Senescent cells accumulate with age and contribute to degenerative aging by provoking inflammation and disrupting tissue structure and function. Targeting cellular senescence for the treatment of age-related disease is presently in the slow, optimistic phase of research and development that comes after the initial hype has died down, but before a large number of attempts have been made at definitive, sizable clinical trials. This can last for years. The clinical development of new therapies is a very slow business. It has been something like fifteen years since the first flush of real excitement about senescent cells as a mechanism of aging captured the research community, and while a dozen or more life science companies are developing drugs to destroy or alter the behavior of senescent cells in patients, only a few small clinical trials have been conducted to date.
With the intensification of global aging, the incidence of age-related diseases (including cardiovascular, neurodegenerative, and musculoskeletal disorders) has been on the rise, and cellular senescence is identified as the core driving mechanism. Cellular senescence is characterized by irreversible cell cycle arrest, which is caused by telomere shortening, imbalance in DNA damage repair, and mitochondrial dysfunction, accompanied by the activation of the senescence-associated secretory phenotype (SASP).
In this situation, proinflammatory factors and matrix-degrading enzymes can be released, thereby disrupting tissue homeostasis. This disruption of tissue homeostasis induced by cellular senescence manifests as characteristic pathogenic mechanisms in distinct disease contexts. In cardiovascular diseases, senescence of cardiomyocytes and endothelial cells can exacerbate cardiac remodeling. In neurodegenerative diseases, senescence of glial cells can lead to neuroinflammation, while in musculoskeletal diseases, it can result in the degradation of cartilage matrix and imbalance of bone homeostasis.
This senescence-mediated dysregulation across diverse organ systems has spurred the development of intervention strategies. Interventional strategies include regular exercise, caloric restriction, senolytic drugs (such as the combination of dasatinib and quercetin), and senomorphic therapies. However, the tissue-specific regulatory mechanisms of cellular senescence, in vivo monitoring, and safety-related clinical translational research still require in-depth investigation.
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