Open AccessAge-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
Author(s) -
Jeremy Whitson,
Richard S. Johnson,
Lu Wang,
Theo K. Bammler,
Shin–ichiro Imai,
Huiliang Zhang,
Jeanne Fredrickson,
Elena Latorre-Esteves,
Alessandro Bitto,
Michael J. MacCoss,
Peter S. Rabinovitch
Publication year - 2022
Publication title -
geroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.883
H-Index - 63
eISSN - 2509-2715
pISSN - 2509-2723
DOI - 10.1007/s11357-022-00564-w
Subject(s) - acetylation , nicotinamide mononucleotide , mitochondrion , phosphorylation , sarcopenia , function (biology) , medicine , oxidative phosphorylation , senescence , endocrinology , biology , biochemistry , microbiology and biotechnology , chemistry , nad+ kinase , nicotinamide adenine dinucleotide , enzyme , gene
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.