Cellular Senescence

Cellular senescence is the process by which an organism’s cells cease to divide. In the case of cellular senescence, as opposed to apoptosis, the cells are damaged but are not eliminated by the body. Senescent cells are one of the hallmarks of aging. Scientists are studying how to eliminate cellular senescence in order to understanding its role in aging, tissue repair, and various age-related diseases. While senescence was initially considered a protective mechanism against cancer, emerging research suggests its involvement in a wide array of physiological and pathological processes.

What is Cellular Senescence?

Cellular senescence is a complex and multifaceted process that can be triggered by various intrinsic and extrinsic factors. It can be initiated in response to DNA damage, telomere shortening, oxidative stress, and other cellular stresses. Once triggered, cells enter a state of growth arrest, preventing further division and proliferation. Senescent cells also undergo morphological changes, such as enlarged and flattened cell shapes.

Senescent cells secrete a myriad of molecules collectively known as the senescence-associated secretory phenotype (SASP). SASP includes pro-inflammatory cytokines, growth factors, and matrix metalloproteinases, which can influence the surrounding microenvironment and neighboring cells. While SASP can contribute to tissue repair and inflammation resolution in the short term, persistent senescent cell accumulation can lead to detrimental effects over time.

Cellular Senescence and Aging

One of the primary focuses of research on cellular senescence is its association with aging. As organisms age, the number of senescent cells tends to increase in various tissues. This accumulation is believed to contribute to the decline in tissue function and the development of age-related diseases. Senescent cells can disrupt tissue homeostasis, impair regenerative capacity, and promote chronic inflammation, which are all hallmarks of aging.

Recent studies have shown that the removal of senescent cells, a process known as senolysis, can improve tissue function and extend lifespan in animal models. This has led to the development of senolytic drugs that selectively target and eliminate senescent cells. While the application of senolytics in humans is still in its early stages, the potential for mitigating age-related diseases and promoting healthy aging is promising.

Cellular Senescence and Disease

Beyond aging, cellular senescence has been implicated in the pathogenesis of various diseases, including cancer, neurodegenerative disorders, cardiovascular diseases, and metabolic disorders. In some cases, senescence may initially act as a protective mechanism by preventing the proliferation of damaged or potentially cancerous cells. However, persistent senescence can contribute to chronic inflammation and tissue dysfunction, ultimately exacerbating disease progression.

Therapeutic Implications

The recognition of cellular senescence as a key player in aging and disease has opened up new avenues for therapeutic interventions. Researchers are exploring strategies to modulate senescence, either by promoting the clearance of senescent cells or by manipulating the signaling pathways that regulate senescence. Senolytic drugs, senomorphic agents, and other innovative approaches are being developed to target cellular senescence and potentially delay aging and mitigate age-related diseases.