Although old age is readily recognizable, methods to define and measure the underlying biological processes are much less amenable to study. For this reason, life expectancy has been widely used as a surrogate measure of ageing, as well as to monitor economic progress at national and regional levels. It is generally acknowledged that lifespan is a constitutional feature of the human phenotype, and twin studies have indicated that 25–33 per cent of the variance in human longevity is genetic in origin. External factors including lifestyle can also exert a major influence, as illustrated by the current mean life expectancies of 79 and 86 years for males and females in Japan, whereas the comparable figures for Botswana are 35 and 33 years, respectively. The importance of genetic inheritance as a determinant of extended survival has been illustrated by population level studies in Okinawa, an island prefecture of southern Japan with a very high prevalence of long-lived individuals. On the island, the mortality rates of the male and female siblings of centenarians were approximately half those of birth cohort-matched, non-centenarian siblings. These findings parallel an earlier study of the family of Jeanne Calment, who died in France in 1997 aged 122 years. Of her 55 relatives, 24 per cent had lived to >80 years compared to just 2 per cent of a matched control group. However, it remains unclear whether the enhanced lifespan of individuals who exhibit above average longevity is due to a slowing of the overall ageing process or is primarily associated with resistance to major life-threatening pathologies. The concept of an ‘allostatic load’, potentially involving the neuroendocrine, sympathetic nervous, immune and cardiovascular systems, and metabolic pathways, has been advanced to describe the lifetime costs of adapting to physical and psychological stresses. According to this hypothesis, while the actions of biological mediators of stress can be initially beneficial to health, chronic stimulation results in regulatory imbalance and subsequent pathophysiological changes. Empirical studies have indicated increased physiological dysregulation and functional decline at >70 years of age, which would imply that predicted global increases in the numbers of older persons will be accompanied by disproportionately larger groups of individuals with major age-related pathologies.
Sex Differences in Age Trajectories of Physiological Dysregulation: Inflammation, Metabolic Syndrome, and Allostatic Load
