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PMID: 16441841 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Review

Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for pharmacological manipulation of lifespan.

Aging cell ·Vol. 5 ·No. 1 ·2006-02-00 ·Pages 31-7

Gami MS, Wolkow CA

Abstract

Much excitement has arisen from the observation that decrements in insulin-like signaling can dramatically extend lifespan in the nematode, Caenorhabditis elegans, and fruitfly, Drosophila melanogaster. In addition, there are tantalizing hints that the IGF-I pathway in mice may have similar effects. In addition to dramatic effects on lifespan, invertebrate insulin-like signaling also promotes changes in stress resistance, metabolism and development. Which, if any, of the various phenotypes of insulin pathway mutants are relevant to longevity? What are the genes that function in collaboration with insulin to prolong lifespan? These questions are at the heart of current research in C. elegans longevity. Two main theories exist as to the mechanism behind insulin's effects on invertebrate longevity. One theory is that insulin programs metabolic parameters that prolong or reduce lifespan. The other theory is that insulin determines the cell's ability to endure oxidative stress from respiration, thereby determining the rate of aging. However, these mechanisms are not mutually exclusive and several studies seem to support a role for both. Here, we review recently published reports investigating the mechanisms behind insulin's dramatic effect on longevity. We also spotlight several C. elegans genes that are now known to interact with insulin signaling to determine lifespan. These insights into pathways affecting invertebrate lifespan may provide a basis for developing strategies for pharmacological manipulation of human lifespan.

MeSH Terms
Animals Caenorhabditis elegans/physiology Caenorhabditis elegans Proteins/metabolism Drug Evaluation, Preclinical Humans Insulin/metabolism Longevity/drug effects Receptor, Insulin/metabolism Signal Transduction
Chemicals
Caenorhabditis elegans Proteins Insulin DAF-2 protein, C elegans Receptor, Insulin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gami Minaxi S
Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Wolkow Catherine A
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Article Info
Journal
Aging cell
Abbr.
Aging Cell
ISSN
1474-9718
DOI
10.1111/j.1474-9726.2006.00188.x
Published
2006-02-00
Pages
31-7
Language
English
Region
England
NLM ID
101130839
PMCID
PMC1413578
Subset
IM
Grants
Intramural NIH HHS · NIH0011061953 · United States
Intramural NIH HHS · Z01 AG000320-06 · United States
External Links
PubMed source DOI: 10.1111/j.1474-9726.2006.00188.x PMC Full Text View journal details
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