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Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes
Aging Cell. 2024 May 6:e14113. doi: 10.1111/acel.14113.
William S Hambright 1, Victoria R Duke 1, Adam D Goff 1, Alex W Goff 1, Lucas T Minas 1, Heidi Kloser 1, Xueqin Gao 1, Charles Huard 1, Ping Guo 1, Aiping Lu 1, John Mitchell 1, Michael Mullen 1, Charles Su 1, Tamara Tchkonia 2, Jair M Espindola Netto 2, Paul D Robbins 3, Laura J Niedernhofer 3, James L Kirkland 2 4, Chelsea S Bahney 1 5, Marc Philippon 1 6, Johnny Huard 1
Abstract:
...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.
PMID: 38708778
Free Full-Text: https://onlinelibrary.wiley.com/doi/10.1111/acel.14113