Targeting senescent cells: approaches, opportunities, challenges
Cellular senescence, which is the hallmark of aging and is caused by a number of cell-autonomous processes as well as non-cell processes, has several consequences on an organism. Senescence has been linked to a number of processes, including tumor suppression, aging and development. The time they spend in the body is directly related to their positive or negative effects. Once they have completed their actions, immune cell are recruited to remove the senescent cells. In contrast, long-term (chronic) senescent cells are associated with disease; they secrete pro-inflammatory and pro-tumorigenic factors in a state known as senescence-associated secretory phenotype (SASP). Cellular senescence is the focus of treatment for aging-related illnesses. Current therapies are focused on elimination of senescent cell functions in three main ways: i) use of senolytics; ii) inhibition of SASP; and iii) improvement of immune system functions against senescent cells (immunosurveillance). Some anti-cancer treatments are also based on inducing senescence within tumor cells. These senescent cancer cells, however, must be cleared subsequently to avoid a pro-tumorigenic chronic state. The following is a list of possible scenarios based on the type of therapy, along with pros and cons for each.
Keywords: anti-aging therapy, immunosurveillance and cellular senescence.
Cellular senescence can be a stress response mechanism that is triggered by various insults including DNA damage, telomere loss, and cancerous mutations [1]. It was first described in human diploid cells after successive rounds division [2]. The main characteristics are an irreversible growth stop, changes to cell size and shape, increased lysosomal activities, anti-proliferative protein expression, resistance against apoptosis and activation of damage sensing signaling pathways. Another important characteristic is the regulated secretion of interleukins (ILs), inflammatory factors, chemokines, proteases and growth factors, termed the senescence-associated secretory phenotype (SASP) [3].
Source:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949083/
