title: Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity.
abstract: One goal of aging research is to develop interventions that combat age-related illnesses and slow aging. Although numerous mutations have been shown to achieve this in various model organisms, only a handful of chemicals have been identified to slow aging. Here, we report that celecoxib, a nonsteroidal anti-inflammatory drug widely used to treat pain and inflammation, extends Caenorhabditis elegans lifespan and delays the age-associated physiological changes, such as motor activity decline. Celecoxib also delays the progression of age-related proteotoxicity as well as tumor growth in C. elegans. Celecoxib was originally developed as a potent cyclooxygenase-2 (COX-2) inhibitor. However, the result from a structural-activity analysis demonstrated that the antiaging effect of celecoxib might be independent of its COX-2 inhibitory activity, as analogs of celecoxib that lack COX-2 inhibitory activity produce a similar effect on lifespan. Furthermore, we found that celecoxib acts directly on 3'-phosphoinositide-dependent kinase-1, a component of the insulin/IGF-1 signaling cascade to increase lifespan.
authors.affiliation: Department of Internal Medicine, Division of Geriatric Medicine, University of Michigan Medical School, Ann Arbor, 48109, USA.
authors.forename: Tsui-Ting
authors.initials: TT
authors.lastname: Ching
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Chiang
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.forename: Ao-Lin
authors.initials: AL
authors.lastname: Hsu
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D051858:Forkhead Transcription Factors; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008136:Longevity; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013449:Sulfonamides; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D029742:Caenorhabditis elegans Proteins; D052246:Cyclooxygenase 2 Inhibitors; D051858:Forkhead Transcription Factors; D007328:Insulin; D011720:Pyrazoles; D013449:Sulfonamides; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D051546:Cyclooxygenase 2; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000068579:Celecoxib