A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice.
A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice.
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DOI：
10.7554/elife.62952
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发表时间：
2021-04-20
期刊：
影响因子：
7.7
通讯作者：
de Cabo R
中科院分区：
文献类型：
--
作者：
Petr MA;Alfaras I;Krawcyzk M;Bair WN;Mitchell SJ;Morrell CH;Studenski SA;Price NL;Fishbein KW;Spencer RG;Scheibye-Knudsen M;Lakatta EG;Ferrucci L;Aon MA;Bernier M;de Cabo R
衰老与不同的表型、生理和功能变化相关，导致疾病和死亡。衰老相关特征的进展在个体之间差异很大，受环境，生活方式和遗传学的影响。在这项研究中，我们在雄性C57 BL/6 N小鼠的整个生命周期中进行了横截面的生理和功能测试。同时，还进行了血清、脑、肝、心脏和骨骼肌中的代谢组学分析，以鉴定与虚弱和年龄依赖性功能下降相关的特征。我们的研究结果表明，随着年龄和虚弱程度的增加，步态速度的下降与体力活动的能量消耗急剧增加和工作能力下降有关。衰老和功能下降促使器官重新连接其代谢和底物选择，并朝向氧化还原相关途径，主要是在肝脏和心脏中。总的来说，这些数据提供了一个框架，以进一步了解和表征个体生物体和器官水平的衰老过程。
Aging is associated with distinct phenotypical, physiological, and functional changes, leading to disease and death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, and genetics. In this study, we conducted physiologic and functional tests cross-sectionally throughout the entire lifespan of male C57BL/6N mice. In parallel, metabolomics analyses in serum, brain, liver, heart, and skeletal muscle were also performed to identify signatures associated with frailty and age-dependent functional decline. Our findings indicate that declines in gait speed as a function of age and frailty are associated with a dramatic increase in the energetic cost of physical activity and decreases in working capacity. Aging and functional decline prompt organs to rewire their metabolism and substrate selection and toward redox-related pathways, mainly in liver and heart. Collectively, the data provide a framework to further understand and characterize processes of aging at the individual organism and organ levels.