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more remote systems, mimicking the mosaic of presenting symptoms in frailty. With continued lack of physical activity, additional systems failures are inevitable as the toxic mix of inactivity and factors such as poor diet, pain, depressive symptoms, cognitive dysfunction, and fatigue negatively impact and distort the trajectory of the inherent ageing process. The parallels that exist between frailty and exercise deficiency can be seen in the unpredictable presentations and variation of symptomology that can occur. Because of the tenuous links between the value of a physiological function and a specific age, it can be predicted that the degree of exercise deficiency in each individual, rather than their chronological age, will be better correlated to clinical outcomes. Similarly, because of the inherent heterogeneity, the length of time an individual has been sedentary may not correlate with severity of symptoms.¹⁹ The most important physiological changes associated with ageing or disuse that impact exercise capacity are presented in Tables 7.1–7.4. In most physiological systems, the normal ageing processes do not result in significant impairment or dysfunction in the absence of other pathology and under resting conditions. However, in response to a stressor or prolonged and profound disuse, the age‐related reduction in physiological reserves (homeostenosis) may result in difficulty completing a task requiring near‐maximum effort. This could be as ‘simple’ a task as rising from a chair, which may exceed the hip and knee extensor strength of a frail octogenarian, for example.

Table 7.1 Changes in exercise capacity due to ageing or disuse, potentially modifiable by physical activity.

Component of exercise capacity	Effect of ageing or disuse
Maximal/peak aerobic capacity	Decrease
Tissue elasticity	Decrease
Muscle strength, power, endurance, coordination	Decrease
Oxidative and glycolytic enzyme capacity, mitochondrial volume density	Decrease
Gait speed, step length, cadence, gait stability	Decrease
Static and dynamic balance	Decrease

Table 7.2 Changes in cardiorespiratory function due to ageing or disuse, potentially modifiable by physical activity.

Cardiorespiratory function	Effect of ageing or disuse
Heart rate and blood pressure response to submaximal exercise	Increase
Maximal heart rate	Decrease
Resting heart rate	No change
Maximal cardiac output, stroke volume	Decrease
Endothelial cell reactivity	Decrease
Heart rate variability	Decrease
Maximal skeletal muscle blood flow	Decrease
Capillary density	Decrease
Arterial distensibility	Decrease
Vascular insulin sensitivity	Decrease
Plasma volume, haematocrit	No change, decrease
Postural hypotension in response to stressors	Increase
Total lung capacity, vital capacity	Decrease
Maximal pulmonary flow rates	Decrease

Table 7.3 Changes in metabolism and body composition due to ageing or disuse, potentially modifiable by physical activity.

Metabolic/body composition change	Effect of ageing or disuse
Resting metabolic rate	Decrease
Total energy expenditure	Decrease
Thermic effect of meals	Decrease, no change
Total body water	Decrease
Total body potassium, nitrogen, calcium	Decrease
Muscle mass	Decrease
Fat mass, visceral fat, intramuscular fat/connective tissue	Increase
Bone mass, density, tensile strength	Decrease
Protein synthesis rate, amino acid uptake into skeletal muscle, nitrogen retention, protein turnover	Decrease
Gastrointestinal transit time	Increase
Appetite, energy intake	Decrease, no change
Glycogen storage capacity, glycogen synthase, GLUT‐4 transporter protein content and translocation to membrane, oxidative and glycolytic enzyme capacity	Decrease
Lipoprotein lipase activity	Decrease
Total cholesterol, LDL cholesterol	Increase
HDL cholesterol	Decrease, no change
Hormonal and sympathetic nervous system response to stress	Increase
Growth hormone, IGF‐1a	Decrease
Heat and cold tolerance, temperature regulatory ability	Decrease

      LDL, low‐density lipoprotein; HDL, high‐density lipoprotein.

      ^a Most training studies show no change in growth hormone or circulating IGF‐1, although tissue levels of IGF‐1 may increase.

Table 7.4 Changes in the central and peripheral nervous system due to ageing or disuse potentially modifiable by physical activity.

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Function	Effect of ageing or disuse