title: 2,5-Dimethyl-Celecoxib Extends Drosophila Life Span via a Mechanism That Requires Insulin and Target of Rapamycin Signaling.
abstract: The search for antiaging drugs is a key component of gerontology research. A few drugs with positive effects on life span in model organisms have been found. Here, we report that 2,5-dimethyl-celecoxib, a derivative of the anti-inflammatory drug celecoxib, can extend Drosophila life span and delay aging by a mechanism involving insulin signaling and target of rapamycin signaling. Importantly, its positive effects were apparent when the treatment window was restricted to the beginning of life or the later half. 2,5-Dimethyl-celecoxib-induced longevity was also associated with improvements in physical activity, intestinal integrity, and increased autophagy. In addition, 2,5-dimethyl-celecoxib exhibited protective effects against several kinds of stress such as starvation and heat. The generally positive effects of 2,5-dimethyl-celecoxib on both health and life span, combined with its mode of action via evolutionarily conserved signaling pathways, indicate that it has the potential to become an effective antiaging drug.
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lian
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Fan
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Chaochun
authors.initials: C
authors.lastname: Song
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Uma
authors.initials: U
authors.lastname: Gaur
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Mao
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Deying
authors.initials: D
authors.lastname: Yang
authors.affiliation: School of Biological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Matthew D W
authors.initials: MDW
authors.lastname: Piper
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D015870:Gene Expression; D007328:Insulin / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects*; D010641:Phenotype; D011720:Pyrazoles / Q000494:pharmacology*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C506698:2,5-dimethylcelecoxib; D029721:Drosophila Proteins; D007328:Insulin; D011720:Pyrazoles; D013449:Sulfonamides; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases
keywords: 2,5-Dimethyl-celecoxib; Drosophila; Life span; Mechanism