Effect of Exercise and Oral Niacinamide Mononucleotide on Improving Mitochondrial Autophagy in Alzheimer’s Disease

Oral niacinamide mononucleotide (NMN) and aerobic exercise have been shown to enhance niacinamide adenine dinucleotide (NAD(+)) in the body. NAD(+) plays a critical role in the body and can directly and indirectly affect many key cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cell aging, and immune cell function. It is noteworthy that the level of NAD(+) decreases gradually with increasing age. Decreased levels of NAD(+) have been causally associated with a number of diseases associated with aging, including cognitive decline, cancer, metabolic diseases, sarcopenia, and frailty. Many diseases related to aging can be slowed down or even reversed by restoring NAD(+) levels. For example, oral NMN or exercise to increase NAD(+) levels in APP/PS1 mice have been proven to improve mitochondrial autophagy, but currently, there is no regimen combining oral NMN with exercise. This review summarizes recent studies on the effect of oral NMN on the enhancement of NAD(+) in vivo and the improvements in mitochondrial autophagy abnormalities in AD through aerobic exercise, focusing on (1) how oral NMN improves the internal NAD(+) level; (2) how exercise regulates the content of NAD(+) in the body; (3) the relationship between exercise activation of NAD(+) and AMPK; (4) how SIRT1 is regulated by NAD(+) and AMPK and activates PGC-1α to mediate mitochondrial autophagy through changes in mitochondrial dynamics. By summarizing the results of the above four aspects, and combined with the synthesis of NAD(+) in vivo, we can infer how exercise elevates the level of NAD(+) in vivo to mediate mitochondrial autophagy, so as to propose a new hypothesis that exercise interferes with Alzheimer’s disease (AD).