Senolytics as drugs or fashionable dietary supplements

Abstract

Abstract: Senolytics are a group of medicinal substances that selectively remove the so-called aging cells. The available theories indicate that these cells are resistant to apoptosis and accumulate at the causal sites of many chronic disorders and diseases, are metabolically active, and may acquire a pro-inflammatory, pro-apoptotic secretory phenotype that destroys healthy tissues. This results in the release of tissue-damaging proinflammatory cytokines, chemokines, and proteases. The most disturbing phenomenon is the innate immunity of aging cells to these factors. Aging cells undergo also metabolic changes, i.e. decreased use of fatty acids, increased glycolysis, and increased production of reactive oxygen species, which can affect other cells and even spread the aging process. Senolytic drugs (including Dasatinib, Quercetin, Fisetin, Navitoclax) have the ability to temporarily turn off the ability to defend against apoptosis. The senescent cells take weeks to accumulate again, so these substances can be given intermittently, reducing the likelihood of side effects. In preclinical models, it was shown that senolytics delay the processes of e.g. weakness, cancer, and dysfunction of the cardiovascular system, liver, kidneys, musculoskeletal system, lungs, eyes. However, ongoing clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer's disease, COVID-19, osteoarthritis, osteoporosis, and bone marrow transplantation have not yet been completed. Pending the results confirming the safety, tolerability, and efficacy of these substances, they cannot be used by patients until then. Despite this, many senolytic substances are now available in the form of dietary supplements. The pharmaceutical market and the production of dietary supplements are developing very dynamically, new technologies and new applications are constantly being discovered. However, supplements are not subject to any control as to the quality of the finished preparations and their composition, which may increase the danger of their use. By assumption, supplements contain ingredients that are supposed to support the functioning of our body, not to heal. Therefore, it is worth considering the need for supplementation, especially since supplements can be overdosed and may also react with drugs, which may have unforeseen effects.

Keywords

• senolytics
• dietary supplements
• dasatinib
• quercetin