NMN Helps Keep the Brain’s Blood Supply Healthy, Even in Old Age

The origins of cognitive decline may be traced to deficiencies in how the brain’s blood supply is delivered to the neurons and other neural cells that comprise it. The brain demands a steady supply of power because of its importance in regulating different body functions, from breathing to heart rate, and its role in cognitive function, allowing us to experience life. As a result, it is completely dependent on the circulatory system’s ability to supply it with oxygen and nutrients.

As we get older, maintaining proper circulation to the brain becomes more challenging. The body’s ability to maintain and create new blood vessels is essential for maintaining a healthy microcirculatory network in the brain. Compromises in this network lead to loss of function and degeneration of the nervous system (neurodegeneration) (1-3). So, there is a demand for finding methods to maintain a healthy blood supply to the brain as we age.

Nicotinamide adenine dinucleotide levels are essential to brain function

Nicotinamide adenine dinucleotide, or NAD+, is a critical coenzyme found in all cells of the body that is essential for processing energy and is responsible for hundreds of metabolic processes. NAD+ plays an important role in the preservation of the network of small blood vessels that irrigate the brain. Aging is associated with a decline in NAD+, and researchers have noted that administration of NAD+ precursors, such as nicotinamide mononucleotide (NMN), preserve the circulatory infrastructure and help maintain blood vessel function.

NMN has been suggested as a viable way of preserving brain circulation by elevating NAD+ levels. Adequate levels of NAD+ not only preserve circulation in the brain, but are also necessary for energy production within neurons, maintaining adaptive stress responses, and normal activation of pro-survival anti-aging pathways. However, NAD+ becomes less available to cells as we age (4).

Previous research done in aged rodents has demonstrated the powerful anti-aging properties of NMN. These studies show that NMN helped preserve organ function in old rodents (5) and increased their lifespan (6). Also, NMN administration can restore vascular NAD+ levels and improve cerebral blood supply (7). Yet, it is unclear how exactly NMN is fortifying blood supply.

How does nicotinamide mononucleotide improve an aging brain’s blood supply?

A study recently published in the journal GeroScience sheds some light on how this process works (8). Kiss and colleagues from the University of Oklahoma Health Sciences Center set out to understand how the production of new blood vessels, known as angiogenesis, is affected by NMN. To do this, the researchers studied rat cerebro-microvascular endothelial cells — those that form the inner lining of blood vessels in the brain. They measured several key indicators for angiogenesis, or the ability to form new blood vessels: cell proliferation, migration, and capillary formation.

The control cells were observed as it went through a simulated aging process. After careful observation, results showed that their capacity for proliferation slowed significantly, compared to observations made in younger cells. However, after a brief period of exposure to NMN, the proliferation of these blood supplying cells returned to levels seen in the younger cells.

Since the migration of these endothelial cells plays a pivotal role in the maintenance of microvascular integrity and angiogenesis, Kiss and colleagues probed the migratory capabilities of cerebro-microvascular endothelial cells. To do this, they tested the ability of these cells to heal after being wounded. Just as with proliferation, the aged cells exhibited impaired migratory capabilities compared to the younger group. But yet again, older cells treated with NMN retained similar migratory capabilities as those observed in their younger counterparts.

Kiss and colleagues also measured the formation of very tiny blood vessels critical for new blood vessels called capillaries. These capillaries are the first step for producing tube-like structures that will mature into blood vessels. The researchers observed that the capacity of the endothelial cells to organize themselves into capillary structures declines with age. After treating the aged endothelial cells with NMN, the capillary organization was improved to similar levels as those seen in younger cells.

The study also showed the effect that NMN has in reversing blood vessel damage and circulatory dysfunction in the brain caused by oxidative stress, which is damaging to cells and the DNA inside of them. This is further evidence of the antioxidant capabilities of NMN and a clear indication that NMN can partially counteract some of the effects of aging.

The results from the study show that age-related decline in NAD+ affects the brain’s microcirculation because it impairs the capacity to heal and create new blood vessels. However, treatment with NMN has the capacity to restore NAD+ and thus preserve adequate irrigation to brain tissue.

Will NMN prevent cerebrovascular dysfunction in humans?

These results are very promising for future research into treatment for cerebrovascular events, such as strokes. The results show NMN’s potential for prevention and the preservation of the brain’s microcirculation. The authors conclude by recommending further research into NMN and by proposing studies to evaluate the effects of NMN in humans.

References:

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2.     Khan AS, Lynch CD, Sane DC, Willingham MC, Sonntag WE. Growth hormone increases regional coronary blood flow and capillary density in aged rats. J Gerontol A Biol Sci Med Sci. 2001;56(8):B364-B371. doi:10.1093/gerona/56.8.b364
3.     Warrington JP, Csiszar A, Mitschelen M, Lee YW, Sonntag WE. Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia. PLoS One. 2012;7(1):e30444. doi:10.1371/journal.pone.0030444
4.     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
5.     Johnson S, Wozniak DF, Imai S. CA1 Nampt knockdown recapitulates hippocampal cognitive phenotypes in old mice which nicotinamide mononucleotide improves. NPJ Aging Mech Dis. 2018;4:10. Published 2018 Nov 8. doi:10.1038/s41514-018-0029-z
6.     Zhang H, Ryu D, Wu Y, et al. NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-1443. doi:10.1126/science.aaf2693
7.     Tarantini S, Valcarcel-Ares MN, Toth P, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol. 2019;24:101192. doi:10.1016/j.redox.2019.101192
8.     Kiss T, Balasubramanian P, Valcarcel-Ares MN, et al. Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment. Geroscience. 2019;41(5):619-630. doi:10.1007/s11357-019-00074-2