Dr. Lizzy Ostler, University of Brighton

There is growing evidence that many of the deleterious processes of ageing, such as heart disease, dementia and arthritis, could be prevented or remediated by simple chemical compounds. Recent work has demonstrated that the removal or alteration of phenotype of senescent cells has the potential to reduce multiple age-related pathologies. The development of orally-available broad-spectrum anti-degenerative medicines is now a realistic goal. A wide variety of polyphenolic natural products, often isolated from “super-foods” including grapes and cocoa beans, have long been identified as potential lead compounds for anti-ageing therapeutics. However, many such compounds have multiple biological activities, and may be poorly absorbed. We have established simple, robust and high-yielding syntheses to facilitate access to a broad range of structural variants of compounds based on Resveratrol, and subjected this panel of “Resveralogues” to a wide variety of in vitro assays, with a particular focus on activities related to cell growth and senescence. A subset of our compounds is able to “rejuvenate” cultures of senescent cells by altering RNA splicing patterns, lengthening telomeres, and enabling a significant fraction of cells to re-enter normal cell cycle. The implications of this novel mechanism for the design of future anti-degeneratives will be presented.