Dementia/cognitive decline is another emerging epidemic without a pharmacologic cure in which treatment of mild cognitive impairment with robust exercise is effective compared to gentle stretching and toning exercise. Importantly, cognitive gains are proportional to strength improvements.4,24 highlighting the need for prescriptions that are concordant with potential anabolic pathways beneficial for both neural and muscular function. Therefore, it is vital to promote healthy and dignified ageing by helping healthcare systems more efficiently implement evidence‐based programmes for frail older adults in all community and aged care settings.
Inter‐individual variability in response to exercise (non‐responder phenomenon)
Dose‐response relationships between changes in fitness and better health outcomes have been defined for some, but certainly not all, diseases and syndromes. Some modalities or doses of exercise promoted for older adults (mild callisthenics, slow‐paced walking) have little or no discernible effects on physical fitness but may yield benefits in some domains. This area of investigation is critical for defining threshold and optimal levels of activity that are necessary for health promotion and disease management. It should be recognised that what is suitable for prevention may be entirely inadequate for treatment, as is also the case with pharmacological management of chronic diseases. For example, aspirin may reduce the risk of ischaemic heart disease, but a host of potent agents and surgery may be required once coronary occlusive disease is present and symptomatic.
Dose‐response heterogeneity is not unique to pharmaceutical therapies.25 In the era of precision medicine, interindividual variability in the magnitude of response to supervised exercise training (subject‐by‐training interaction or individual response) has received increasing scientific interest in both adults and children.26‐31 For instance, some individuals show improvements with exercise training (e.g., decrease in fasting glucose) and are considered responders, whereas others may not have such a response (e.g., no change or even increases in fasting glucose) and are considered non‐responders.32 A physiological non‐response to exercise in one outcome does not signify a non‐response in all outcomes. Exercise and medical researchers have recognised the substantial variability in patient response to physical exercise interventions and have sought to understand these differences. Individual interaction of physiological, molecular (i.e., genetics, epigenetics, transcriptomics, and metabolic factors), and environmental factors are being investigated as potential mediators of the lack of a response to exercise in some participants.33
Does exercise increase life expectancy?
The effects of exercise on total mortality are unlikely ever to be substantiated via randomised controlled clinical trials, given the impossibility of random assignment to various physical activity regimens over many decades. However, there is clear evidence of an inverse, linear dose‐response relationship between the volume of physical activity reported in epidemiological studies (with sample sizes ranging from fewer than 500 to over 2.5 million individuals) and all‐cause mortality rates.1 These relationships are demonstrable for both men and women and for both older and younger adults. Volumes of energy expenditure during exercise of at least 1000 kcal per week reduce mortality by about 30%, whereas reductions of 50% or more are seen with volumes closer to 2000 kcal per week, when more precise measures or estimates of physical activity participation incorporating fitness assessments are utilised instead of surveys. These changes in all‐cause and cardiovascular mortality translate to an increase in life expectancy of ~2 years for those exercising at such volumes. In a recent example, in a cohort study of 16,741 women with a mean age of 72, women who averaged approximately 4400 steps/day had significantly lower mortality rates during a follow‐up of 4.3 years compared with the least active women who took approximately 2700 steps/day. More steps taken per day were associated with lower mortality rates until approximately 7500 steps/day.34
Despite the consistency of the data from well‐designed observational studies, many questions remain regarding the minimum threshold for efficacy; the effect of exercise intensity, duration, and frequency (apart from contributions to overall volume); the effect of non‐aerobic modalities of exercise; and the mechanisms of benefit. From a public health perspective, if small, effective doses of moderate‐intensity activity are found to be as beneficial as longer bouts of vigorous activity, adoption of mortality‐reducing physical activity recommendations by sedentary middle‐aged and older adults may be more successful. Of particular relevance to the exercise prescription for this cohort are studies that have demonstrated that a change from a sedentary to a more active lifestyle in midlife or beyond is associated with a reduction in mortality. In the sections that follow, the focus is on changes in functional capacity, physical fitness and body composition, quality of life, and disease burden, rather than on changes in longevity itself. It is in these domains that the centrality of physical activity patterns to optimal ageing is perhaps most relevant to the concerns of the healthcare professional and the older individual.
Physical function as a biomarker of healthy ageing and objective of exercise programmes
Physical function (i.e., characteristics such as aerobic capacity, gait speed, balance, mobility, and muscle strength) is currently being proposed as a biomarker of healthy ageing in humans, predictive of adverse health events, disability, and mortality, in addition to tools commonly used as functional outcomes for clinical trials.35 Recently, Ramirez‐Vélez et al.36 showed that older adults with handgrip strength greater than the muscle weakness thresholds had lower odds of adverse events in most of the intrinsic capacity domains, as well as a lower hospitalisation rate (in men) than their weaker peers, adjusted for disease burden. Thus, multi‐morbidity, including cardiovascular disease, is not the most important factor modulating individual domains of intrinsic capacity (i.e., cognition and mental health, sensory function, metabolic rate, mobility, and muscle strength) responsible for functional decline and diminished ability to perform activities of daily living (ADLs). Moreover, physical performance measures, such as gait speed, predict mortality in older adults better than chronic diseases (e.g., hypertension), and preservation of functional capacity is now a primary focus for clinicians in the management of cardiovascular diseases, for example.37,38 For these reasons, functional ability‐ retaining autonomy and independence as people age‐ is the cornerstone of healthy ageing, a term established by the WHO in its first world report on ageing and health.39
From a clinical point of view, frailty has emerged as one of the most relevant clinical syndromes in geriatric medicine. This term relates to a distinctive ageing‐related health state in which multiple body systems gradually lose their in‐built capacity, resulting in decreased physiological reserves and resilience in the face of stressors.40,41 Over the last few years, it has attracted increasing interest due to its direct relationship with adverse health effects such as physical and functional decline, institutionalisation,42,43 disability, hospitalisation, poor quality of life, excess morbidity, and increased mortality.44 Accordingly, an important conceptual idea for frailty is that the focus should be on functionality rather than the diagnosis of disease for older patients. Thus, improving or maintaining function becomes the ultimate mission for the medical care of older people. In addition, it has been shown that the best strategy is to prevent functional decline instead of trying to recover function once it has been lost.5,45
Preserving exercise capacity with age via an active lifestyle
There is a great similarity between the physiological changes attributable to disuse and those typically observed in ageing populations, leading to the speculation that the way we age may be modulated with attention to activity levels.46 As previously stated,19 the detrimental effects of exercise removal (such as enforced bed rest) on these physiological systems can be compared to the symptomatology presented by patients with diagnosed frailty. As the benefits of exercise affect a broad range of physiology, exercise deficiency will affect systems traditionally thought of as being exercise‐dependent