Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans).
Although it has been known since 1917 that calorie restriction (CR) decelerates aging, the topic remains highly controversial. What might be the reason? Here I discuss that the anti-aging effect of CR rules out accumulation of DNA damage and failure of maintenance as a cause of aging. Instead, it suggests that aging is driven in part by the nutrient-sensing TOR (target of rapamycin) network. CR deactivates the TOR pathway, thus slowing aging and delaying diseases of aging. Humans are not an exception and CR must increase both maximal and healthy lifespan in humans to the same degree as it does in other mammals. Unlike mice, however, humans benefit from medical care, which prolongs lifespan despite accelerated aging in non-restricted individuals. Therefore in humans the effect of CR may be somewhat blunted. Still how much does CR extend human lifespan? And could this extension be surpassed by gerosuppressants such as rapamycin?
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA. Blagosklonny@oncotarget.com
Mikhail V
MV
Blagosklonny
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging; D031204:Caloric Restriction; D016922:Cellular Senescence; D006801:Humans; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008136:Longevity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D037761:Sirtuins