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These effects were preceded by induction of oxidative stress (increased levels of reactive oxygen species and DNA damage) and impairment of cells' GSH redox state. Curcumin also induced nuclear factor\u2010erythroid\u20102\u2010related factor 2 accumulation in the nuclei. The use of the antioxidant <jats:italic>N<\/jats:italic>\u2010acetyl cysteine prevented the induction of HO\u20101 by curcumin. Pharmacological inhibition of phosphatidylinositol 3\u2010kinase, but not other kinases, significantly prevented curcumin\u2010induced HO\u20101 levels, which was corroborated by the induction of phospho\u2010Akt levels by curcumin. Late passage senescent cells already had higher HO\u20101 levels, and further induction of HO\u20101 by curcumin was considerably impaired. The induction of stress responses by curcumin in human cells led to protective hormetic effects to further oxidant challenge.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Curcumin induces cellular stress responses in normal human skin fibroblasts through phosphatidylinositol 3\u2010kinase\/Akt pathway and redox signaling, supporting the view that curcumin\u2010induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti\u2010aging intervention.<\/jats:p>","DOI":"10.1002\/mnfr.201000221","type":"journal-article","created":{"date-parts":[[2010,10,11]],"date-time":"2010-10-11T10:51:47Z","timestamp":1286794307000},"page":"430-442","source":"Crossref","is-referenced-by-count":120,"title":["Curcumin induces heme oxygenase\u20101 in normal human skin fibroblasts through redox signaling: Relevance for anti\u2010aging intervention"],"prefix":"10.1002","volume":"55","author":[{"given":"Cristovao F.","family":"Lima","sequence":"first","affiliation":[]},{"given":"Cristina","family":"Pereira\u2010Wilson","sequence":"additional","affiliation":[]},{"given":"Suresh I. 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