The Useful Functions of Senescent Cells

Cells that become senescent cease to replicate and begin to secrete a pro-growth, pro-inflammatory mix of signals. Senescent cells do perform useful functions in the body, usually emerging for a short time before being cleared. It is only when senescent cells linger, accumulating to provoke disruption of tissue structure and immune function, that their presence becomes a harmful contribution to degenerative aging. Thus constant clearance of senescent cells is probably not the desired goal for medical science, but rather periodic clearance of the excess senescent cells via intermittent treatment with senolytic drugs, or some form of restoration of lost immune function in older individuals in order to allow the body to clear excess senescent cells in a timely fashion.

The aging of the world's population has intensified interest in understanding the aging process and devising strategies and interventions to prolong a healthy life span. Cellular senescence, when cells become irreversibly growth arrested after a period of in vitro cell proliferation or in response to sublethal stress or oncogene expression, plays a role in aging phenotypes and age-associated diseases. Increasing evidence shows that senescent cells also have essential physiological functions, such as in tumor suppression, development, wound healing, tissue remodeling, regeneration, and vasculature. This raises important questions about the similarities and differences between senescent cell types and how they function in homeostasis and pathology, and it creates additional challenges in targeting them therapeutically.

Although several studies in mouse models support the hypothesis that senescent cells can trigger or contribute to age-associated phenotypes, more recent studies have revealed additional roles for senescent cells in nonharmful and even physiological processes. Indeed, eliminating senescent cells in mice can be detrimental to health, highlighting the importance of these cells in mammalian homeostasis and physiology. For example, senescent cells become more prevalent with age, particularly in the liver, and are often vascular endothelial cells. The continuous or acute removal of these senescent cells in mice disrupted blood-tissue barriers and led to the buildup of blood-borne macromolecular waste, resulting in perivascular fibrosis in a variety of tissues and subsequent health deterioration.

Although damage and stress can induce cellular senescence, perhaps to recruit immune cells through the senescence-associated secretory phenotype (SASP) and promote tissue repair and remodeling, cellular senescence can also arise independently of molecular damage or injury, for example, during development. Furthermore, senescence induced by injury can encourage regeneration and wound healing, and the degree of senescent cell involvement in the regeneration of different tissues is an exciting avenue for future research. Although a role for senescent cells in aging has been suggested by many studies, the recent findings that demonstrate normal physiological functions of senescent cells reveal a more complicated picture of the potential role of cellular senescence in mammalian aging.


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