DOI: 10.1126/science.1142179. Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis

Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis

10.1126/science.1142179

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Reduced insulin-like signaling extends the life span of Caenorhabditis elegans and Drosophila . Here, we show that, in mice, less insulin receptor substrate–2 (Irs2) signaling throughout the body or just in the brain extended life span up to 18%. At 22 months of age, brain-specific Irs2 knockout mice were overweight, hyperinsulinemic, and glucose intolerant; however, compared with control mice, they were more active and displayed greater glucose oxidation, and during meals they displayed stable superoxide dismutase–2 concentrations in the hypothalamus. Thus, less Irs2 signaling in aging brains can promote healthy metabolism, attenuate meal-induced oxidative stress, and extend the life span of overweight and insulin-resistant mice.

Bibliography

Taguchi, A., Wartschow, L. M., & White, M. F. (2007). Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis. Science, 317(5836), 369â372.

Authors 3

Akiko Taguchi (first)
Lynn M. Wartschow (additional)
Morris F. White (additional)

References 24 Referenced 435

10.1146/annurev.ento.50.071803.130409
10.1111/j.1532-5415.2005.53490.x
10.1016/j.cell.2005.02.002
D. A. Sinclair, L. Guarente, Sci. Am.294, 48 (2006). / Sci. Am. (2006)
10.1073/pnas.0600161103
10.1126/science.1092952
10.1126/science.1057991
10.1038/nature02549
10.1038/36116
D. J. Withers et al., Nat. Genet.23, 32 (1999). / Nat. Genet. (1999)
D. W. Hosmer Jr. S. Lemeshow Applied Survival Analysis (Wiley New York 1999).
10.1016/j.cmet.2005.11.013
10.1172/JCI22217
10.1038/534
10.1126/science.290.5489.147
10.1038/35030105
10.1172/JCI24445
10.1523/JNEUROSCI.23-18-07084.2003
10.1152/physiolgenomics.00239.2005
10.1210/jc.2004-0390
10.1007/s10522-006-9065-3
10.1046/j.1474-9728.2002.00006.x
10.1016/S0531-5565(02)00153-5
We thank R. Leshan K. Martin C. Aubin N. Fujii and V. Petkovana for technical assistance and C. Lee J. Elmquist M. Anderson and H. Feldman for helpful advice. This work was supported by NIH (grants DK55326 and DK38712 to M.F.W.) the Japan Society for the Promotion of Science (A.T.) and the Yamada Science Foundation (A.T.). M.F.W. is an investigator at the Howard Hughes Medical Institute.

Dates

Type	When
Created	18 years, 1 month ago (July 19, 2007, 4:53 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 4:56 a.m.)
Indexed	4 weeks, 1 day ago (Aug. 7, 2025, 4:58 p.m.)
Issued	18 years, 1 month ago (July 20, 2007)
Published	18 years, 1 month ago (July 20, 2007)
Published Print	18 years, 1 month ago (July 20, 2007)

Funders 0

None

BibTeX

@article{Taguchi_2007, title={Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis}, volume={317}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1142179}, DOI={10.1126/science.1142179}, number={5836}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Taguchi, Akiko and Wartschow, Lynn M. and White, Morris F.}, year={2007}, month=jul, pages={369–372} }

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