Accumulation of senescent cells leads to numerous diseases, such as osteoarthritis (OA). In this study, we set out to characterize heterogeneity of cellular senescence in aged articular cartilage and explored the presence of corresponding metabolic profiles in blood that could function as representative biomarkers. Hereto we set out to perform cluster analyses, using a gene-set of 131 senescence genes (N=57) in a previously established RNA sequencing dataset of aged articular cartilage, and a generated metabolic dataset in overlapping blood samples.

Using unsupervised hierarchical clustering and pathway analysis, we identified two cellular senescent endotypes in articular cartilage. Endotype-1 was enriched for cell proliferating pathways, while endotype-2 showed enriched inflammation associated pathways,

Notably, metabolic profiles in overlapping blood samples (N=21), showed two corresponding metabolic clusters in blood. These metabolic profiles could function as biomarkers for patient-tailored targeting of senescence in OA patients.

Read the whole publication: Identified senescence endotypes in aged cartilage are reflected in the blood metabolome (Boone I et al., GeroScience, 2023).