My laboratory’s interest is how metabolism is reprogrammed with aging and how age-dependent metabolic changes can be targeted to extend health- and lifespan. Using Drosophila as a model system, we demonstrated that aging is characterized by extensive reprogramming of methionine metabolism and delayed processing of SAH, a competitive inhibitor of a broad spectrum of methyltransferases. In addition, we demonstrated that tyrosine metabolism is altered with age due to the activation of the tyrosine degradation pathway. Our goal is to determine how these metabolic pathways crosstalk to regulate the activity of methyltransferases (methionine metabolism) and the production of neuromediators (tyrosine metabolism). We are also interested in whether ‘resetting’ the methionine and tyrosine metabolic pathways back to a more youthful state can be translated to delay aging of higher organisms and improve phenotypes related to Alzheimer’s disease. In addition, we would like to introduce bacterial enzymes analogous to Methioninase that can provide novel metabolic functions to eukaryotic cells, and to repurpose CRISPR/Cas9 multiplex systems for simultaneous targeting of different metabolic pathways to achieve additive/synergistic effects on lifespan.

How can we combine targeting of different pro-longevity pathways to achieve additive/synergistic extension of health- and lifespan and how they can be translated into human beings?