2/18/2023 0 Comments Tor miller 2017![]() mTOR responds to amino acids, a pathway modulated by proteins such as sestrins. These transcription factors also control autophagy, a cellular process that clears proteins and dysfunctional organelles, and reduces proteotoxic and oxidative stress while maintaining a pool of amino acids for protein synthesis. mTOR acts upstream of several transcription factors, such as TFEB, FOXO, FOXA, and Nrf, that are essential for lifespan-extending strategies such as dietary restriction. A controlling hub at the center of nutrient sensing and signaling is the mechanistic target of rapamycin (mTOR) that governs cellular growth, protein synthesis, and degradation. The fundamental mechanisms from signaling cascades to protein complexes are conserved across phyla. The most studied and best understood longevity pathways govern metabolism according to available nutrient levels. ![]() We suggest that conserved molecular pathways have the strongest potential for the development of new avenues for treatment of age-related diseases. Furthermore, we review research on the regulation of metabolism conducted in multiple aging models, including Caenorhabditis elegans, Drosophila and mouse, and human iPSCs. In this review, we discuss the current progress in understanding the contribution of mTOR-regulating factors to autophagy and longevity. ![]() This key metabolic pathway strongly depends on nucleocytoplasmic compartmentalization, a cellular phenomenon gradually lost during aging. In response to environmental cues, this recently discovered lysosomal nutrient-sensing complex regulates autophagy transcriptionally through conserved factors, such as the transcription factors TFEB and FOXO, associated with lifespan extension. ![]() The nutrient-sensing pathway is regulated at the lysosomal membrane by a number of proteins for which deficiency triggers widespread aging phenotypes in tested animal models. The mTOR pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. Cellular metabolism is regulated by the mTOR kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging.
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