摘要：During the last decade it was established that conservative growth hormone/ insulin-like growth factor-1 (IGF-1) and target of rapamycin (TOR) signaling pathways plays a key role in the control of aging and age-associated pathology in yeast, worms, insects and mammals [1-3]. mTORC1 (mammalian target of rapamycin complex 1) is activated by insulin and related growth factors through phosphatidylinositol-3-OH kinase and AKT kinase signaling and repressed by AMP-activated protein kinase, a key sensor of cellular energy status [1]. mTORC1 involved into promotion messenger RNA translation and protein synthesis through ribosomal protein S6 kinases (S6Ks) and 4E-BP protein. mTORC1 also stimulates lipid biosynthesis, inhibits autophagy, and through hypoxic response transcription factor HIF-1¦Á regulates mitochondrial function and glucose metabolism. The lifespan of S6K1 deficient female mice increased by 19% without effect on tumor development [see 1]. These data suggest that S6K1 plays a relevant role in lifespan regulation downstream of TORC1. Lamming et al. [4] have shown that decreased mTORC1 signaling is sufficient for lifespan prolongation independently from changes in glucose homeostasis. Rapamycin suppresses mTORC1 and indirectly mTORC2 that leads to metabolic lesions like glucose intolerance and abnormal lipid profile [1]. Treatment with rapamycin or its more soluble form rapatar increased the mean lifespan in various strain of mice [1-3,5-7]. It is worthy to note that the regulation of growth hormone and IGF-1, oxidative stress, DNA damage, and metabolic pathways by calorie restriction could simultaneously leads to its anti-aging and anti-tumor activities as well as to reduction of the number of senescent cells in some tissues [1,3].
