Ageing is widely seen as the result of lifelong accumulation of random molecular damage². Damage results in declining function at many levels³, including in mitochondrial function, DNA transcription (through unrepaired somatic DNA mutations) and in the ability of cells to divide and repair tissues. The balance between damage and repair mechanisms determines the amount of unrepaired damage, which manifests as ageing at the cellular and organism level. Secondary responses to damage can then occur, including chronic inflammation, hypothesized as a major element in human ageing⁴.

Ageing processes are surprisingly plastic and variable. This is evident at all levels from the molecular to the societal and global population levels. The most dramatic demonstration of the plasticity of ageing is the finding that hundreds of mutant genes (mainly knockouts) can produce radical life extensions in model organisms⁵. In addition to affecting stress responses and telomeres, endocrine signalling has also emerged as particularly important in these models. In general, the impact of ‘longevity’ gene manipulation on lifespan becomes progressively smaller on moving up the evolutionary ladder⁶ and relevance to human ageing is speculative.

In addition to genetic manipulation, caloric restriction in laboratory settings also increases lifespan when compared to unlimited feeding^7,8. In humans, obesity is a risk for mortality and functioning in older people⁹ but whether there are benefits in radically reducing caloric intakes below those required for maintaining a healthy weight is unclear.

The variability of ageing in humans is apparent both in single organs and in the longevity and functioning of individuals. Analyses of the Baltimore Longitudinal Study of Ageing have shown marked heterogeneity in the rates of decline in function of different organ systems: for example, mean maximum work rate and renal blood flow generally decline far faster than measures of nerve conduction¹⁰. More surprising, individuals show great heterogeneity in patterns of impairment of individual systems, with little indication of typical patterns. In human population studies, it is usual to find people functioning at a higher level than others aged 20 or 30 years younger.

One potential means of identifying an individual’s ‘true’ age is through identifying biomarkers of ageing. The concept of biomarkers of ageing is appealing because it implies biological measures can reflect the rate of ageing and that successful interventions on the ageing process may affect these markers. The American Federation for Aging Research proposed that a biomarker of ageing must¹¹:

• predict the rate of ageing – i.e. it should be a better predictor of lifespan than chronological age;
• monitor a basic process that underlies the ageing process, not the effects of disease;
• be testable repeatedly without harming the person;
• be valid in humans and in laboratory animals.

Markers showing potential include telomere length¹²and p16^INK4a expression¹³.

The search for biomarkers of ageing assumes there is an underlying biological state of ageing that can be summed up as a single number but counterarguments regard ageing as a complex, uncoordinated phenomenon that cannot be encapsulated so simply¹⁴. Despite much research effort, most gerontologists accept that no biomarkers of ageing have yet been validated^11,15.

A key aspect of functional ageing or functional health status assesses functioning at the level of the whole older person. Functional health status is related to chronological age, disease and need for care, and understanding the functional aspects of ageing is an important part of geriatric medicine. In the medical model of disease, the clinician gathers symptoms and signs, makes a diagnosis and bases the therapeutic approach on this diagnosis. Complementing this disease-orientated approach, functional assessment provides an understanding of the impact and consequences of the older person’s disease or diseases, giving information on level of independence and prognosis, as well as health care, rehabilitation and social needs.

Since a major impact on functional health comes from disease, a framework that represents the relationship between disease and disability is valuable in developing the concept of functional ageing. The World Health Organization (WHO) originally proposed a theoretical pathway progressing from disease to impairment to disability to handicap¹⁶. An alternative pathway, proposed by Nagi¹⁷ and utilized by the US Institute of Medicine¹⁸, progresses from diseases and conditions to impairment to functional limitation to disability. An effort to operationalize this latter pathway defines ‘impairment’ as dysfunction and structural abnormalities in specific body systems, ‘functional limitation’ as restriction in basic physical and mental actions such as ambulating, grasping, and stepping up, and ‘disability’ as difficulty in doing activities in daily life such as personal care, household management, job and hobbies¹⁹. The importance of identifying external factors that needlessly cause disablement outside the individual is a major theme in the more recent WHO classification systems²⁰.

Means of assessing and reporting functional health status include the following.

Self-Reported Functioning

Physical functioning shows a downwards trend with age and is often assessed through self-report of the ability to perform specific tasks, including self-care activities such as bathing and dressing (activities of daily living), and activities necessary to maintain independence in the community, such as shopping and food preparation (instrumental activities of daily living)^21-24. A concern with self-reported functioning is that different individuals and groups may have different thresholds for reporting difficulty or inability to carry out activities²⁵.

Performance Measures

Performance measures of functioning, in which the individual is asked to carry out standardized tasks, offer a way of benchmarking function and comparing over time or across populations²⁶. Selfreported functional status may differ from measured function for a variety of reasons, including differences in the domains measured. Assessing both allows us to combine an objective measure of poor performance with an indication of how much everyday function is affected²⁷. Tests of physical function are used in clinical assessments of older people^28,29 and can help identify individuals with pre-clinical limitations who are at increased risk of developing disabilities^30,31. One established measure is the short physical performance battery, including measures of gait speed, chair stands and tandem balance tests: this score has been widely used in clinical settings for the assessment of mobility limitations³². Other approaches include these measures plus muscle strength and respiratory function³³.

Frailty

Frailty, generally taken to mean multisystem impairment and a high level of vulnerability, has been defined in two ways: as a phenotype; and as a score of age-related deficits or ‘frailty index’. The phenotypic approach defines frailty as a clinical syndrome in relation to five criteria: unintentional weight loss (10 lbs or more in the preceding year); self-reported exhaustion; weakness (grip strength); slow walking speed; and low physical activity³⁴. Using these criteria, individuals are defined as either frail (three or more criteria present) or not frail (fewer than three criteria). The frailty index approach sums the number of age-associated deficits experienced by an individual, including symptoms, signs, diseases and disabilities³⁵ (Rockwood 2007). The resulting score provides an indication of the likelihood that frailty is present, and the index demonstrates characteristic changes with age. Each of these operationalizations of frailty has been validated in multiple populations. Although the two approaches overlap there are substantial differences between them³⁶ and it has been suggested each represents a different form of frailty and a different trajectory of age-related loss of function³⁷.

Cognitive Function

Age-related functional decline has cognitive as well as physical aspects. These often occur together, and they share some risk³⁸ as well as protective³⁹ factors. The care burden associated with dementia, on both a societal⁴⁰ and a household level⁴¹ level, is large. There are major public health concerns about the impact on health and social care services of growing numbers of older people with declining cognitive function and dementia⁴². Among the challenges of dealing with this growing problem is the shortage of effective treatments for dementia, and attention has been drawn to identifying individuals with mild cognitive impairment – that is, those who are not demented but have a memory impairment beyond that expected for age and education⁴³. Cognitive function and dementia are covered in more details in Part IV of this book.

Factors Affecting Functional Health Status