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Scientists have identified NAD+ as a key molecule that helps protect brain health. However, NAD+ declines with age, and its depletion, particularly in the hippocampus -- the region of the brain responsible for memory -- has been linked to cognitive deficits.
In a new study published in the journal NPJ Aging, researchers at the University of Washington used a newly established method to accurately measure NAD+ levels in the hypothalamus of young and old mice. The study showed that NAD+ levels decreased significantly in three of the four subregions measured in the hypothalamus. Thus, a single injection of 300 mg/kg NMN into 22-month-old mice restored NAD+ levels in all three regions. In addition, the researchers found that injecting old mice with vesicles from young mice containing the NAD+ synthase NAMPT increased NAD+ levels in the hypothalamus by nearly 50 percent.
Before this study, scientists lacked techniques to accurately measure NAD+ levels in small tissues. Given that the hypothalamus is divided into extremely small subregions, called nuclei, there is little data on the role of NAD+ in hypothalamic aging. Using a new combination of NAD+ measurements, Imai and colleagues succeeded in showing that aged mice exhibit decreased NAD+ levels in three of the four measured subregions of the hypothalamus. In addition, preliminary findings confirm that NAD+ levels decrease in multiple brain regions, opening the door to future studies of the impact of reduced NAD+ in the hypothalamus.
Given that NMN is a potent NAD+ supplement in many tissues, the researchers examined whether injecting NMN into aged mice could rescue decreased hypothalamic NAD+ levels. Thirty minutes after the initial injection, aged mice exhibited increased levels of NAD in all four measured subregions of the hypothalamus. Furthermore, the findings showed that NMN attenuated the decline in NAD+ levels in the hypothalamus of aged mice.
NMN attenuated a decrease in NAD+ levels in four subregions of the hypothalamus. (Left) Aged mice (white) exhibit decreased NAD+ levels in the arcuate nucleus (ARC), ventromedial hypothalamus (VMH), and lateral hypothalamus (LH) of the hypothalamus compared with young mice (grey). (Right) NMN (white) increases NAD+ levels in all four hypothalamic subregions: ARC, VMH, LH, and dorsal hypothalamus (DMH).
NAMPT is a mature NAD+ enhancer in a variety of tissues and a longevity promoter, and previous studies have shown that transplantation of small vesicles from young mice can increase NAD+ and extend the lifespan of old mice. With this in mind, Imai and colleagues explored whether transplantation of similar vesicles could exert NAD+-boosting effects in the hypothalamus.
The findings showed that injecting aged mice with NAMPT-containing vesicles from young mice resulted in a significant increase in NAD+ levels in the hypothalamus. Given the findings that these vesicles have a strong NAD+ boost in the hypothalamus, it will be interesting to see whether this treatment attenuates age-related changes in the hypothalamus in sensory processing and emotion control.
NAMPT-containing vesicles increase hypothalamic NAD+ levels. Hypothalamic NAD was increased by approximately 50% in aged mice treated with NAMPT-containing vesicles from young mice (EVs) compared to untreated controls (CTRL).
*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.
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