PXD027458-1

PXD027458 is an original dataset announced via ProteomeXchange.

Title	Age-Related Disruption of the Proteome and Acetylome in Mouse Hearts Correlates with Differential Loss of Function that is Attenuated by SS-31 and NMN
Description	We analyzed the effects of aging on protein abundance and acetylation, as well as the ability of the mitochondrial-targeted drugs SS-31 and NMN to reverse age-related changes, in mouse hearts. Both drugs had a modest effect on restoring the abundance and acetylation of proteins that are lost with age but only NMN reduced acetylation in a subset of proteins which increased acetylation with age. Primarily, these age-related increases in protein acetylation were in mitochondrial pathways such as mitochondrial dysfunction, oxidative phosphorylation, and TCA cycle signaling. We further assessed how these age-related changes correlated with diastolic function (Ea/Aa) and systolic function (fractional shortening under higher workload) measurements from echocardiography. These results show that diastolic and systolic function in old age correlate inversely with the abundance of a specific subset of proteins. This could indicate that the heart proteome may adapt to preserve diastolic or systolic function with age but cannot preserve both. This adds further evidence to our previous report that SS-31 provides benefit to diastolic function and NMN to systolic function and that the greatest benefit may be when both are administered together, as the combination provides a mechanism to improve both aspects of heart function simultaneously.
HostingRepository	PanoramaPublic
AnnounceDate	2022-08-02
AnnouncementXML	Submission_2022-08-02_14:59:38.645.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Richard Johnson
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Acetyl; Carbamidomethyl; Oxidation; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-20 23:56:58	ID requested
⏵ 1	2022-08-02 14:59:39	announced

Whitson JA, Johnson R, Wang L, Bammler TK, Imai SI, Zhang H, Fredrickson J, Latorre-Esteves E, Bitto A, MacCoss MJ, Rabinovitch PS, 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. Geroscience, 44(3):1621-1639(2022) [pubmed]

submitter keyword: Acetyl-lysine, post translational modifications, targeted proteomics, mitochondria, aging, heart

Peter S. Rabinovitch
contact affiliation	University of Washington, Department of Pathology
contact email	petersr@u.washington.edu
lab head
Richard Johnson
contact affiliation	University of Washington, Department of Genome Sciences
contact email	rj8@uw.edu
dataset submitter

Panorama Public dataset URI