The metabolic footprint of aging in mice

TLDR

Aging is marked by a decline in cellular function and widespread metabolic dysfunction, a hallmark observed across species. The study aimed to provide a comprehensive overview of metabolic changes in healthy aging mammals by comparing young and 2‑year‑old mice. Researchers integrated in‑vivo phenotyping, gene expression profiling, biochemical assays, and metabolomics to delineate the aging metabolic footprint. They identified disruptions in glucose, fatty acid, and redox pathways, with decreased long‑chain acylcarnitines, increased free fatty acids, and reduced plasma amino acids, establishing these metabolites as biomarkers of aging and healthspan.

Abstract

Aging is characterized by a general decline in cellular function, which ultimately will affect whole body homeostasis. Although DNA damage and oxidative stress all contribute to aging, metabolic dysfunction is a common hallmark of aging at least in invertebrates. Since a comprehensive overview of metabolic changes in otherwise healthy aging mammals is lacking, we here compared metabolic parameters of young and 2 year old mice. We systemically integrated in vivo phenotyping with gene expression, biochemical analysis and metabolomics, thereby identifying a distinguishing metabolic footprint of aging. Among the affected pathways in both liver and muscle we found glucose and fatty acid metabolism and redox homeostasis. These alterations translated in decreased long chain acylcarnitines and increased free fatty acid levels and a marked reduction in various amino acids in the plasma of aged mice. As such, these metabolites serve as biomarkers for aging and healthspan.