Celecoxib extends C. elegans lifespan via inhibition of insulin‐like signaling but not cyclooxygenase‐2 activity

• Published in: Aging cell 2011-06, Vol.10 (3), p.506-519
• Main Authors: Ching, Tsui‐Ting, Chiang, Wei‐Chung, Chen, Ching‐Shih, Hsu, Ao‐Lin
• Format: Article
• Language: English
• Subjects: 3-Phosphoinositide-Dependent Protein Kinases; 3′‐phosphoinositide‐dependent kinase‐1; Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans Proteins - metabolism; Celecoxib; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; cyclooxygenase‐2 inhibitor; Forkhead Transcription Factors; Genes; Insulin - metabolism; Insulin-Like Growth Factor I - antagonists & inhibitors; Insulin-Like Growth Factor I - metabolism; insulin‐like signaling; Longevity; Nematodes; nonsteroidal anti‐inflammatory drug; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Pyrazoles; Signal Transduction; Structure-Activity Relationship; Sulfonamides; Transcription Factors - metabolism
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/j.1474-9726.2011.00688.x

Summary 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.