HE435 Lecture Notes - Lecture 23: Elastin, Gas Exchange, Vascular Smooth Muscle
Document Summary
Successful aging: chronologic age and physiologic age not the same, due to complex interactions of genetics & environment. 9 hallmarks of aging: genomic instability, accumulation of genetic damage. Impaired pro homeostasis: ability to repair misfold polypeptides or remove them, accumulation of damaged components leads to aging/disease , 2 principle proteolytic systems, 1) autophagy-lysosomal system, 2) ubiquitin-proteasome system, both systems decline with aging, deregulated nutrient sensing. Insulin and igf-1 signaling pathway is preserved: brain needs glucose to function (evolutionary?) Issues to this nutrient sensing pathway = aging: accelerated aging, other interconnected systems, ampk, sirt, mtor, foxo, short term activation vs long term over-activation, mitochondrial dysfunction, efficacy of respiratory chain diminishes with aging. Increasing electron leakage and reducing atp generation: mitochondrial free radical theory of aging. Increased ros production causes further mitochondrial dysfunction: some ros is good, too much ros is problematic, trigger inflammatory response. Impact cell signaling and organ cross-talk: mitochondrial deficiencies affect apoptotic signalling, mitohormesis some negative stimuli increase repair.
