Research Paper Volume 15, Issue 15 pp 7362—7380
Natural aging and ovariectomy induces parallel phosphoproteomic alterations in skeletal muscle of female mice
- 1 Department of Rehabilitation Medicine, Division of Rehabilitation Science, University of Minnesota – Twin Cities, Minneapolis, MN 55455, USA
- 2 Department of Computer Science, Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN 55455, USA
- 3 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota – Twin Cities, Minneapolis, MN 55455, USA
- 4 Department of Rehabilitation Medicine, Division of Physical Therapy, University of Minnesota – Twin Cities, Minneapolis, MN 55455, USA
Received: December 27, 2022 Accepted: July 24, 2023 Published: August 14, 2023
https://doi.org/10.18632/aging.204959How to Cite
Copyright: © 2023 Peyton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The loss of skeletal muscle strength mid-life in females is associated with the decline of estrogen. Here, we questioned how estrogen deficiency might impact the overall skeletal muscle phosphoproteome after contraction, as force production induces phosphorylation of several muscle proteins. Phosphoproteomic analyses of the tibialis anterior muscle after contraction in two mouse models of estrogen deficiency, ovariectomy (Ovariectomized (Ovx) vs. Sham) and natural aging-induced ovarian senescence (Older Adult (OA) vs. Young Adult (YA)), identified a total of 2,593 and 3,507 phosphopeptides in Ovx/Sham and OA/YA datasets, respectively. Further analysis of estrogen deficiency-associated proteins and phosphosites identified 66 proteins and 21 phosphosites from both datasets. Of these, 4 estrogen deficiency-associated proteins and 4 estrogen deficiency-associated phosphosites were significant and differentially phosphorylated or regulated, respectively. Comparative analyses between Ovx/Sham and OA/YA using Ingenuity Pathway Analysis (IPA) found parallel patterns of inhibition and activation across IPA-defined canonical signaling pathways and physiological functional analysis, which were similarly observed in downstream GO, KEGG, and Reactome pathway overrepresentation analysis pertaining to muscle structural integrity and contraction, including AMPK and calcium signaling. IPA Upstream regulator analysis identified MAPK1 and PRKACA as candidate kinases and calcineurin as a candidate phosphatase sensitive to estrogen. Our findings highlight key molecular signatures and pathways in contracted muscle suggesting that the similarities identified across both datasets could elucidate molecular mechanisms that may contribute to skeletal muscle strength loss due to estrogen deficiency.