UCL（University College London）的科學家發(fā)現(xiàn),，缺少胰島素受體底物（IRS）-1的老鼠對衰老抵抗力更強。這為胰島素信號通路在哺乳動物衰老中的作用提供了新證據(jù),。
小組研究了通過基因改造后缺少IRS-1或-2的老鼠,。IRS通過胰島素激活，胰島素負責調(diào)節(jié)葡萄糖和脂肪代謝,。發(fā)表在FASEB上的結(jié)果顯示,，缺少IRS-1的老鼠壽命比同類長20％。在雌性老鼠中現(xiàn)象更明顯,，平均達到30％,。老鼠預期壽命一般為25月左右，而其中一個缺少IRS-1的老鼠壽命達到了38月－比同類長66％,。
除了壽命更長,，缺少IRS-1的老鼠在老年時也更健康，它們視力更好也更警惕,。而缺少IRS-2的老鼠壽命則有所減少,，且表現(xiàn)出肥胖和2型糖尿病。來自UCL衰老研究中心的Dominic Withers教授是文章主要作者,，他說：“缺少IRS-1使老鼠,，特別是雌性老鼠對衰老抵抗力更強，包括皮膚,、骨骼,、免疫和運動等方面。這表明IRS-1是進化中產(chǎn)生的調(diào)節(jié)哺乳動物壽命的通路，利用它可能找到延緩人類衰老的方法,。”
他還說：“我們并不完全清楚缺少IRS-1為何會延長壽命,。其中一種可能解釋是對胰島素的輕微耐受不會對身體造成影響，而且能增強壓力抵抗力,，防止損傷并激發(fā)身體延長壽命的反應,。”另一作者David Gems說：“胰島素通路單個基因的變異能延長壽命。而我們發(fā)現(xiàn)這還能使老鼠變得更健康,，延緩衰老疾病例如骨質(zhì)疏松等發(fā)生,。顯然研究人類的類似機制很困難，但我們的研究提供了很關鍵的基礎,。”
UCL小組還研究過果蠅,、線蟲等，并于2007年6月得到了510萬英鎊的經(jīng)費支持,。UCL衰老健康研究所將于2008年建成,，他們鼓勵其他學者和UCL進行該領域的合作。（教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news112279922.html
原始出處:
Published online before print October 10, 2007 as doi: 10.1096/fj.07-9261com.
Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice
Colin Selman, Steven Lingard, Agharul I. Choudhury, Rachel L. Batterham, Marc Claret, Melanie Clements, Faruk Ramadani, Klaus Okkenhaug, Eugene Schuster, Eric Blanc, Matthew D. Piper, Hind Al-Qassab, John R. Speakman, Danielle Carmignac, Iain C. A. Robinson, Janet M. Thornton, David Gems, Linda Partridge, and Dominic J. Withers
E-mail contact: [email protected].
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.
