Maf1â€dependent transcriptional regulation of tRNAs prevents genomic instability and is associated with extended lifespan – Shetty – – Aging Cell – Wiley Online Library
“Fundamental cellular mechanisms such as nutrient sensing, DNA damage response pathways, and cell cycle regulation influence the aging process. Studies have shown that the nutrient sensory kinase, mTOR (TOR in yeast), regulates lifespan in response to nutrient availability. The mTOR kinase forms two distinct protein complexes: TORC1 and TORC2. TORC1, which is inhibited by rapamycin, regulates cell growth, proliferation, and metabolism. It is well established that TORC1 promotes protein translation via phosphorylation of ribosomal protein S6 kinase and the eIF4Eâ€binding protein (BP; Zoncu, Efeyan, & Sabatini, 2011). The TORC2 branch is less studied; however, TORC2 also plays important roles in metabolism, cell survival, and proliferation (Zoncu et al., 2011). Although the involvement of the TORC1 pathway in lifespan regulation is conserved among many species (i.e., TORC1 inhibition extends lifespan), it is still unclear how this pathway affects multiple downstream stress and damage response mechanisms.”