Senescent Cell

A Senescent Cell is a aberrant cell that has entered a permanent cell cycle arrest state.

• Context:
  • It can (typically) an Altered Cell, including both morphological and metabolic changes, reorganization of chromatin, differing gene expression, and the development of a pro-inflammatory conditions.
  • It can (typically) undergo replicative senescence, as observed in human fetal fibroblasts cultured in vitro, which reach a maximum of approximately 50 cell population doublings before becoming senescent.
  • It can (often) have both beneficial and harmful effects based on the situation.
  • It can (often) be recognized and removed by immune responses, such as natural killer (NK) cells and invariant Natural Killer T (iNKT) cells.
  • It can (often) involve a complex network of molecular pathways and cellular processes, including stress factors like oxidative stress, autophagy dysfunction, and abnormal cellular growth.
  • ...
• Example(s):
  • a Fibroblast, such as human fetal fibroblasts in culture that reach a maximum of approximately 50 cell population doublings before becoming senescent.
  • an Epithelial Cell in the skin that has suffered DNA damage due to ultraviolet (UV) radiation exposure and has entered a senescent state to prevent further damage and preserve tissue integrity.
  • ...
• Counter-Example(s):
  • a Malignant Cell.
• See: Cellular Senescence, Neurodegeneration, Cell Division, Hayflick Limit, Oxidative Stress, Autophagy, Carcinogenesis, Frailty Syndrome, Sarcopenia, Aging-Associated Disease.

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References

2023

• Web-Search Summary
  • A senescent cell is a cell that has entered a state of permanent cell cycle arrest, meaning it can no longer divide and proliferate. This condition often stems from DNA damage and was initially observed in human fetal fibroblasts, though it is now understood to generally affect non-transformed cells while transformed malign cells can reproduce indefinitely.

     Senescent cells experience several alterations, including both morphological and metabolic changes, reorganization of chromatin, differing gene expression, and the development of a pro-inflammatory condition known as the senescence-associated secretory phenotype (SASP). Senescence serves a complex role as it can have both beneficial and harmful effects based on the situation. On one hand, it has likely evolved to prevent damaged cells from turning cancerous. On the other hand, the accumulation of senescent cells through aging may contribute to various age-related diseases, including cancer, tissue degeneration, and inflammatory diseases.

    In addition, recent research has discovered the relationship between an immune response by natural killer (NK) cells to senescent cells. This response focuses on how NK cells can recognize and remove senescent cells, including senescent tumor cells. The process involves mechanisms like granule exocytosis, perforin, and granzyme, as well as the production of interferon-gamma (IFN-γ), by NK cells. When coupled with the role of SASP and the extracellular vesicles secreted by senescent cells, this can potentially stimulate macrophage activation and modulate NK cell functions.

    Furthermore, more advanced investigation reveals that invariant Natural Killer T (iNKT) cells can dispose of senescent cells, which are linked with aging and chronic diseases, under normal conditions. Nevertheless, factors like aging and obesity lessen iNKT cells' activity, leading to senescent cell accumulation.

    These discoveries provide potential therapeutic applications for age-related chronic diseases and fibrosis and diseases involving the accumulation of senescent cells in various tissues. Simultaneously, the Cellular Senescence Network (SenNet) Program seeks to comprehensively identify and profile senescent cells at various health states and lifespans, providing data and resources towards the development of therapeutics.

2023

• (Wikipedia, 2023) ⇒ https://en.wikipedia.org/wiki/Cellular_senescence Retrieved:2023-11-5.
  • Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. The physiological importance for cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. Senescent cells contribute to the aging phenotype, including frailty syndrome, sarcopenia, and aging-associated diseases. Senescent astrocytes and microglia contribute to neurodegeneration.

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