Dr. Melanie R. McReynolds is a HHMI Hanna H. Gray postdoctoral fellow and Burroughs Wellcome Fund PDEP awardee at Princeton University, where her research focuses on the intersection of metabolic decline and aging. Melanie holds a B.S. degree in Chemistry and Physics from Alcorn State University. She participated in the NIH funded Alcorn State to Penn State Bridges to the Doctorate Program where she obtained her M.S. degree in Biological Sciences. Dr. McReynolds completed her Ph.D. in Biochemistry, Microbiology and Molecular Biology at the Pennsylvania State University. Melanie was recognized as a Rising Star on the CellPress list of Top 100 Inspiring Black Scientists in America and aims to inspire the next generation of scientists to trust that all things will work together for those who believe. Melanie is on the trajectory to establish her independent research group, where her future lab will shed light on metabolic aging and disease. She will return to Penn State as Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biochemistry and Molecular Biology—effective January 2022.
NAD+ flux is maintained in aged mice
NAD+ is an essential coenzyme found in all living cells. NAD+ concentrations decline during aging, but whether this reflects impaired production or accelerated consumption remains unclear. Here we employed isotope tracing and mass spectrometry to probe NAD+ metabolism across tissues in aged mice. In 25-month-old mice, we observe modest tissue NAD+ depletion (median decrease ~30%) without significant changes in circulating NAD+ precursors. Isotope tracing showed unimpaired synthesis of circulating nicotinamide from tryptophan, and maintained flux of circulating nicotinamide into tissue NAD+ pools. Although absolute NAD+ biosynthetic flux was maintained in most tissues of aged mice, fractional tissue NAD+ labeling from infused labeled nicotinamide was modestly accelerated, consistent with increased activity of NAD+ consuming enzymes. Thus, age-related decline in NAD+ is relatively subtle and driven by increased NAD+ consumer activity rather than impaired production.