Novel senolytics in frailty and bone regeneration

Senescent cells, which accumulate in various tissues and organs during the natural human aging process, are a driving force behind many age-related diseases and disorders. Active ingredients that selectively eliminate aged cells, so-called "senolytics", have been able to weaken or delay the onset or development of almost all age-related diseases in numerous animal experiments. Since the majority of these senolytics are associated with severe side effects and are often only effective in certain cell typesissues, there is a great need for new active ingredients with a better toxicological profile and improved efficacy. We recently observed a highly altered lipid metabolism in aged cells that seems predestined as a target of senolytic drugs. By inhibiting arachidonic acid degradation, we were able to eliminate senescent cells in cell culture. Based on these data, we will now test our hypothesis that inhibition of arachidonic acid metabolism can eliminate aged cells from various organs and tissues of naturally aged mice. We expect this to result in an increased tissue regeneration potential, which we will examine using bone regeneration as a model. We will also investigate the impact on frailty of preclinical models. The aim is to enable a maximum health span without extended suffering from age-associated diseases.