A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice
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
Affiliations
Michael A Petr
Center for Healthy Aging, ICMM, University of Copenhagen, Copenhagen, Denmark; Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
Irene Alfaras
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
Melissa Krawcyzk
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, United States
Woei-Nan Bair
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States; Department of Physical Therapy, University of Sciences, Philadelphia, United States
Sarah J Mitchell
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
Christopher H Morrell
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, United States
Stephanie A Studenski
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, United States
Nathan L Price
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States; Integrative Cell Signaling and Neurobiology of Metabolism Program, Yale University School of Medicine, New Haven, United States; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, United States; Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States; Department of Pathology, Yale University School of Medicine, New Haven, United States
Kenneth W Fishbein
Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States
Richard G Spencer
Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States
Morten Scheibye-Knudsen
Center for Healthy Aging, ICMM, University of Copenhagen, Copenhagen, Denmark
Edward G Lakatta
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, United States
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
Miguel A Aon
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States; Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, United States
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.
