Research in Progress Seminar - Shweta Yadav, PhD (Parkhitko Lab)

The next Aging Institute Research in Progress is scheduled for next Monday, October 19th from 12:00pm–1:00pm! Presenter Shweta Yadav, PhD (Parkhitko Lab) will be speaking on Methionine restriction promotes stress resistance and longevity through PRMT5 Location (In-Person ONLY): 5th Floor Board Room 100 Technology Drive, Pittsburgh, PA 15219 FREE PARKING: Guest parking is located at the front of the building. Please register your license plate at the security desk. FREE Pitt Shuttles FREE PIZZA in conference room Abstract: Methionine restriction (MetR) extends lifespan and improves metabolic health across species, but clinical translation is limited by poor dietary compliance and palatability. Methionine and ATP are the precursors for the production of S-adenosylmethionine (SAM), the principal and rate-limiting methyl donor used by methyltransferases (MTs). To determine which MTs exert beneficial effects similar to those of MetR, we performed a genetic screen of all MTs predicted in the Drosophila melanogaster genome. Notably, the top 10% of hits were enriched for protein arginine methyltransferases (PRMTs), implicating arginine methylation as a key regulatory node downstream of methionine metabolism. Among these, knockdown of PRMT5 significantly extended lifespan and enhanced resistance to starvation stress, and these effects were conserved in yeast and mammalian cells. Moreover, pharmacologic inhibition of PRMT5 in mice recapitulated key metabolic and frailty benefits of MetR. Using methylation-specific proteomic analyses, we identified proteins whose arginine-specific methylation was altered in response to inhibition of methionine metabolism or to csul/PRMT5 downregulation and whose knockdown promoted starvation resistance similar to that observed with MetR and csul/PRMT5 downregulation. In summary, we identified a novel mechanistic link between MetR, arginine methylation, and the beneficial effects of MetR that can be targeted with existing FDA-ap