Open AccessCelecoxib extends C. elegans lifespan via inhibition of insulin‐like signaling but not cyclooxygenase‐2 activity
Author(s) -
Ching TsuiTing,
Chiang WeiChung,
Chen ChingShih,
Hsu AoLin
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00688.x
Subject(s) - celecoxib , cyclooxygenase , proteotoxicity , biology , pharmacology , caenorhabditis elegans , inflammation , insulin , inhibitory postsynaptic potential , kinase , neuroscience , endocrinology , microbiology and biotechnology , enzyme , gene , biochemistry , protein aggregation , immunology
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.