Cardiolipin induces premature senescence in normal human fibroblasts.
Lipids seem to have various roles in cellular senescence. We found that cardiolipin very sensitively inhibits growth of normal human fibroblasts, whereas other phospholipids do not at 100 times higher concentrations. Growth arrested cells showed morphology similar to those of normally senesced cells and strongly induced senescence-associated beta-galactosidase. Senescence markers such as the p21(waf1/sdi-1), fibronectin, and collagenase-I genes were significantly upregulated by cardiolipin. In addition, caldiolipin significantly increased in normally senesced human fibroblasts leaving other phospholipids unaltered. These results suggest that accumulation of cardiolipin is one of the causes for replicative senescence.
Arivazhagan
Palaniyappan
P
Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Yokohama 244-0813, Japan.
Mizutani
Emi
E
Fujii
Michihiko
M
Ayusawa
Dai
D
D002308:Cardiolipins / Q000378:metabolism* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans
D002308:Cardiolipins