PXD017706
PXD017706 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Acarbose improves late-life physical function in mice of both sexes, but rejuvenates cardiac structure and lipid profile in males only |
Description | With 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. |
HostingRepository | PanoramaPublic |
AnnounceDate | 2021-03-03 |
AnnouncementXML | Submission_2021-03-03_09:13:55.846.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Gennifer Merrihew |
SpeciesList | scientific name: Mus musculus; NCBI TaxID: 10090; |
ModificationList | Carbamidomethyl |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2020-02-24 16:14:54 | ID requested | |
⏵ 1 | 2021-03-03 09:13:56 | announced |
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 affiliation | University of Washington |
contact email | maccoss@uw.edu |
lab head | |
Gennifer Merrihew | |
contact affiliation | University of Washington |
contact email | genn@uw.edu |
dataset submitter |
Full Dataset Link List
Panorama Public dataset URI |