Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity

摘要: Understanding mechanisms of aging and determinants life span will help to reduce age-related morbidity facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence medical environmental factors, but maximal remains unchanged. Extension is currently possible in animal models with measures such genetic manipulations caloric restriction (CR). CR appears prolong by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which positively implicated cellular stress response mechanisms, highly regulated process controlled complex network intracellular signaling pathways. By sensing nutrient energy status, functional state mitochondria, concentration produced longevity regulates across co-ordinating information flow along its convergent, divergent multiply branched pathways, including vitagenes are genes involved preserving homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, thioredoxin sirtuin protein systems. Dietary antioxidants, carnosine, carnitines or polyphenols, have recently been demonstrated be neuroprotective through activation hormetic vitagenes. The dose-response, challenges long-standing beliefs about nature dose-response lowdose zone, having potential affect significantly design pre-clinical studies clinical trials well strategies optimal patient dosing treatment numerous diseases. Given broad cytoprotective properties there now strong interest discovering developing pharmacological agents capable inducing responses. In this review we discuss most current up date understanding restriction, restriction-mimetics compounds activating can enhance defensive systems bioenergetic resistance consequent impact on processes.