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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

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere62952
JournaleLife
Volume10
DOIs
StatePublished - 2021

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