NIA Interlab: Defining the role of NAD+ depletion in mitochondrial dysfunction of normal aging and neurodegeneration

National Institute On Aging

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Abstract

Brain energy metabolism is crucial for normal cognitive function across the lifespan. Nicotinamide adenine dinucleotide (NAD+) is a central metabolite and signaling molecule which declines with age. Mitochondrial function also declines with increasing age, but how these two central metabolic processes influence one-another is not well understood. Using human samples, cell culture, C. elegans, and mouse models of normal and pathological aging, we will investigate the interrelationship between NAD+ metabolism and mitochondrial (dys)function across the lifespan. Using mouse models, we will perform analyses to determine if there is any relationship between NAD+ metabolism and mechanisms of mitochondrial bioenergetic dysfunction. These studies will inform future directions aimed at developing biomarkers for healthy and pathological aging.