Written by Subikshaa S
Have we finally found the fountain of youth to make ourselves immortal?..Maybe..Maybe not.
Have you ever wondered if you can claim juvenility again?……… Well, it’s possible with a new class of drugs called “Senolytics”. Firstly, cellular senescence is the process that causes aging. Then, these senescent cells self-destruct through apoptosis process along with the immune system. With age, this system weakens and the senescent cells pile up and thus secretes Senescence-Associated Secretory Phenotype (SASP), which causes aging. The SASP note-worthily comes up with aging as well as certain types of cancer, ameliorating cancer metastasis. Thus, the removal of SASP along with Senolytics serves good for improving health and longevity. Senolytic therapies that selectively destroy senescent cells are the first rejuvenation therapies, a different kind of treatment whose objective is to point the root cause of aging and other age-related disorders.
The Senolytics target the senescent cells only and not any other receptors or biochemical substances by inducing the apoptosis of these cells. The unconventional strategies for developing Senolytic drugs have similarities with slants of developing antibiotics rather than the traditional one-target / one-drug / one-disease drug development method.
The dual combo of drugs namely the Dasatinib and Quercetin was noticed to target particular sensitivities of pro-survival pathways identified in senescent cells known as Senescent Cell Anti-Apoptotic Pathways (SCAPs). Also, it decreases the number of senescent cells in multiple tissues, and thus, the naturally aged cells improve efficiency in them. Then on, this combo is used along with compounds such as Fisetin, Navitolax, and other Senolytics. These tend to accomplish effects such as improved cardiac ejection fraction, regeneration, enhanced vascular calcification, improved pulmonary function in mice.
The combo is found efficacious only at an administration rate of once per week since its persistent presence is not required. A brief disruption of pro-survival pathways will suffice to kill senescent cells in mice as well as human cell culture. In mice, if administered monthly is as effective as daily administrations to subside age-related osteoporosis, thus bringing down the chances of potential side effects. Further studies show that removal of only thirty percent of the senescent was sufficient to bring down age-related decline. These outcomes offer much feasibility in selectively ablating senescent cells, thus increasing the efficiency of Senolytic drugs.
Although Senolytics may help increase health and longevity, delay aging, prevent various diseases, this hasn’t yet reached a stage of complete certainty. We ought to get more information about the safety, tolerability, side effects, and target engagement in human. There can be possibilities for severe, unexpected short, and long term effects to emerge. There is an ethical concern in conducting clinical trials and due to the emerging need to determine the efficacy of these rugs, conducting small trials in series. Preclinical and clinical studies are a must for each indication, so as to regulate the frequency of Senolytic administrations, to identify the best Senolytic agents or combinations for a particular type of disease. At this juncture, the use of Senolytic drugs should be confined to carefully monitored, controlled clinical trials.
References:
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939651/
- https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15264
- https://myramblingtoughts.weebly.com/blog/senolytics-or-the-search-for-a-longer-healthier-life
- https://www.lifespan.io/news/senolytics/
- https://www.nature.com/articles/s41591-018-0141-4?proof=t
- http://www.longlonglife.org/en/transhumanism-longevity/anti-aging-supplements/senolytics-the-war-on-senescence-is-on/
