TY - JOUR TI - A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice AU - Petr, Michael A AU - Alfaras, Irene AU - Krawcyzk, Melissa AU - Bair, Woei-Nan AU - Mitchell, Sarah J AU - Morrell, Christopher H AU - Studenski, Stephanie A AU - Price, Nathan L AU - Fishbein, Kenneth W AU - Spencer, Richard G AU - Scheibye-Knudsen, Morten AU - Lakatta, Edward G AU - Ferrucci, Luigi AU - Aon, Miguel A AU - Bernier, Michel AU - de Cabo, Rafael A2 - Justice, Jamie A2 - Tyler, Jessica K VL - 10 PY - 2021 DA - 2021/04/20 SP - e62952 C1 - eLife 2021;10:e62952 DO - 10.7554/eLife.62952 UR - https://doi.org/10.7554/eLife.62952 AB - 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. KW - Aging KW - Metabolism KW - gait KW - physiology KW - Metabolomics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -