Ageing and physiological functions.

In youth, most physiological functions have generous spare capacity. Even in health, however, increasing age is characterized by progressive erosion of these 'safety margins'. Examples include the decline of bone mass (towards a threshold for likelihood of fracture), of glomerular filtration rate (towards a threshold for susceptibility to clinical renal failure), of renal tubular function (towards a threshold for clinically important susceptibility to dehydration), of hepatic function (towards a threshold for accumulation following conventional 'young adult' doses of common medications), or of lower limb explosive power (towards thresholds for impaired functional mobility). Increasing age is also characterized by a rising prevalence of chronic pathologies, complicating attempts to determine the rate or the mechanism of the age-related decline in a physiological function. Nevertheless, it is clear that in many organs the loss of function is largely attributable to the loss of functioning cells, even in the absence of overt disease. This apparently fundamental aspect of ageing remains poorly understood.