The evidence is compelling for the age-related accumulation of senescent cells to be an important driving mechanism of degenerative conditions in bone tissue. As for many other age-related conditions, animal study data suggests that clearance of senescent cells via the use of senolytic therapies is a promising form of treatment for age-related dysfunction in bone tissue. Human data is arriving only slowly, and initially only in small clinical trials more focused on safety than efficacy. Few trials are being conducted for the first generation, low-cost senolytics such as the dasatinib and quercetin combination, because there is no financial incentive for the industry to pay for this work, while the clinical development of novel senolytics is proceeding at the usual glacial pace.
Cellular senescence and other age-related mechanisms synergistically lead to impaired bone cell function, facilitating the onset and progression of bone diseases, such as osteoporosis (OP), intervertebral disc degeneration (IVDD), and osteoarthritis (OA). Cellular senescence is a particular cellular state characterized by irreversible arrest of the cell cycle and the emergence of a distinctive senescence-associated secretory phenotype (SASP), which is one of the key mechanisms in the development and progression of skeletal diseases. In addition, other age-related mechanisms occur in the skeletal system that synergistically contribute to the development of bone diseases. For example, the impaired intercellular crosstalk leads to an abnormal accumulation of senescence phenotypes in the bone marrow, the generation of a disturbed microenvironment promotes senescence in the skeletal system.
The elderly population has a high prevalence of age-related bone diseases. Particularly in elderly individuals (aged 65 and above), age-related bone diseases represent the leading cause of disability worldwide. The associated pain and limited mobility lead to a decrease in quality of life, posing a significant healthcare burden to the government. Prospects for the development of drugs targeting skeletal aging diseases are currently not optimistic, largely owing to a lack of understanding of the cellular senescence and other age-related mechanisms that lead to bone dysfunction during aging. In this review, we summarize the current understanding of cellular senescence and other age-related mechanisms in the pathogenesis of bone diseases, highlighting the diversity of the mechanisms involved in cellular senescence within different skeletal aging microenvironments. Moreover, we provide an overview of therapeutic approaches involving selective elimination or the reversion of cellular senescence.
Link: https://doi.org/10.1038/s41413-025-00448-7
View the full article at FightAging
