Clinical validation of C 12 FDG as a marker associated with senescence and osteoarthritic phenotypes.

Autor: Hambright WS; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Duke VR; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Goff AD; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Goff AW; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Minas LT; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Kloser H; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Gao X; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Huard C; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Guo P; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Lu A; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Mitchell J; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Mullen M; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Su C; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA., Tchkonia T; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA., Espindola Netto JM; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA., Robbins PD; Department of Biochemistry and Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA., Niedernhofer LJ; Department of Biochemistry and Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA., Kirkland JL; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.; Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA., Bahney CS; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA.; Orthopaedic Trauma Institute, University of California San Francisco, San Francisco, California, USA., Philippon M; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA.; The Steadman Clinic, Vail, Colorado, USA., Huard J; Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, Colorado, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 May; Vol. 23 (5), pp. e14113. Date of Electronic Publication: 2024 May 06.
DOI: 10.1111/acel.14113
Abstrakt: 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 C 12 FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C 12 FDG + PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C 12 FDG + 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 C 12 FDG + 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 C 12 FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.
(© 2024 Steadman Philippon Research Institute. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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