Institute of Biological and Environmental Sciences, School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom.
PLoS One. 2011 Jan 25;6(1):e16144. doi: 10.1371/journal.pone.0016144.
We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice. However, no effect on lifespan was observed in male Irs1 null mice. We suggested at the time that the lack of any effect in males might have been due to a sample size issue. While such lifespan studies are essential to our understanding of the aging process, they are generally based on survival curves derived from single experiments, primarily due to time and economic constraints. Consequently, the robustness of such findings as a basis for further investigation has been questioned. We have therefore measured lifespan in a second, separate cohort of Irs1 null female mice, and show that, consistent with our previous finding, global deletion of Irs1 significantly extends lifespan in female mice. In addition, an augmented and completed study demonstrates lifespan extension in male Irs1 null mice. Therefore, we show that reduced IRS1-dependent signalling is a robust mechanism through which mammalian lifespan can be modulated.
我们之前报道过，胰岛素受体底物蛋白 1（Irs1）的全局缺失可延长雌性小鼠的寿命并提高其对多种与年龄相关的病理的抗性。然而，在雄性 Irs1 缺失小鼠中未观察到对寿命的影响。当时我们推测，男性中没有任何影响可能是由于样本量问题。虽然这些寿命研究对于我们理解衰老过程至关重要，但它们通常基于单个实验得出的生存曲线，主要是由于时间和经济限制。因此，作为进一步研究基础的这些发现的稳健性受到了质疑。因此，我们在第二个独立的 Irs1 缺失雌性小鼠队列中测量了寿命，并表明与我们之前的发现一致，Irs1 的全局缺失可显著延长雌性小鼠的寿命。此外，一项增强和完成的研究表明，雄性 Irs1 缺失小鼠的寿命也得到了延长。因此，我们表明，减少 IRS1 依赖性信号传递是一种可以调节哺乳动物寿命的稳健机制。
