Continued Interest in Nicotinamide Mononucleotide

In the aging research community as it stands today there is much more work on approaches that can at best produce only small effects on the course of aging than there is work on approaches capable of rejuvenation and large gains in life span. The present growth of interest in supplementation with nicotinamide mononucleotide (NMN) falls into the former camp, shown to modestly slow aging in animal studies. We know that effects on aging in short-lived species are much larger than they are in humans, where there is the data to make direct comparisons of the same method or genetic alteration. The life spans of short-lived species are much more plastic in response to circumstances. Investigations of NMN, like the sirtuin research that led to it, cannot possibly produce large gains in human health. It is somewhat frustrating to see significant time and effort once again be directed towards a line of research in which the potential outcomes are so very limited, analogous to those produced by exercising a little more and eating a little less. Yes, it is more evidence for the importance of mitochondrial function in aging, but in a rational world that should be taken as nothing more than a sign that the research and development communities should put more effort into mitochondrial repair strategies, or the backup approach of allotopic expression so as to completely fix the problem in older individuals, not just slightly slow it down.

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency in the body's energy supply chain is a key driver of the aging process. Now, scientists have shown that supplementing healthy mice with a natural compound called NMN can compensate for this loss of energy production, reducing typical signs of aging such as gradual weight gain, loss of insulin sensitivity and declines in physical activity. "This means older mice have metabolism and energy levels resembling that of younger mice. Since human cells rely on this same energy production process, we are hopeful this will translate into a method to help people remain healthier as they age."

With age, the body loses its capacity to make a key element of energy production called NAD (nicotinamide adenine dinucleotide). Past work has shown that NAD levels decrease in multiple tissues as mice age. Past research also has shown that NAD is not effective when given directly to mice so the researchers sought an indirect method to boost its levels. To do so, they only had to look one step earlier in the NAD supply chain to a compound called NMN (nicotinamide mononucleotide). The new study shows that when NMN is dissolved in drinking water and given to mice, it appears in the bloodstream in less than three minutes. Importantly, the researchers also found that NMN in the blood is quickly converted to NAD in multiple tissues.

To determine the long-term effects of giving NMN, researchers studied three groups of healthy male mice fed regular mouse chow diets. Starting at five months of age, one group received a high dose of NMN-supplemented drinking water, another group received a low dose of the NMN drinking water, and a third group served as a control, receiving no NMN. The researchers compared multiple aspects of physiology between the groups, first at 5 months of age and then every three months, until the mice reached 17 months of age. Typical laboratory mice live about two years. The researchers found a variety of beneficial effects of NMN supplementation, including in skeletal muscle, liver function, bone density, eye function, insulin sensitivity, immune function, body weight and physical activity levels. But these benefits were seen exclusively in older mice. "When we give NMN to the young mice, they do not become healthier young mice. NMN supplementation has no effect in the young mice because they are still making plenty of their own NMN. We suspect that the increase in inflammation that happens with aging reduces the body's ability to make NMN and, by extension, NAD."

In skeletal muscle, the investigators found that NMN administration helps energy metabolism by improving the function of mitochondria, which operate as cellular power plants. They also found that mice given NMN gained less weight with aging even as they consumed more food, likely because their boosted metabolism generated more energy for physical activity. The researchers also found better function of the mouse retina with NMN supplementation, as well as increased tear production, which is often lost with aging. They also found improved insulin sensitivity in the older mice receiving NMN, and this difference remained significant even when they corrected for differences in body weight.


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