition of disease in older patients.

Immune response

Elderly people can often present atypically in comparison to younger adults, with alterations in the nature and intensity of presenting symptoms due to the older body’s physiologic inability to respond adequately to stress.

An attenuated immune response in advanced age has been well illustrated by the patterns of morbidity and mortality witnessed during influenza outbreaks, where most of the significant morbidity and mortality occurs in older people.^10,12 Advancing age itself has been identified as a risk factor for the more severe complications of influenza, acting independently of comorbidity status.^11,12 This also applies to other infectious diseases including those which are hospital acquired.

The changes seen in the immune system of older people include the reduction in the overall proportion and efficacy of “naïve” T cells as the function of the thymus gland declines with age. The ability of the adaptive immune system is affected negatively in terms of reduced production of “memory” T cells with the presentation of new antigens, and those cells that are produced are less efficient than those produced in the same individual earlier in life.¹²

Influenza also provides an example of where it is important for a geriatrician to understand age-related physiology in the context of health promotion for the elderly population. The efficacy of vaccination in older people has been observed to be lower than that in younger members of the population.¹²

However, it remains important for a geriatrician to promote vaccination in the elderly, as studies confirm that vaccination for influenza reduces the risk for pneumonia, hospitalisation and death in this group. The efficacy of the influenza vaccine is lower in elderly people. This occurs as a consequence of the changes to the ageing immune system described in the previous paragraph. Efficacy for preventing influenza- like illness has been estimated at 35% in one study of nursing home residents who received the vaccine.¹³ As such, it is important to promote the vaccination of healthcare workers who work with elderly people to reduce exposure to the virus among hospital inpatients and residents of care homes.

In a recent Cochrane review article, evidence for the efficacy of immunising healthcare workers was described as limited in terms of reducing laboratory proven cases of influenza. However, there was some suggestion of impact on influenza-like illnesses and remains an important public health strategy.¹⁴ Uptake of the vaccine among frontline healthcare staff is relatively poor, the Department of Health published figures regarding uptake of the seasonal influenza vaccine among healthcare workers in 2010/2011. The overall uptake of the vaccine by frontline staff was 34.7% during this time period.¹⁵

Surveys conducted in healthcare workers have shown that workers who do not get vaccinated do not perceive themselves at risk, have doubts about the efficacy of influenza vaccine, often have concerns about side effects, and occasionally do not perceive their patients to be at risk of infection with the influenza virus. Clearly, this is an example of where a geriatrician with a good understanding of the changes seen in the ageing immune system could be in a good position to provide education to colleagues to increase participation in work- based vaccination programmes.¹⁴

The promotion of functional independence and of strategies to maximise physiological competence are within the remit of every practising geriatrician. It is an important part of a geriatrician’s role to promote the appropriate treatment of disease and protect their patients from therapeutic nihilism.

Ageing and sarcopenia

Sarcopenia, the syndrome of loss of muscle mass with advancing age provides a good example of where a knowledge of the physiology of ageing allows prevention, along with identification and intervention for a common syndrome, which can threaten an individual’s functional competence but can commonly be accepted as a normal part of ageing for which no intervention will be effective.^8,16

Muscle mass and strength is seen to decline from the fourth decade of life and accelerates after the onset of old age, the rates of decline are higher in individuals with sedentary lifestyles. Inactive adults see a faster and much greater loss of muscle mass when compared to physically active subjects. A decrease in muscle strength, begets reduced levels of activity that in turn leads to further loss of muscle strength, setting in motion a downward spiral that ultimately leads to functional decline. A loss of muscle strength and mass negatively impacts on an individual’s ability to perform household tasks and maintain independence. Poor muscular support can lead to postural instability, and falls and reduced muscle strength can facilitate the onset, and impact on the severity of osteoarthritis.⁸

This loss of muscle mass is thought to be due to a number of risk factors, including low physical activity and poor diet along with hormonal changes such as insulin resistance, declining growth hormone levels, and changes in circulating cytokine levels.⁸

