Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA.
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Baltimore, MD 21224, USA.
Cell Metab. 2021 Nov 2;33(11):2189-2200.e3. doi: 10.1016/j.cmet.2021.08.013. Epub 2021 Sep 10.
Aging leads to profound changes in glucose homeostasis, weight, and adiposity, which are considered good predictors of health and survival in humans. Direct evidence that these age-associated metabolic alterations are recapitulated in animal models is lacking, impeding progress to develop and test interventions that delay the onset of metabolic dysfunction and promote healthy aging and longevity. We compared longitudinal trajectories, rates of change, and mortality risks of fasting blood glucose, body weight, and fat mass in mice, nonhuman primates, and humans throughout their lifespans and found similar trajectories of body weight and fat in the three species. In contrast, fasting blood glucose decreased late in life in mice but increased over the lifespan of nonhuman primates and humans. Higher glucose was associated with lower mortality in mice but higher mortality in nonhuman primates and humans, providing a cautionary tale for translating age-associated metabolic changes from mice to humans.
衰老会导致葡萄糖稳态、体重和肥胖发生深刻变化,这些变化被认为是人类健康和生存的良好预测指标。缺乏直接证据表明这些与年龄相关的代谢变化在动物模型中得到了重现,这阻碍了开发和测试干预措施的进展,这些干预措施可以延缓代谢功能障碍的发生,促进健康衰老和长寿。我们比较了小鼠、非人灵长类动物和人类在整个生命周期中空腹血糖、体重和脂肪量的纵向轨迹、变化率和死亡率风险,发现这三种物种的体重和脂肪轨迹相似。相比之下,小鼠在生命后期空腹血糖降低,但在非人类灵长类动物和人类的生命周期中增加。血糖升高与小鼠的低死亡率相关,但与非人类灵长类动物和人类的高死亡率相关,这为将与年龄相关的代谢变化从小鼠转化为人类提供了一个警示故事。