Researchers: Michael A Petr, Irene Alfaras, Melissa Krawcyzk, Woei-Nan Bair, Sarah J Mitchell, Christopher H Morrell, Stephanie A Studenski, Nathan L Price, Kenneth W Fishbein, Richard G Spencer, Morten Scheibye-Knudsen, Edward G Lakatta, Luigi Ferrucci, Miguel A Aon, Michel Bernier, Rafael de Cabo
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.