Clinical meaning
Aging produces predictable physiological changes across organ systems that alter disease presentation, drug metabolism, and functional capacity. Cardiovascular changes include decreased arterial compliance (increased afterload), reduced maximal heart rate responsiveness, and diastolic dysfunction from myocardial fibrosis, making older adults vulnerable to heart failure with preserved ejection fraction. Renal function declines approximately 1 mL/min/year after age 40 due to progressive nephrosclerosis, reducing drug clearance and increasing susceptibility to nephrotoxicity — critically, serum creatinine may remain normal despite significant GFR reduction because of decreased muscle mass. Hepatic blood flow decreases by 30-40%, reducing first-pass metabolism of drugs such as propranolol and morphine. The CNS undergoes neuronal loss, decreased neurotransmitter synthesis (particularly acetylcholine and dopamine), and blood-brain barrier changes that increase sensitivity to CNS-active medications. Sarcopenia (age-related muscle loss of 1-2% per year after age 50) reduces lean body mass, altering volume of distribution for hydrophilic drugs while increasing body fat percentage expands distribution for lipophilic drugs (prolonging elimination half-life of benzodiazepines and fat-soluble agents). The Comprehensive Geriatric Assessment (CGA) systematically evaluates multiple domains — functional status (ADLs/IADLs), cognition, mood, nutrition, mobility, polypharmacy,...