There may be other methods than drugs to destroy senescent cells, which accumulate with age. The immune system fails as we age, and rejuvenating it may be another route to removing harmful, pro-aging senescent cells.

Senescent cells and senolytics

As your body ages, increasing amounts of your cells enter into a state of senescence. Senescent cells do not divide or support the tissue of which they are a part; instead, they emit a range of potentially harmful chemical signals, which encourage other nearby cells to also enter the same senescent state.

Their presence causes many problems: they degrade tissue function, increase chronic inflammation, and can even eventually raise the risk of cancer. Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of these senescent cells escape this process and accumulate.

One possible solution to this problem is to remove senescent cells in order to improve tissue regeneration and health. A class of drugs called senolytics focuses on the destruction of these stubborn “death-resistant” cells from the body, thus reducing inflammation and improving tissue function.







However, in biology, there is often more than one way to deal with a problem, and it could be the same for senescent cells.

Immunosurveillance and future immunotherapy

Today, we wanted to spotlight a new publication that discusses the possibility of removing senescent cells by using the immune system itself rather than senolytic drugs that encourage these cells to destroy themselves.

This is a logical idea given that during normal, healthy operation, the immune system does indeed detect and remove senescent cells; it is only as we age that this system breaks down and fails, leading to the accumulation of senescent cells, which are partially responsible for aging.

Abstract In response to persistent DNA damage, induction into cell senescence promotes an immunogenic program which facilitates immune clearance of these damaged cells. Under physiological conditions, senescent cells can activate both innate and adaptive immune responses, functioning to maintain tissue homeostasis. In addition, emerging findings suggest that programmed induction of cell senescence may be important for regulating reproductive processes, partly facilitated by immune clearance. However, likely owing to ageing of the immune system, a failure to eliminate senescent cells can contribute to their persistence in tissues, leading to the development and progression of age-related diseases. Such immune failure may in part be due to activation of the senescence program in immune cells, leading to their dysfunction. Furthermore, senescent cells under certain biological contexts have been shown to instead promote immune suppression, a response that may reflect differences between an acute versus chronic senescent phenotype. In this review, we provide an overview of the research to date concerning senescence immunosurveillance, including a focused discussion on the mechanisms by which macrophages may recognise senescent cells. Senescence immunotherapy strategies as an alternative to senolytics for the removal of senescent cells will also be discussed.

The authors of this review are Dominick Burton and Alexandra Stolzing. Alexandra is the chief researcher of the Major Mouse Testing Program, a senolytic project and the second project we hosted at lifespan.io.







Immunotherapy, as the authors suggest here, might be used to boost the aging immune system so that it can seek and destroy senescent cells more efficiently. This is a potential alternative path to using senolytic drugs and therapies to remove senescent cells.

Certainly, the immune system can remove senescent cells but ceases to do so as we age, so another possible route to take would be to rejuvenate the immune system as a whole. Increasing the production of immune cells by regeneration of the thymus is one example of this more general approach, and researchers are currently working on it.

Conclusion

There is rarely a single solution to a problem in biology, and it is good to see researchers exploring other potentially effective routes to removing senescent cells. Given that immunotherapy is progressing rapidly for cancer treatment, it may be possible to adapt this progress to senescent cells, as the two are related in their mechanics.

Literature







[1] Burton, D. Stolzing, A. (2018). Cellular senescence: Immunosurveillance and future immunotherapy. Science direct doi.org/10.1016/j.arr.2018.02.001