In vivo analysis of γH2AX+ cells in skeletal muscle from aged and obese humans

Cory M. Dungan, Bailey D. Peck, R. Grace Walton, Zhengyan Huang, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Over the past 20 years, various identifiers of cellular senescence have been used to quantify the abundance of these cells in different tissues. These include classic markers such as p16, senescence-associated β-gal, and γH2AX, in addition to more recent markers (Sudan Black B and HMGB1). In vivo data on the usefulness of these markers in skeletal muscle are very limited and inconsistent. In the present study, we attempted to identify senescent cells in frozen human skeletal muscle biopsies using these markers to determine the effects of age and obesity on senescent cell burden; however, we were only able to assess the abundance of DNA-damaged nuclei using γH2AX immunohistochemistry. The abundance of γH2AX+ cells, including satellite cells, was not higher in muscle from old compared to young individuals; however, γH2AX+ cells were higher with obesity. Additionally, terminally differentiated, postmitotic myofiber nuclei from obese individuals had elevated γH2AX abundance compared to muscle from lean individuals. Analyses of gene expression support the conclusion that the elevated DNA damage and the senescence-associated secretory phenotype are preferentially associated with obesity in skeletal muscle. These data implicate obesity as a larger contributor to DNA damage in skeletal muscle than aging; however, more sensitive senescence markers for human skeletal muscle are needed to determine if these cells are in fact senescent.

Original languageEnglish
Pages (from-to)7018-7035
Number of pages18
JournalFASEB Journal
Volume34
Issue number5
DOIs
StatePublished - May 1 2020

Bibliographical note

Funding Information:
The authors thank Drs. Ying Liang and Cuiping Zhang for their assistance with the cell irradiation experiments, and Dr Kevin Murach for the thoughtful discussions about this project. This research was supported by NIH grants AG049806 to CAP, PAK and MMB, AR060701 to CAP, and CTSA grant UL1 TR001998.

Publisher Copyright:
© 2020 Federation of American Societies for Experimental Biology

Keywords

  • DNA damage
  • postmitotic
  • satellite cells
  • senescence
  • γH2AX

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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