Cells that become senescent cease to replicate and secrete inflammatory signals that are disruptive to tissue structure and function. This happens constantly throughout life, largely as the result of cells reaching the Hayflick limit on replication, but also as a result of stress, damage, or a toxic local environment. In youth, newly created senescent cells are cleared rapidly by the immune system. With age, this clearance is impaired and the number of senescent cells in every cell population increases, contributing to age-related dysfunction and disease.
In today's open access paper, researchers discuss the biochemistry and role of senescence in osteoblast cells and their contribute to osteoporosis, the age-related loss of bone mass and strength. Bone tissue is constantly remodeled, created by osteoblast cells and destroyed by osteoclast cells. With age, the balance of these activities shifts to favor osteoclasts, and thus a gradual loss of bone density is the result. An increase in senescence in the osteoblast population is one of the contributing causes of this outcome, and so therapies targeting senescent cells may help to slow the onset and progression of osteoporosis.
Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments
Studies have shown that osteoporosis is closely related to ageing and the senescence of osteoblasts in the bone microenvironment. Counteracting osteoblast senescence and balancing the differentiation, proliferation, and function of osteoclasts and osteoblasts will remain central to age-related osteoporosis research.
During ageing, osteoblast lineages undergo significant changes that affect their ability to form, maintain and repair bone. Osteoblast precursors, including mesenchymal stem cells, show decreased proliferative capacity and multifunctionality, resulting in impaired osteogenic differentiation potential. The biological behaviours and functions of senescence-related osteoblast lineages are regulated by a variety of signalling pathways associated with ageing, which may influence the cell cycle, oxidative stress response, and cell metabolism. In short, the proliferation ability of senescent osteoblast lineages is weakened, affecting the renewal and repair of bone tissue. Moreover, the mineralised bone formation process is also negatively affected by ageing, resulting in abnormal bone matrix formation and mineralisation. This further leads to an imbalance in bone homeostasis in the body and ultimately accelerates bone loss.
Anti-senescence interventions targeting osteoblasts could potentially revolutionise the treatment and prevention of osteoporosis. For instance, pharmacological agents that inhibit senescence-associated pathways, such as mTOR inhibitors or senolytics, have shown promise in preclinical studies by enhancing osteoblast function and bone formation. Similarly, lifestyle modifications, including CR and regular physical exercise, have been demonstrated to mitigate osteoblast ageing and improve bone health. Moreover, the development of novel biomarkers for osteoblast senescence could facilitate early diagnosis and personalised treatment strategies for osteoporosis.
View the full article at FightAging
