Normal Aging and Age-Related Physiology
Normal aging versus disease
Aging changes are predictable, gradual, and usually asymptomatic; disease is not. Key physiologic shifts include declining renal blood flow and GFR (roughly 8 mL/min/1.73 m² per decade after age 40), reduced hepatic phase I metabolism, decreased total body water with increased fat, lower lean mass, arterial stiffening with rising systolic and widened pulse pressure, blunted baroreflex and beta-adrenergic responsiveness, reduced maximal heart rate, decreased vital capacity and cough strength, immunosenescence, reduced thirst and thermoregulation, presbyopia and high-frequency hearing loss, slowed nerve conduction, and altered sleep architecture.
These changes alter drug handling: water-soluble drugs have a smaller volume of distribution (higher initial concentration), lipophilic drugs have a larger volume and longer half-life, and renally cleared drugs accumulate. A 'normal' creatinine can mask substantial CKD because sarcopenia lowers creatinine production.
Traps: labeling systolic hypertension, anemia, weight loss, incontinence, or cognitive slowing as 'normal aging.' None are. Also do not assume a creatinine of 1.0 mg/dL means normal GFR in a frail 85-year-old woman.
Worked example: an 80-year-old woman, 50 kg, creatinine 1.0 mg/dL. Cockcroft-Gault estimates creatinine clearance near 30 mL/min. Before ordering a renally cleared antibiotic or DOAC, calculate CrCl and adjust dose; avoid nephrotoxins and review hydration.
Rule of thumb: if a finding causes symptoms, loss of function, or progresses rapidly, it is disease until proven otherwise-not aging.