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PXD017706

PXD017706 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAcarbose improves late-life physical function in mice of both sexes, but rejuvenates cardiac structure and lipid profile in males only
DescriptionWith an expanding aging population burdened with comorbidities, there is considerable interest in treatments that optimize health in later life. Acarbose (ACA), a drug used clinically to treat Type 2 diabetes (T2DM) can extend mouse lifespan, with greater effect in males than in females. Utilizing a genetically heterogeneous mouse model, we tested the ability of ACA to ameliorate functional, pathological and biochemical changes that occur during aging, and determined which of the effects of age and drug were sex-dependent. In both sexes, ACA prevented age-dependent loss of body mass, in addition to improving grip strength, balance/coordination on an accelerating rotarod, and rotarod endurance. Age-related cardiac hypertrophy was seen only in male mice, and this male-specific aging effect was attenuated by ACA. ACA-sensitive cardiac changes were associated with reduced activation of cardiac growth promoting pathways and decreased abundance of peroxisomal proteins involved in lipid metabolism. ACA further ameliorated age-associated changes in cardiac lipid species, particularly lysophospholipids – changes which have previously been associated with aging, cardiac dysfunction and cardiovascular disease in humans. In the liver, ACA had pronounced effects on lipid handling in both sexes, reducing hepatic lipidosis during aging and shifting the liver lipidome in adulthood, particularly favoring reduced triglyceride accumulation. Our results demonstrate that ACA, already in clinical use for T2DM, has broad-ranging anti-aging effects in multiple tissues, and may have the potential to increase physical function and alter lipid biology to preserve or improve health at older ages.
HostingRepositoryPanoramaPublic
AnnounceDate2021-03-03
AnnouncementXMLSubmission_2021-03-03_09:13:55.846.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterGennifer Merrihew
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListCarbamidomethyl
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-02-24 16:14:54ID requested
12021-03-03 09:13:56announced
Publication List
Herrera JJ, Louzon S, Pifer K, Leander D, Merrihew GE, Park JH, Szczesniak K, Whitson J, Wilkinson JE, Fiehn O, MacCoss MJ, Day SM, Miller RA, Garratt M, Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology. JCI Insight, 5(21):(2020) [pubmed]
Keyword List
submitter keyword: data independent acquisition, Type 2 diabetes, acarbose, age-related disease
Contact List
Michael MacCoss
contact affiliationUniversity of Washington
contact emailmaccoss@uw.edu
lab head
Gennifer Merrihew
contact affiliationUniversity of Washington
contact emailgenn@uw.edu
dataset submitter
Full Dataset Link List
Panorama Public dataset URI