title: The metabolic footprint of aging in mice.
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.
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fe´de´rale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Riekelt H
authors.initials: RH
authors.lastname: Houtkooper
authors.forename: Carmen
authors.initials: C
authors.lastname: Argmann
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
authors.forename: Carles
authors.initials: C
authors.lastname: Cantó
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Jeninga
authors.forename: Pénélope A
authors.initials: PA
authors.lastname: Andreux
authors.forename: Charles
authors.initials: C
authors.lastname: Thomas
authors.forename: Raphaël
authors.initials: R
authors.lastname: Doenlen
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000375:Aging / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000596:Amino Acids / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009043:Motor Activity; D009132:Muscles / Q000378:metabolism; D010084:Oxidation-Reduction; D059467:Transcriptome
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D005227:Fatty Acids; D005947:Glucose