Aging/senescence

Abstract

With increasing age, cellular senescence and physiological dysregulation proceed, reducing somatic resilience, increasing frailty, and leading to increased physical disability, morbidity, and mortality. By promoting variability in somatic outcomes, developmental processes and environmental and ecological settings set the stage for senescent biology and variable lifespans. Early life adversity forces organisms to expend more physiological capacity resisting stressors, while environments limiting stressor exposures promote greater physiological reserve and resilience. At reproductive maturity, somatic resources are reallocated toward reproductive effort. Individual and familial patterns of morbidity and longevity attest to genetic influences on lifespan, but few specific alleles and haplotypes are associated with human lifespan. Stressor exposures are a major contributor to age‐related losses of functional abilities (frailty) and physiological dysfunction (allostatic load). Reduced physical activity at older ages promotes osteopenia and sarcopenia, twin biomarkers of frailty, and frailty indices reflect age‐related senescent losses. Age‐related physiological dysregulation and frailty are inherent to living systems as life cannot simultaneously optimize all physiological functions, protect their somas from all environmental insults, and still be reproductively successful.