Published: 4:27 p.m. PST Apr 7, 2020 | Updated: 4:45 p.m. PST Oct 6, 2020
Imagine during your older years walking out to your car and realizing you forgot your car keys. Lapses in memory like this can result from miscommunication and dysfunction of neurons and blood vessels of the brain, which constitute what neuroscientists call the neurovascular unit. This blood-supplying apparatus functions to distribute nutrients to neurons. However, the malfunction of the neurovascular unit over the course of years leads to brain degenerating conditions like Alzheimer’s and cognitive impairment.
A research team from the University of Oklahoma published a study in GeroScience finding that nicotinamide mononucleotide (NMN) supplementation reversed the effects of aging on the neurovascular units and restored cellular pathways. This suggests that NMN supplementation may combat age-related deterioration caused by neurovascular unit dysfunction.
NMN is a precursor to a molecule nicotinamide adenine dinucleotide (NAD+), which plays crucial roles in lifespan regulation, metabolism, and cellular health. With age, NAD+ levels decline, resulting in, amongst many things, the reduced activation of proteins dependent on NAD+ like sirtuins. These NAD+-dependent enzymes maintain DNA and chromosomal health and help with cellular health maintenance.
Kiss and colleagues examined the gene activity profiles of older mice injected with NMN. The University of Oklahoma observed that about 55% of the genes returned to youthful activity levels in aged mice following NMN treatment, indicating that NMN reverses aging-related changes in the neurovascular unit’s gene activity.
(Kiss et al., 2020) Neurovascular unit gene activity measurements in young mice, aged mice, and aged mice with NMN treatment. Genes with changed activity in aging are labeled blue, genes with changed activity levels with NMN treatment are labeled green, and genes with activity that shifted toward a more youthful expression profile are labeled red and grey.
Kiss and colleagues saw age-related changes in the activity of sirtuin-regulated genes, which were reversed with NMN treatment. More specifically, they found that genes sensitive to one particular sirtuin called SIRT were dysregulated in aged mice, but NMN treatment reversed these effects.
Besides providing protection through SIRT1, the study also showed that NMN rejuvenated the cell’s energy-generating powerhouse, the mitochondria, in aged mice. The activity of mitochondria-related genes in young and older mice treated with NMN were similar, suggesting that NMN treatment reversed the age-related dysregulation of mitochondria in the neurovascular unit.
In previous studies, NMN treatment increased blood flow and improved cognitive performance. The new genetics data compiled in the current study indicated NMN reverses age-related cellular changes in the neurovascular unit, notably changing gene activity associated with sirtuins and mitochondrial function. The scientist proposed that these results add to findings from earlier studies showing treatment with NMN provides anti-aging neurovascular changes in aged mice that reverse neurovascular unit dysfunction.
“Additional studies are warranted to determine the efficacy of combination treatments with NAD+ boosters and compounds that directly activate SIRT1 and/or inhibit NAD+ overutilization for neurovascular protection,” stated Kiss and colleagues.
The University of Oklahoma researchers noted using NMN in conjunction with molecules such as resveratrol that has demonstrated to exert protective effects on blood vessels in animals could potentially enhance these beneficial effects on neurovascular unit function. The method may serve as a possible intervention for patients who experience cognitive impairment from neurovascular dysfunction in the future.
Sweeney MD, Montagne A, Sagare AP, et al. Vascular dysfunction-The disregarded partner of Alzheimer’s disease. Alzheimers Dement. 2019;15(1):158-167. doi:10.1016/j.jalz.2018.07.222
Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018;27(3):513-528. doi:10.1016/j.cmet.2017.11.002