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The Antiaging Activity and Cerebral Protection of Rapamycin at Micro‐doses
Author(s) -
Qi Haiyan,
Su FengYun,
Wan Shan,
Chen Yongjie,
Cheng YanQiong,
Liu AiJun
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12338
Subject(s) - autophagy , pharmacology , neurotoxin , cell growth , neuron , stroke (engine) , neurotoxicity , medicine , chemistry , toxicity , apoptosis , biology , neuroscience , biochemistry , mechanical engineering , engineering
Summary Background and purpose The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC 1 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. Methods and results We demonstrated that rapamycin at micro‐doses (below the TORC 1 inhibiting concentration) exhibits a cell‐protective activity: (1) It protects cultured neurons against neurotoxin MPP + and H 2 O 2 . (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 ‐ SP s). Conclusion We propose that rapamycin at micro‐dose can be developed into an antiaging agent with a novel mechanism.

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