Figure 3. Relationships between NAD⁺ and the Ten Hallmarks of Brain Aging.

The 10 hallmarks of brain aging include mitochondrial dysfunction; accumulation of oxidative damage; impaired waste disposal including autophagy, mitophagy, and proteostasis; Ca²⁺ deregulation; compromised adaptive stress responses; dysfunctional neuronal network; impaired DNA repair; inflammation; impaired neurogenesis; and senescence and telomere attrition. Evidence from cell culture, C. elegans, and mouse studies shows that NAD⁺ augmentation counteracts the adversities of the hallmarks of brain aging. See the text for details. iPSCs, induced pluripotent stem cells; NAD⁺, nicotinamide adenine dinucleotide; UPR^mt, mitochondrial unfolded protein response.