Catalyst Awardee

Project Description

Using Methioninase as a methionine restriction mimetic to delay aging and age-dependent diseases

Andrey Parkhitko, PhD | Aging Institute of UPMC and the University of Pittsburgh
Competition Sponsor
: US National Academy of Medicine
Awardee Year: 2023

Aging is a major risk factor for various human pathologies. The incidence of many chronic diseases including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases increases exponentially with age. Aging is characterized by the altered activity of different metabolic pathways. Targeting the metabolic pathways, whose activities are altered with age, has been shown to increase healthspan and delay the incidence of age-related diseases. The activity of methionine metabolism is dramatically altered during aging and under different age-dependent pathological conditions. Moreover, dietary methionine restriction (MetR) has been shown to extend health and lifespan in different species. However, it is very hard to implement MetR protocols in clinical practice due to the low palatability of MetR foods, which represents a major obstacle for bringing dietary MetR into clinical practice. This project aims to address this by using a bacterial enzyme, Methioninase, as a novel tool for the degradation of methionine and for delaying aging and age-dependent diseases. In this proposal, we will use a novel mouse model that will allow us to express Methioninase either in the whole body or in a tissue-specific manner. We will test whether degrading methionine is sufficient to prevent obesity in mice fed a high-fat diet or delay age-dependent deterioration of healthspan. The goal of this project is to test whether the benefits associated with dietary MetR could be achieved without limitations of methionine amounts in food by using Methioninase, which would then allow the use of this enzyme to delay aging in healthy individuals.

 

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