Skip NavigationSkip to Content
Return Return to Search Results

Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction

  1. Author:
    Xie, Shaojun
    Choudhari, Sulbha
    Wu, Chia-Lung
    Abramson, Karen
    Corcoran, David
    Gregory, Simon G
    Thimmapuram, Jyothi
    Guilak, Farshid [ORCID]
    Little, Dianne [ORCID]

  2. Author Address

    Bioinformatics Core, Purdue University, West Lafayette, Indiana, USA., Advanced Biomedical Computational Science, Bioinformatics and Computational Science, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Center for Musculoskeletal Research, Department of Orthopaedics and Rehabilitation, University of Rochester, Rochester, New York, USA., Duke Molecular Physiology Institute, Durham, North Carolina, USA., Genomic Analysis and Bioinformatics Shared Resource, Duke Center for Genomic and Computational Biology, Duke University Medical Center, Durham, North Carolina, USA., Lineberger Bioinformatics Core, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA., Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA., Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, Missouri, USA., Shriners Hospitals for Children - St. Louis, St. Louis, Missouri, USA., Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA., Department of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.,
    1. Year: 2023
    2. Date: Mar
  2. Journal: FASEB Journal : official publication of the Federation of American Societies for Experimental Biology
    1. 37
    2. 3
    3. Pages: e22785
  4. Type of Article: Article
  5. Article Number: e22785
  1. Abstract:

    The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12-months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to the effects of age, but this was not true in obese mice. Functional pathway analyses identified a subset of genes with critical roles in progenitors and in diseases of obesity and aging. Specifically, Mapt, Nr3c2, App, and Ctnnb1 emerged as potential hypomethylated upstream regulators in both aging and obesity (AL vs. YL and AO vs. YO), and App, Ctnnb1, Hipk2, Id2, and Tp53 exhibited additional effects of aging in obese animals. Furthermore, Foxo3 and Ccnd1 were potential hypermethylated upstream regulators of healthy aging (AL vs. YL), and of the effects of obesity in young animals (YO vs. YL), suggesting that these factors could play a role in accelerated aging with obesity. Finally, we identified candidate driver genes that appeared recurrently in all analyses and comparisons undertaken. Further mechanistic studies are needed to validate the roles of these genes capable of priming ASCs for dysfunction in aging- and obesity-associated pathologies. © 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1096/fj.202201413R
  3. PMID: 36794668

Library Notes

  1. Fiscal Year: FY2022-2023
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel