Senescent cell
Introduction
Senescent cells are cells that have lost their ability to divide and proliferate, a state known as cellular senescence. This is a natural part of the aging process and is a response to various forms of cellular stress, including DNA damage, oncogene activation, and telomere shortening. Senescent cells are not merely inactive; they undergo significant changes in their morphology, gene expression, and secretory profile, which can have profound effects on the surrounding tissue microenvironment.
Cellular Senescence
Cellular senescence is a state of irreversible cell cycle arrest that can be triggered by a variety of stressors. This includes DNA damage, oncogene activation, telomere shortening, and oxidative stress. Senescent cells are characterized by a number of phenotypic changes, including an enlarged, flattened morphology, increased granularity, and changes in gene expression and protein synthesis. They also develop a senescence-associated secretory phenotype (SASP), which involves the secretion of a variety of inflammatory and growth-promoting factors.
Senescence-Associated Secretory Phenotype (SASP)
The SASP is a major feature of senescent cells and has significant effects on the tissue microenvironment. It includes the secretion of a variety of factors, including cytokines, chemokines, growth factors, and proteases. These factors can have both autocrine and paracrine effects, influencing the behavior of both the senescent cells themselves and the surrounding non-senescent cells. The SASP can promote inflammation, tissue remodeling, and even tumorigenesis in some contexts.
Role in Aging and Disease
Senescent cells accumulate with age in many tissues, and their presence has been linked to a variety of age-related diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative diseases. The SASP can contribute to these diseases by promoting chronic inflammation, tissue damage, and tumorigenesis. However, senescent cells also have beneficial roles, such as in wound healing and tissue repair.
Senescence and Cancer
Senescence is a potent tumor suppressor mechanism, as it prevents the proliferation of cells with potentially oncogenic mutations. However, the SASP can also promote tumorigenesis by creating a pro-inflammatory microenvironment and stimulating the growth and survival of nearby cancer cells. This dual role of senescence in cancer is a topic of ongoing research.
Senescence in Tissue Repair and Regeneration
Senescent cells have been shown to play important roles in wound healing and tissue repair. They can promote tissue remodeling and regeneration through the SASP, which includes growth factors and proteases. However, the persistent presence of senescent cells and the SASP can also lead to chronic inflammation and tissue damage, contributing to aging and age-related diseases.
Therapeutic Targeting of Senescent Cells
Given the role of senescent cells in aging and disease, there is growing interest in developing therapies that can selectively eliminate these cells or modulate their SASP. Such therapies, known as senolytics and senomorphics, respectively, have shown promise in preclinical studies and are currently being tested in clinical trials.