Aging and Ovariectomy Induces Parallel Phosphoproteomic Changes in Skeletal Muscle of Female Mice
08-15-2023“Our findings highlight key molecular signatures and pathways in contracted muscle [...] that may contribute to skeletal muscle strength loss due to estrogen deficiency.”
Listen to an audio version of this press release
BUFFALO, NY- August 15, 2023 – A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 15, entitled, “Natural aging and ovariectomy induces parallel phosphoproteomic alterations in skeletal muscle of female mice.”
The loss of skeletal muscle strength mid-life in females is associated with the decline of estrogen. In this new study, researchers Mina P. Peyton, Tzu-Yi Yang, LeeAnn Higgins, Todd W. Markowski, Kevin Murray, Cha Vue, Laurie L. Parker, and Dawn A. Lowe from the University of Minnesota questioned how estrogen deficiency might impact the overall skeletal muscle phosphoproteome after contraction, as force production induces phosphorylation of several muscle proteins.
“Importantly, identification of these altered phosphosites and candidate kinases and phosphatases sensitive to the presence of estrogen will help advance our understanding of the contributions of estrogen deficiency to muscle strength loss in aging females.”
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.
“In summary, our results from contracted skeletal muscle highlight CAST Ser-82 as a candidate phosphosite, and MAPK1/ERK2, PRKACA, and calcineurin as candidate upstream regulators sensitive to estrogen deficiency that may contribute to changes in the force-generating capacity of skeletal muscle.”
Read the full study: DOI: https://doi.org/10.18632/aging.204959
Corresponding Author: Dawn A. Lowe - lowex017@umn.edu
Keywords: estrogen deficiency, CAST, MAPK, PKA, calcineurin
Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204959
Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts
About Aging-US:
Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
Please visit our website at www.Aging-US.com and connect with us:
- X
- YouTube
- Spotify, Apple, SoundCloud, and available wherever you listen to podcasts
For media inquiries, please contact media@impactjournals.com.