The progressive decline in physiological function and homeostatic capacity that occurs as an organism ages, leading to increased vulnerability to disease and mortality. This intrinsic biological process reflects the cumulative impact of molecular and cellular damage over time, affecting multiple organ systems including the endocrine axis. Clinical manifestations often involve hormonal imbalances, reduced metabolic efficiency, and impaired tissue repair mechanisms, significantly contributing to the overall burden of senescence.
Origin
The term combines ‘age-related,’ indicating a correlation with advancing chronological time, and ‘dysfunction,’ stemming from the Latin dys- (bad, difficult) and functio (performance). It is a concept central to gerontology and the study of human longevity, providing a clinical framework for understanding senescence. Within endocrinology, it refers specifically to the declines in hormone production and sensitivity seen in conditions like somatopause and andropause.
Mechanism
Mechanistically, age-related dysfunction is driven by cellular senescence, mitochondrial decline, telomere shortening, and chronic low-grade inflammation, often termed inflammaging. These underlying cellular processes disrupt critical endocrine feedback loops, impairing the synthesis, transport, and receptor binding of key hormones. The resulting dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) and Hypothalamic-Pituitary-Gonadal (HPG) axes contributes significantly to the observed systemic decline and loss of resilience.
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