Rapamycin and the inhibition of the secretory phenotype.
Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Cell senescence is a complex process that can be triggered by multiple challenges. Recently it has been observed that the composition of the secretory phenotype or SASP depends on the insult that triggers cell senescence. Rapamycin, an inhibitor of mTOR that increases longevity in several species, inhibits cell senescence in vitro, while silencing the Nrf2 gene induces premature senescence. We have found that rapamycin activates the Nrf2 pathway to regulate cell cycle arrest, but not the production of SASP, which is regulated by a different pathway, probably involving the inhibition of MAPKAPK2.
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, United States.
Rong
R
Wang
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, United States.
Bharath
B
Sunchu
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, United States; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, United States. Electronic address: Viviana.perez@oregonstate.edu.
Viviana I
VI
Perez
D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D051267:NF-E2-Related Factor 2; D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
Cell cycle arrest; Cell senescence; Nrf2; Rapamycin; SASP