With TOR, Less is more: a key role for the conserved nutrient-sensing TOR pathway in Aging

Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Cell metabolism (Impact Factor: 17.57). 06/2010; 11(6):453-65. DOI: 10.1016/j.cmet.2010.05.001
Source: PubMed


Target of rapamycin (TOR) is an evolutionarily conserved nutrient-sensing protein kinase that regulates growth and metabolism in all eukaryotic cells. Studies in flies, worms, yeast, and mice support the notion that the TOR signaling network modulates aging. TOR is also emerging as a robust mediator of the protective effects of various forms of dietary restriction (DR), which can extend life span and slow the onset of certain age-related diseases across species. Here we discuss how modulating TOR signaling slows aging through downstream processes including mRNA translation, autophagy, endoplasmic reticulum (ER) stress signaling, stress responses, and metabolism. Identifying the mechanisms by which the TOR signaling network works as a pacemaker of aging is a major challenge and may help identify potential drug targets for age-related diseases, thereby facilitating healthful life span extension in humans.

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Available from: Subhash D Katewa, Dec 17, 2013
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    • "A reduction in protein synthetic burden may preserve proteostasis by limiting the accumulation of misfolded and/or damaged proteins, possibly by increasing translational fidelity, chaperone capacity, and/or proteolytic capacity (Hipkiss, 2007; Kapahi et al., 2010; Conn & Qian, 2013; Sherman & Qian, 2013). In addition, when global protein synthesis is inhibited, differential translational upregulation of mRNAs encoding proteins involved in somatic maintenance and stress responses has been reported (Yamasaki & Anderson, 2008; Kapahi et al., 2010). Conversely, a primary reduction in damage to proteins, induction of chaperone synthesis, or a primary increase in proteolytic capacity (i.e., improved editing) could improve proteostasis independently of the absolute rate of protein synthesis in tissues. "
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