Pathophysiology
Clinical meaning
Frailty is a clinically recognizable state of increased vulnerability resulting from aging-associated decline in physiologic reserve and function across multiple organ systems, such that the ability to cope with acute or everyday stressors is compromised. The frailty phenotype (Fried criteria) identifies 5 measurable components: unintentional weight loss (>= 10 lbs or >= 5% body weight in past year), exhaustion (self-reported), weakness (grip strength in lowest 20% for sex and BMI), slow walking speed (<0.8 m/s over 4 meters), and low physical activity. Pre-frail = 1-2 criteria present; Frail = >= 3 criteria present. Pathophysiology involves dysregulation of multiple interconnected systems: (1) Chronic inflammation ('inflammaging') - elevated IL-6, TNF-alpha, CRP drive sarcopenia, anemia, and immune dysfunction; (2) Neuroendocrine dysregulation - decreased IGF-1, DHEA-S, testosterone, and growth hormone reduce anabolic drive while elevated cortisol promotes catabolism; (3) Sarcopenia - progressive loss of skeletal muscle mass and strength (driven by inflammation, hormonal changes, decreased physical activity, inadequate protein intake, and mitochondrial dysfunction); (4) Immune senescence - impaired T-cell function, reduced vaccine responses, increased susceptibility to infection; (5) Metabolic dysregulation - insulin resistance, dyslipidemia,...