Cellular senescence is a state of permanent cell cycle arrest, meaning the cell can no longer divide and proliferate. It's a complex process that can be triggered by a variety of factors, including DNA damage, oxidative stress, telomere shortening, and oncogenic signals. Senescence is thought to have evolved as a protective mechanism to prevent the proliferation of damaged or potentially cancerous cells.
Senescent cells are not merely inactive; they undergo significant changes in their metabolism and function. They often enlarge, develop a flattened morphology, and exhibit changes in gene expression and protein production. Importantly, senescent cells secrete a variety of molecules, including cytokines, growth factors, and proteases, in a phenomenon known as the senescence-associated secretory phenotype (SASP). The SASP can have various effects on the surrounding tissue, including inflammation, tissue remodeling, and the modulation of immune responses.
While senescence can be beneficial in certain contexts, such as wound healing and embryonic development, it can also contribute to aging and age-related diseases. The accumulation of senescent cells in tissues over time can lead to chronic inflammation and tissue dysfunction, contributing to conditions such as osteoarthritis, atherosclerosis, and Alzheimer's disease.
In the context of fibroblasts, senescence can lead to changes in the production and organization of the extracellular matrix, which can affect tissue structure and function. For example, senescent fibroblasts often produce excessive amounts of certain extracellular matrix components, contributing to the thickening and stiffening of tissues, a common feature of aging.
There is currently a lot of interest in developing strategies to selectively eliminate senescent cells, a concept known as senolytics, or to modulate the SASP, as a way to combat aging and age-related diseases. However, this is a complex task, as not all senescent cells are harmful, and they can have beneficial roles in certain contexts. Therefore, a better understanding of the biology of senescence is needed to exploit it for therapeutic purposes.