Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes

William S. Hambright, Victoria R. Duke, Adam D. Goff, Alex W. Goff, Lucas T. Minas, Heidi Kloser, Xueqin Gao, Charles Huard, Ping Guo, Aiping Lu, John Mitchell, Michael Mullen, Charles Su, Tamara Tchkonia, Jair M. Espindola Netto, Paul D. Robbins, Laura J. Niedernhofer, James L. Kirkland, Chelsea S. Bahney, Marc PhilipponJohnny Huard

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Original languageEnglish (US)
Article numbere14113
JournalAging cell
Volume23
Issue number5
DOIs
StatePublished - May 2024

Bibliographical note

Publisher Copyright:
© 2024 Steadman Philippon Research Institute. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Keywords

  • aging
  • cell senescence
  • osteoarthritis
  • senolytics

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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