Fig. 2

Aged-related changes on bone cell. During the ageing process, BMSCs experience ageing, which triggers the activation of NF-κB, leading to ROS production, thereby inhibits osteoblast precursor differentiation. This phenomenon is further exacerbated by elevated levels of CCL2 and CCL5, which contribute to the ageing of osteoblasts. Moreover, the decline in the levels of Sirt in aged MSCs promotes adipocyte differentiation. This results in an increase in ROS levels, leading to adipocyte ageing. This, in turn, contributes to secondary ageing in osteoblasts and vascular cells. The cumulative effect of these changes includes increased production of inflammatory cytokines and reduced oxygen availability in the vasculature, resulting in vascular stiffness and a disruption of blood flow within the bone microenvironment. Furthermore, a deficiency in molecular cathepsin K and integrins may lead to ageing in osteoclasts while preserving their bone resorption capacity