title: Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice.
abstract: Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age-related declines in physical function. Early evidence suggests that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age-related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large-scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post-translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age-related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti-inflammatory properties of n-3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti-inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n-3 PUFAs.
authors.affiliation: Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Johnson
authors.affiliation: Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Antigoni Z
authors.initials: AZ
authors.lastname: Lalia
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Surendra
authors.initials: S
authors.lastname: Dasari
authors.affiliation: Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Pallauf
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Fitch
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, CA, USA.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Hellerstein
authors.affiliation: Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Lanza
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
chemical_list: D024101:Mitochondrial Proteins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: aging; docosahexaenoic acid; eicosapentaenoic acid; mitochondria; omega 3; proteomics; sarcopenia