Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice
Selman, C. and Lingard, S.J. and Choudhury, A.I. and Batterham, R.L. and Claret, M. and Clements, M. and Ramadani, F. and Okkenhaug, K. and Schuster, E. and Blanc, E. and Piper, M.D. and Al-Qassab, H. and Speakman, J.R. and Carmignac, D. and Robinson, I.C.A. and Thornton, Janet M. and Gems, D. and Partridge, L. and Withers, D.J. (2008) Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB Journal 22 , pp. 807-818. ISSN 0892-6638.
Recent evidence suggests that alterations in insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) can increase mammalian life span. For example, in several mouse mutants, impairment of the growth hormone (GH)/IGF1 axis increases life span and also insulin sensitivity. However, the intracellular signaling route to altered mammalian aging remains unclear. We therefore measured the life span of mice lacking either insulin receptor substrate (IRS) 1 or 2, the major intracellular effectors of the IIS receptors. Our provisional results indicate that female Irs1–/– mice are long-lived. Furthermore, they displayed resistance to a range of age-sensitive markers of aging including skin, bone, immune, and motor dysfunction. These improvements in health were seen despite mild, lifelong insulin resistance. Thus, enhanced insulin sensitivity is not a prerequisite for IIS mutant longevity. Irs1–/– female mice also displayed normal anterior pituitary function, distinguishing them from long-lived somatotrophic axis mutants. In contrast, Irs2–/– mice were short-lived, whereas Irs1+/– and Irs2+/– mice of both sexes showed normal life spans. Our results therefore suggest that IRS1 signaling is an evolutionarily conserved pathway regulating mammalian life span and may be a point of intervention for therapies with the potential to delay age-related processes.—Selman, C., Lingard, S., Choudhury, A. I., Batterham, A. L., Claret, M., Clements, M., Ramadani, F., Okkenhaug, K., Schuster, E., Blanc, E., Piper, M. D., Al-Qassab, H., Speakman, J. R., Carmignac, D., Robinson, I. C. A., Thornton, J. M., Gems, D., Partridge, L., Withers, D. J. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice.
|Keyword(s) / Subject(s):||aging, longevity, insulin signaling|
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Date Deposited:||04 Aug 2010 14:09|
|Last Modified:||17 Apr 2013 12:17|
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