An anti-aging drug today: from senescence-promoting genes to anti-aging pill.
Numerous mutations increase lifespan in diverse organisms from worms to mammals. Most genes that affect longevity encode components of the target of rapamycin (TOR) pathway, thus revealing potential targets for pharmacological intervention. I propose that one target, TOR itself, stands out, simply because its inhibitor (rapamycin) is a non-toxic, well-tolerated drug that is suitable for everyday oral administration. Preclinical and clinical data indicate that rapamycin is a promising drug for age-related diseases and seems to have anti-tumor, bone-sparing and calorie-restriction-mimicking 'side-effects'. I also discuss other potential anti-aging agents (calorie restriction, metformin, resveratrol and sirtuins) and their targets, interference with the TOR pathway and combination with antioxidants.
Blagosklonny
Mikhail V
MV
Oncotarget Inc., Albany, NY 12203, USA. blagosklonny@oncotarget.com
D000375:Aging / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D031204:Caloric Restriction; D018797:Cell Cycle Proteins / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects / Q000235:genetics; D008687:Metformin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects; D000077185:Resveratrol; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects; D020123:Sirolimus / Q000009:adverse effects / Q000494:pharmacology*; D037761:Sirtuins / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology
D000975:Antioxidants; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D029701:Saccharomyces cerevisiae Proteins; D013267:Stilbenes; D008687:Metformin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae; D037761:Sirtuins; D000077185:Resveratrol; D020123:Sirolimus