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Aging Cell. 2011 Jun;10(3):506-19. doi: 10.1111/j.1474-9726.2011.00688.x. Epub 2011 Apr 7.

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

Author information

1
Department of Internal Medicine, Division of Geriatric Medicine, University of Michigan Medical School, Ann Arbor, 48109, USA.

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.

PMID:
21348927
PMCID:
PMC3094508
DOI:
10.1111/j.1474-9726.2011.00688.x
[Indexed for MEDLINE]
Free PMC Article

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