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PXD064514-1

PXD064514 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSex-specific Phosphoproteome Responses to Calorie Restriction and Insulin in Skeletal Muscle from Older Rats
DescriptionAging impairs skeletal muscle insulin sensitivity, yet the underlying molecular mechanisms remain incompletely understood. Here, we examined how short-term caloric restriction (CR) alters muscle insulin action and signaling in aged rats (22 months old) of both sexes. After 8 weeks of CR or ad libitum feeding, we assessed insulin-stimulated glucose uptake (ISGU) ex vivo and performed deep phosphoproteomic profiling. CR enhanced ISGU in both sexes, with a more pronounced effect in females. Insulin-regulated phosphoproteomic responses were concordant between males and females, yet females exhibited more robust and widespread phosphorylation changes, potentially explaining their greater ISGU. CR induced extensive remodeling of basal muscle phosphorylation, particularly within structural and contractile pathways. Personalized phosphoproteomic analysis identified insulin-responsive sites on Leiomodin-1 (Lmod1) and EH domain-binding protein 1-like protein 1 (Ehbp1l1) that correlated with ISGU across individuals. Notably, Lmod1demonstrated strong genetic association with glycemic traits in humans, and several regulated sites overlapped with phosphosites observed in human clamp studies, reinforcing their translational relevance. Collectively, these findings reveal sex-dependent and diet-sensitive phosphosignaling mechanisms that modulate muscle insulin responsiveness during aging and nominate candidate regulatory nodes for future study.
HostingRepositoryPRIDE
AnnounceDate2025-11-24
AnnouncementXMLSubmission_2025-11-24_12:11:43.662.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSean Humphrey
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationListphosphorylated residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-06-02 07:25:20ID requested
12025-11-24 12:11:44announced
Publication List
Wang H, Madsen S, Needham EJ, Humphrey SJ, Zheng A, Arias EB, St, รถ, ckli J, Cutler HB, James DE, Cartee GD, Sex-specific phosphoproteome responses to calorie restriction and insulin in skeletal muscle from older rats. J Gerontol A Biol Sci Med Sci, 80(12):(2025) [pubmed]
10.1093/gerona/glaf231;
Keyword List
submitter keyword: calorie restriction, phosphoproteome, rats, skeletal muscle, muscle
Contact List
Sean Humphrey
contact affiliationFunctional Phosphoproteomics lab, Murdoch Children's Research Institute, Melbourne Australia
contact emailsean.humphrey@mcri.edu.au
lab head
Sean Humphrey
contact affiliationMurdoch Children's Research Institute
contact emailsean.j.humphrey@gmail.com
dataset submitter
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