With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging.
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.
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA. pkapahi@buckinstitute.org
Pankaj
P
Kapahi
Di
D
Chen
Aric N
AN
Rogers
Subhash D
SD
Katewa
Patrick Wai-Lun
PW
Li
Emma L
EL
Thomas
Lutz
L
Kockel
D000375:Aging; D000818:Animals; D001343:Autophagy; D004721:Endoplasmic Reticulum / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D008136:Longevity; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases