Cortisol (serum/salivary)

Cortisol is the primary glucocorticoid of the adrenal cortex, the end-effector of the hypothalamic–pituitary–adrenal (HPA) axis. It follows a pronounced diurnal rhythm: levels surge 50–160 % within 30–45 minutes of awakening — the cortisol awakening response (CAR) — then fall to a nadir by late evening. Measurement uses morning serum or serial saliva; the CAR is captured at wake-up, +15 min, and +30 min. Chronic HPA overactivity — elevated evening cortisol, a flattened diurnal slope, or a blunted CAR — drives skeletal-muscle catabolism via glucocorticoid receptor–mediated suppression of IGF-1 signalling and ubiquitin–proteasome activation, accelerating sarcopenic muscle-mass loss. Lower overall diurnal output associates with longevity: in the Leiden Longevity Study (Noordam 2012), offspring of nonagenarian siblings showed significantly lower diurnal salivary cortisol than age-matched controls, independent of health behaviours. A scoping review by Palmese et al. (2025) in European Geriatric Medicine found consistent associations between a steeper diurnal drop and faster gait speed, better chair-rise time, and lower frailty risk, but the authors classify the evidence as fragmented and insufficient to establish causation. The link with cognitive aging is also associational: in the Whitehall II and NSHD cohorts (Tsui 2020, Neurology), a higher morning-to-evening ratio at mid-life prospectively linked to better later cognitive scores, while blunted variation predicted worse performance.