Molecular mechanism of extrinsic factors affecting antiagingof stem cells

Scientific evidence suggests that stem cells possessthe anti-aging ability to self-renew and maintaindifferentiation potentials, and quiescent state. Theobjective of this review is to discuss the microenvironmentwhere stem cells reside in vivo , thesecreted factors to which stem cells are exposed, thehypoxic environment, and intracellular factors includinggenome stability, mitochondria integrity, epigeneticregulators, calorie restrictions, nutrients, and vitaminD. Secreted tumor growth factor-β and fibroblastgrowth factor-2 are reported to play a role in stem cellquiescence. Extracellular matrices may interact withcaveolin-1, the lipid raft on cell membrane to regulatequiescence. N-cadherin, the adhesive protein on nichecells provides support for stem cells. The hypoxicmicro-environment turns on hypoxia-inducible factor-1to prevent mesenchymal stem cells aging throughp16 and p21 down-regulation. Mitochondria expressglucosephosphate isomerase to undergo glycolysisand prevent cellular aging. Epigenetic regulators suchas p300, protein inhibitors of activated Stats and H19help maintain stem cell quiescence. In addition, calorierestriction may lead to secretion of paracrines cyclicADP-ribose by intestinal niche cells, which help maintainintestinal stem cells. In conclusion, it is crucial tounderstand the anti-aging phenomena of stem cells atthe molecular level so that the key to solving the agingmystery may be unlocked.