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In vivo analysis of γH2AX+ cells in skeletal muscle from aged and obese humans
Author(s) -
Dungan Cory M.,
Peck Bailey D.,
Walton R. Grace,
Huang Zhengyan,
Bamman Marcas M.,
Kern Philip A.,
Peterson Charlotte A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000111rr
Subject(s) - skeletal muscle , senescence , biology , myocyte , myogenesis , dna damage , microbiology and biotechnology , endocrinology , genetics , dna
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.