Accepted_test

Study of geroprotective properties of urolithin A and its derivative with increased membranophilicity in vitro
by Maria Chelombitko | Galina Morgunova | Natalya Strochkova | Konstantin Lyamzaev | Anastasia Pavlyuchenkova | Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992 Russia; Russian Clinical and Research Center for Gerontology, Pirogov Russian National Research Medical University, Moscow, Russia | School of Biology, Moscow State University, Moscow, Russia | Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia | Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992 Russia; Russian Clinical and Research Center for Gerontology, Pirogov Russian National Research Medical University, Moscow, Russia | Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992 Russia; Russian Clinical and Research Center for Gerontology, Pirogov Russian National Research Medical University, Moscow, Russia
Abstract ID: 407
Event: BGRS-abstracts
Sections: Section “Genetics and systems biology of aging”

This study investigates the geroprotective properties of urolithin A and its enhanced membranophilic derivative, KIRS152, in vitro. Aging is characterized by mitochondrial dysfunction and cellular senescence, processes intricately linked and central to aging phenotypes. Mitophagy, responsible for eliminating dysfunctional mitochondria, is explored as a potential therapeutic avenue for age-related diseases. Urolithin A, derived from ellagic acid, shows promise as a geroprotective and antioxidant agent, despite minimal uncoupling activity. The study aims to enhance urolithin A uncoupling properties to augment mitophagy induction and efficacy. Through the synthesis of KIRS152, a derivative with increased membranophilicity, the study seeks to compare the geroprotective effects of both compounds in a model of cisplatin-induced aging in human skin fibroblasts.

Methods involve assessing cytotoxicity and evaluating the impact of non-toxic concentrations of urolithin A and KIRS152 on senescence markers induced by cisplatin. Senescent phenotype markers include lipofuscin autofluorescence, cell diameter, senescence-associated β-galactosidase activity, and GDF15 secretion. Results indicate KIRS152's superior geroprotective effects compared to urolithin A, manifested through reduced senescence index and SA-β-gal-positive cells. Moreover, KIRS152 prevents increased GDF15 secretion induced by cisplatin, while displaying lower toxicity. The study highlights the potential of KIRS152 as a more effective geroprotective agent than urolithin A, implicating mitophagy/autophagy in their mechanisms and suggesting KIRS152's promise for combating age-related diseases.