NMN may supplement NAD+ levels in aging brain

In a new study published in the journal NPJ Aging, UW researchers used a new method to accurately measure NAD+ levels in the hypothalamus of young and old mice[1].

Imai and colleagues found that NAD+ levels decreased significantly in three of four measured subregions of the hypothalamus.

Correspondingly, a single dose of 300 mg/kg NMN injected into 22-month-old mice restored NAD+ levels in all three regions.

In addition, the researchers found that injecting aged mice with vesicles containing the NAD+ synthase NAMPT increased NAD+ levels in the hypothalamus by nearly 50 percent.

NMN restores decreased NAD+ levels in hypothalamus

Before this study, scientists lacked the technology to accurately measure NAD+ levels in small tissues.

Because the hypothalamus is divided into extremely small subregions called nuclei, data on the role of NAD+ in hypothalamic aging are very limited.

Using a new combinatorial approach to NAD+ measurements, Imai and colleagues succeeded in showing that NAD+ levels decreased in aged mice in three of the four measured subregions of the hypothalamus.

NAMPT-containing vesicles increase hypothalamic NAD+ levels

NAMPT is an NAD+ enhancer and longevity promoter in multiple tissues, and previous studies have shown that transplantation of small vesicles from young mice boosts NAD+ and extends lifespan in older mice.

With this in mind, Imai and colleagues investigated whether transplantation of similar vesicles could exert NAD+ enhancing effects in the hypothalamus.

NMN and eNAMPT as potential therapeutic interventions in brain aging

As Imai and colleagues establish a new model to accurately quantify hypothalamic NAD+ levels, we can better monitor hypothalamic aging and potentially identify new therapeutic approaches.

Our brains inevitably experience age-related declines in function from ongoing damage from continuous stressors such as inflammation and DNA damage, which rely on NAD+ for mitigation.

Therefore, finding ways to replenish NAD+ in multiple tissues is critical to inhibit aging and organ degeneration.

The current findings show that NMN and eNAMPT successfully restore NAD+ levels in the aged hypothalamus, highlighting the potential for these treatments to improve aspects of brain aging such as poorer sleep quality, decreased physical function, and impaired cognition.

[1] Johnson, S., Yoshioka, K., Brace, C.S. et al. Quantification of localized NAD+ changes reveals unique specificity of NAD+ regulation in the hypothalamus. npj Aging 9, 1 (2023).

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