Protection versus Harm: Cellular Senescence in the Context of Cancer
A little cellular senescence is a good thing. When a cell enters the state of senescence in response to potentially cancerous mutational damage it shuts down replication and secretes signals that attract the immune system. Immune cells destroy any such senescent, damaged, potentially dangerous cells that fail to destroy themselves. When senescent cells accumulate with age, however, as the immune system falters in its task of clearance, the inflammatory secretions of these errant cells - the senescence-associated secretory phenotype (SASP) - make the environment much more favorable for the creation and growth of cancer.
Cellular senescence provides a significant benefit to the host by inducing irreversible cell cycle arrest and eliciting potent immune-mediated incipient tumor cell clearance, which is characterized by reduced incidence of cancer and halted tumor development. Senescence provides an alternative strategy to overcome the limitations of traditional cancer treatment because low dose of drugs can achieve the purpose of inducing senescence. However, senescent cells and SASP components can directly or indirectly promote tumor cells growth, invasion, and metastasis, and tumor vascularization. The senescence phenotype is complicated, and the production rate and clearance rate of senescent cells may be the influencing factors of the effects of senescence on tumor progression. One of the possibilities is that senescent cells are only beneficial when they are transient, and the accumulation of senescent cells and SASP cause increased susceptibility to tumorigenesis.
The in-depth understanding and utilization of senescence in cancer therapy has gained increasing attention and has become an important research field. A growing number of studies have convincingly demonstrated a paradoxical role for spontaneous senescence and therapy-induced senescence (TIS), that senescence may involve both cancer prevention and cancer aggressiveness. Previous findings have indicated that TIS is a positive outcome of therapy, since senescence is a state of growth arrest reflecting the loss of reproductive potential. In order to overcome the negative effects of TIS in cancer treatment, the concept of combining senescence-inducing therapies and removal of senescent cells, both normal and tumor derived, via senolytic therapies, or manipulating the paracrine effects of SASP is proposed. However, before clinical application, we must balance the validity and potential risks, and determine the overall advantages of this treatment concept.
Hi, Will you send me independent research supporting the statement in Feb 21,2022 Fight Aging stating"Nevertheless sensescence is an essential anticancer mechanism and interfering with this can be associated with cancer development."You sent me a link from Fight Aging to support statement but I would like to see some independent research because I use senolytics and I do not want to risk cancer development
Christa
anti-cancer is cell cycle arrest and then elimination of such cells. When this mechanism partially failed (cell cycle stopped but the cell was not eliminated) the immediate cancer danger from this cell is temporarily stopped, but signalling from this cell have detrimental effect on immune system (which also cannot tell the difference between senescent cells and cancer cells and is aimed at removing all and becomes overwhelmed both from their number and from their signalling) and the body as a whole and the level of senescent cells in long term elevates the risk of cancer (being the factor correlated with cancer incidence risk). Equating 'senescent cells' with senescence as a process is equating the toxic waste of anti-cancer mechanism that failed (cause evolution found some other roles for such cells through built-in margin of their persistence) with "anti-cancer action", and is persistent misconception in this area. Someone chose wrong name for these cells long time ago... 'senescent cells' name is highly confusing, while it means pre-cancer/failed-to-be-cancer-cells-but-yet-highly-toxic.
https://onlinelibrary.wiley.com/doi/10.1111/acel.13314
"We simulated the effects of removing senescent cells on the incidence of a representative age-related disease. Similar conclusions are found for all age-related diseases. We used a conservative approach, by assuming that only 25% of the senescent cells are vulnerable to the treatment (Karin et al., 2019). Another way of viewing this is that the treatment can remove only 25% of the damaged cells associated with the disease incidence.
Treatment beginning at age 60, and given every 30 days, reduces disease [cancer] incidence by about tenfold within a year (Figure 5a). The incidence curve is shifted to lower values corresponding to an age that is about 25 years younger (Figure 5a). Prevalence of the disease until age 90 is reduced by about 80%."