In addition to the muscle fibre loss, the spinal innervation that regulates muscular activity is reduced. The process predominantly affects the fast twitch fibres involved in anaerobic exercise and as such can affect people who have been physically active throughout their life. It is thought that the loss of spinal motor neurons is the primary step in the process, when a motor neuron is lost a neighbouring motor neuron, which is usually of the slow twitch variant may aid the muscle and prevent atrophy. However the slow twitch muscle, which now forms a greater proportion of total muscle mass, has a slower rate of contraction and the individual affected will experience a globally slower speed of muscle movement and loss of balance with advancing age.^8,16

Pharmacological treatment with growth hormone has been studied; these studies have reported that growth hormone replacement has not consistently been effective in increasing muscle mass and strength in older people.⁸

However, resistance training, has been found to be efficacious in reversal of sarcopenia. Muscle mass, strength and muscle quality are reported to improve significantly with resistance training in older people, even in the frail elderly.⁸

A lower rate of protein synthesis has been demonstrated in elderly people participating in studies evaluating the effect of certain nutrients on the process. These studies suggest that nutrients activate protein synthesis much less in old muscles than in young ones. In malnourished elderly persons, poor protein is a barrier to gains in muscle tissue and strength from interventions such as resistance training. Increasing protein intake in the elderly and especially frail elderly can minimise the sarcopenic process.⁸

This provides a good example of a physiological process observed in ageing, that is amenable to a low cost intervention if it is recognised and treated appropriately with significant effects on the functional ability and wellbeing of the patient concerned.

Polypharmacy in the ageing patient

A geriatrician must be able to prevent iatrogenic harm from prescription medication and from other medical interventions that may interact with the differing physiology seen in advancing age.

A prescription for a number of medications is common in later life, often appropriately and prompted by compliance with evidence-based guidelines for the management of the chronic diseases which are prevalent within older populations. However, ageing is associated with physiologic changes that affect how medications are handled, including alterations in volumes of drug distribution, drug absorption, metabolism and clearance.

Elderly patients may also have increased or decreased drug responsiveness due to differences in receptor effects. These pharmacokinetic and pharmacodynamic effects may result in a prolonged half life of medications, increased potential for drug toxicity and a greater likelihood for adverse drug reactions.¹⁵

Adverse drug reactions are common, it is estimated that up to 35% of community dwelling older adults and over 50% of nursing home residents experience at least one adverse drug event per year. Adverse drug reactions are a common cause of older people being admitted to hospital, estimates suggest that 5% to 20% of hospital admissions are attributable to an adverse drug reaction.^17,18,19

It has been observed that even after correcting for drug dosing or administration errors, including poor compliance and therapeutic failures, the overall incidence of serious adverse drug events was still significant at 6.7% among a population of hospital inpatients in the USA and were thought to be likely to be secondary to physiological changes found within the elderly population studied.²⁰

The majority of adverse reactions in older people are predictable type A reactions i.e. they are attributable to a predictable accentuation of the known pharmacological effect of a drug. These can occur due to physiological changes in pharmacodynamics and pharmacokinetics in older age. However, adverse reactions can occur due to drugs interacting with biological changes associated with ageing eg. orthostatic hypotension may be more pronounced in the older person prescribed diuretics.¹⁹

Type A adverse drug reactions are usually avoidable and typically involve commonly prescribed medications such as anticoagulants, non-steroidal antinflammatory drugs, digoxin, diuretics, hypoglycaemics and vasodilators.^18,19

Older patients consume on average five prescription medications per day, thereby increasing the risk of drug-drug and drug-disease interactions. The number of prescribed medications a patient has is exponentially linked to the risk of adverse drug reaction.^18,19

Knowledge of pharmacological principles and how the physiology of ageing can impact on drug handling is useful if a geriatrician is to promote the appropriate use of medication for the treatment of disease while minimising the risk of iatrogenic harm.

The understanding of adverse drug reactions as clinically important causes of morbidity and mortality will alert the geriatrician to the possibility of an adverse drug event as the cause for a patient’s presentation to medical services, therefore allowing early treatment and minimising harm. It will also allow the geriatrician to promote patient safety by reporting possible adverse reactions in this patient group, who are often not well studied in major drug company sponsored randomised control trials.

