Aging Cell | |
Celecoxib extends C. elegans lifespan via inhibition of insulin‐like signaling but not cyclooxygenase‐2 activity | |
Tsui-Ting Ching1  Wei-Chung Chiang3  Ching-Shih Chen2  | |
[1] Department of Internal Medicine, Division of Geriatric Medicine;Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA;Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA | |
关键词: 3′‐phosphoinositide‐dependent kinase‐1; Caenorhabditis elegans; celecoxib; cyclooxygenase‐2 inhibitor; insulin‐like signaling; longevity; nonsteroidal anti‐inflammatory drug; | |
DOI : 10.1111/j.1474-9726.2011.00688.x | |
来源: Wiley | |
【 摘 要 】
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.Summary
【 授权许可】
Unknown
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland
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