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

Jeremy A. Whitson, Richard Johnson, Lu Wang, Theo K. Bammler, Shin Ichiro Imai, Huiliang Zhang, Jeanne Fredrickson, Elena Latorre-Esteves, Alessandro Bitto, Michael J. MacCoss, Peter S. Rabinovitch

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1621-1639
Number of pages19
JournalGeroScience
Volume44
Issue number3
DOIs
StatePublished - Jun 2022

Keywords

  • Acetylomics
  • Aging
  • Elamipretide
  • Heart
  • Mitochondria
  • NMN
  • Proteomics
  • SS-31

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