Conclusion

In conclusion, a knowledge of the biology of ageing is useful to the clinical practice of geriatric medicine for a number of key reasons.

The geriatrician, by understanding the mechanisms in which the ageing body may fail to respond to stress due to ill health adequately, may be able to better diagnose illness where it presents atypically, and provide prompt and anticipatory care for patients whose illnesses may follow a more severe course than would be seen in younger, or more physiologically competent patients.

An understanding of how ageing biology impacts on the pharmacokinetics and pharmacodynamics of prescribed medications can allow the prescribing process to be better informed, adverse drug reactions better avoided, and more readily recognised where they occur.

A geriatrician has a role in promoting health and wellbeing in the older population they serve, but also have a wider role in the education of the general population to promote healthier lifestyles throughout the life course, which will lead in turn to more successful, healthier ageing.

Conflict of interest: none declared

References

Kane R, Ouslander J, Abrass I. Essentials of Clinical Geratrics. 5th ed. New York, McGraw Hill, 2004
Lakatta EG, Changes in cardiovascular function with aging. European Heart Journal 1990; 11 Suppl C: 22-9
Francis R. Metabolic Bone Disease in Fillit H, Rockwood K, Woodhouse K Eds, Brocklehurst’s Textbook of Geriatric Medicine and Gerontology. 7th ed, Phillidelphia, Saunders Elsevier 2010; 553-56
Rowe JW, Kahn RL. Human aging, usual and successful. Science 1987 237:143-49
Fries JF. Aging, natural death and compression of morbidity. New England Journal Medicine. 1980; 303 (3): 130-35
Jungquist B, Berg S, Lanke J, et al. The effect of genetic factors for longevity: a comparison of identical and fraternal twins in the Swedish twin registry. Journal of Gerontology 1998; 53 (6): 441-46
Reeves MJ, Rafferty AP. Healthy lifestyle characteristics among adults in the United States, 2000. Archives Internal Medicine 2005; 165: 854-7
Navazio. F, Testa. M Benefits of Physical Exercise in Timiras. P. Ed. Physiological Basis of Aging and Geriatrics. 4th ed. New York, Informa Healthcare, 2007: 381-90
Rolland Y, Abellan van Kan G, Vellas B. Physical Activity and Alzheimer’s Disease: from prevention to therapeutic perspectives. JAMDA 2008; 9 (6): 390-405
Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiology Review 1982; 4: 25-44
Barker WH, Mullooly JP. Impact of epidemic type A influenza in a defined adult population. American Journal of Epidemiology 1980; 112(6): 798-811.
Tummala M et al. Clinical Immunology: Immune Senescence and the Acquired Immune Deficiency of Aging in Fillit.H, Rockwood. K, Woodhouse. K Eds, Brocklehurst’s Textbook of Geriatric Medicine and Gerontology. 7th ed, Phillidelphia, Saunders Elsevier 2010; 553-56
Thomas RE, Jefferson T, Lasserson TJ. Influenza vaccination for healthcare workers who work with the elderly. Cochrane database of systematic reviews. 2010 Feb 17;(2):CD005187
Department of Health. Seasonal Influenza Vaccine Uptake amongst frontline healthcare workers in England 2010/11. [cited 2012 Nov 12]. Available from: http://www.dh.gov.uk/en/Publicationsandstatistics
Mangoni A, Jackson S. Age Related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. British Journal of Clinical Pharmacology 2004; 57: 6-14
Doherty TJ, Invited review: Aging and Sarcopenia. Journal Applied Physiology, 2003; 95 (4):1717-27
Gallagher P, O’Mahony D. Inappropriate prescribing in older people. Review of Clinical Geronotology 2008; 18:16-76
Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18820 patients. BMJ 2004; 329(7456): 15-19
Gallagher P, Prescribing in Older People in Gosney. M, Harper.A et al Eds. Oxford Desk Reference Geriatric Medicine. Oxford. Oxford University Press.2012. 44-45
Lazarou J, Pomeranz B, Corey, P. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. Journal of the American Medical Association 1999, 279, 1200-1205

The biology of ageing