title: The antiaging activity and cerebral protection of rapamycin at micro-doses.
abstract: OBJECTIVE
  The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC1 inhibition that inhibits cell proliferation and increases autophagy. However, rapamycin also exhibits a number of harmful adverse effects. Whether rapamycin can be developed into an antiaging agent remains unclear.
  
  
  RESULTS
  We demonstrated that rapamycin at micro-doses (below the TORC1 inhibiting concentration) exhibits a cell-protective activity: (1) It protects cultured neurons against neurotoxin MPP(+) and H2O2. (2) It increases survival time of neuron in culture. (3) It maintains the nonproliferative state of cultured senescent human fibroblasts and prevents cell death induced by telomere dysfunction. (4) In animal models, it decreased the cerebral infarct sizes induced by acute ischemia and dramatically extended the life span of stroke prone spontaneously hypertensive rats (SHR-SPs).
  
  
  CONCLUSIONS
  We propose that rapamycin at micro-dose can be developed into an antiaging agent with a novel mechanism.
authors.affiliation: Springcell Corporation, Dayton, NJ, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qi
authors.forename: Feng-Yun
authors.initials: FY
authors.lastname: Su
authors.forename: Shan
authors.initials: S
authors.lastname: Wan
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Chen
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Cheng
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D002540:Cerebral Cortex / Q000187:drug effects*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D016559:Tacrolimus / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D006861:Hydrogen Peroxide; D001616:beta-Galactosidase; D020123:Sirolimus; D016559:Tacrolimus
keywords: Antiaging; Ischemic infarction; Life span; Rapamycin; Senescence