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[Display omitted] • OA is characterized by a progressive loss of tissue homeostasis due to senescent cell accumulation within the joints and bones. • Circulating proteomic, metabolic factors, as well as microRNAs, could affect both senescence and osteoarticular tissue homeostasis leading to OA development. • Some factors might be protective (GDF-11, alpha Klotho) or detrimental (GREM1, ROS, Chi3L1, miR-34a) regarding joint or bone tissue. Recent discoveries reveal that the chronic presence of senescent cells in osteoarticular tissues provides a focal point of disease development for osteoarthritis (OA). Nevertheless, senescence-regulatory factors associated with OA still need to be identified. Furthermore, few diagnostic- and prognostic-validated biochemical markers (biomarkers) are currently used in clinics to evaluate OA patients. In the future, alongside imaging and clinical examination, detecting senescence-regulatory biomarkers in patient fluids could become a prospective method for disease: diagnosis, monitoring, progression and prognosis following treatment. This review summarizes a group of circulating OA biomarkers recently linked to senescence onset. Remarkably, these factors identified in proteomics, metabolomic and microRNA studies could also have deleterious or protective roles in osteoarticular tissue homeostasis. In addition, we discuss their potentially innovative modulation in combination with senotherapeutic approaches, for long-lasting OA treatment. [ABSTRACT FROM AUTHOR]