What is Senolytics:
Senolytics is a special class of drugs designed specifically for anti-aging. Senolytic drugs achieve this by targeting aging cells. Senescent Cells are cells that deteriorate with age and are a major cause of age-related diseases. The research into senolytics is to develop treatments that can effectively target specific senescent cells and integrate it into clinical use.
The Science of Cellular Senolytics:
Senescent cells develop naturally even in children. The aging mechanics of Senescent cells is dramatic including epigenetic, genomic, and mitochondria deterioration. This is when the cell is in a cell arrest not continuing further in the cell cycle. This stage is often triggered by carcinogenic exposure as well as UV. These cellular changes will translate into different protein changes that can cause the diseases associated with the new protein change. Some of the most common symptoms include frailty, cognitive impairment, and weakened immunity. Research has shown that senolytics can alleviate these symptoms, including mitochondrial dysfunction which was seen in animal test modules.
SASP Phenotype:
The question remains: how do Senescent cells develop with such damage without undergoing apoptosis? Apoptosis is a cellular safety mechanism designed to prevent the proliferation of cancerous cells. Some Senescent cells develop a phenotype abbreviated SASP, that upregulates apoptosis BCL-2 proteins. Thishis activated protein allows the cell to develop regardless of the cytotoxic environment. The SASP phenotype is a positive feedback loop as it can cause non senescent cells to become senescent through cell signaling.
Although this may seem concerning, there are thresholds that each person can have before the Senescent cells start to develop into an actual disease. Typically, the human immune system has been great at maintaining a normal level of senescent cells.
Treatments:
A common senescent cell treatment is a type of chemotherapy called CAR T-cell therapy. This involves scientists engineering white blood cells to target specific cells. The issue is specifically targeting SASP senescence cells and the weakened immune system that comes with CAR T-cell therapy.
Though the development of Senolytic drugs is slowly improving, the knowledge behind the mechanics of senescent cells have greatly increased in the last 10 years. Developing the research may open a window into true anti aging medicine that can cure what we imagine currently as incurable.
References
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022). Cellular senescence and senolytics: the path to the clinic. Nature Medicine, 28(8), 1556–1568. https://doi.org/10.1038/s41591-022-01923-y
Ageing and health. (2022, October 1). https://www.who.int/news-room/fact-sheets/detail/ageing-and-health
St Sauver, J. L., Boyd, C. M., Grossardt, B. R., Bobo, W. V., Rutten, L. J. F., Roger, V. L., Ebbert, J. O., Therneau, T. M., Yawn, B. P., & Rocca, W. A. (2015). Risk of developing multimorbidity across all ages in an historical cohort study: differences by sex and ethnicity. BMJ Open, 5(2), e006413. https://doi.org/10.1136/bmjopen-2014-006413
Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L. (2014). Frailty in childhood cancer survivors. Cancer, 121(10), 1540–1547. https://doi.org/10.1002/cncr.29211
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