학술논문
Age-related disruption of the proteome and acetylome in mouse hearts is associated with loss of function and attenuated by elamipretide (SS-31) and nicotinamide mononucleotide (NMN) treatment.
Document Type
Academic Journal
Author
Whitson JA; Department of Biology, Davidson College, 405 N Main St, Davidson, NC, 28035, USA.; Johnson R; Department of Genome Sciences, University of Washington, 3720 15th Street NE, Seattle, WA, 98195, USA.; Wang L; Department of Environmental & Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, 98105, USA.; Bammler TK; Department of Environmental & Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, 98105, USA.; Imai SI; Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.; Zhang H; Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA.; Fredrickson J; Department of Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA.; Latorre-Esteves E; Department of Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA.; Bitto A; Department of Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA.; MacCoss MJ; Department of Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA.; Rabinovitch PS; Department of Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA. petersr@u.washington.edu.
Source
Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101686284 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2509-2723 (Electronic) Linking ISSN: 25092723 NLM ISO Abbreviation: Geroscience Subsets: MEDLINE
Subject
Language
English
Abstract
We analyzed the effects of aging on protein abundance and acetylation, as well as the ability of the mitochondrial-targeted drugs elamipretide (SS-31) and nicotinamide mononucleotide (NMN) to reverse aging-associated changes in mouse hearts. Both drugs had a modest effect on restoring the abundance and acetylation of proteins that are altered with age, while also inducing additional changes. Age-related increases in protein acetylation were predominantly in mitochondrial pathways such as mitochondrial dysfunction, oxidative phosphorylation, and TCA cycle signaling. We further assessed how these age-related changes associated with diastolic function (Ea/Aa) and systolic function (fractional shortening under higher workload) measurements from echocardiography. These results identify a subset of protein abundance and acetylation changes in muscle, mitochondrial, and structural proteins that appear to be essential in regulating diastolic function in old hearts.
(© 2022. The Author(s), under exclusive licence to American Aging Association.)
(© 2022. The Author(s), under exclusive licence to American Aging Association.)