CAN NMN INCREASE LONGEVITY?

The first long-term lifespan study in mice involving supplementation with NMN, a precursor of NAD+ metabolism, which has been shown to reduce aging markers and increase sirtuin activity. We propose to conduct a longevity study using NMN in the drinking water of wild-type mice. We also propose to test NMN on a novel model of accelerated aging mice known as ICE mice (Induced Changes In Epigenome).

BY DR. DAVID A. SINCLAIR

One of the best studied anti-aging treatments is a diet reduced in calories, yet high enough in nutrients to avoid malnutrition. Known as calorie restriction (CR), this dietary regimen provides irrefutable evidence of the importance of metabolism in the aging process. While CR has been studied extensively and even tested in human trials, long term adherence to a CR dietary regimen is extremely difficult for most individuals to maintain.

One method to achieve the benefits of CR for everyone would be to administer compounds which act as “CR mimetics” . Such compounds are capable of inducing similar cellular changes that are normally seen during CR. Over the past 20 years, we have made great strides in understanding the key cellular components involved in mediating many of the metabolic changes that contribute to the aging process.

A major metabolic signaling molecule that we and others have shown to exhibit significant declines with increasing age is NAD+ . Importantly, CR reverses the age-related decline of bioavailable NAD+. This key metabolite plays a crucial role in regulating the activity of many important signaling molecules involved in age-related diseases.

However, feeding or administering NAD+ directly to organisms is not a practical option. The NAD+ molecule cannot readily cross cell membranes to enter cells, and therefore would be unavailable to positively affect metabolism. Instead, precursor molecules to NAD+ must be used to increase bioavailable levels of NAD+.

One such metabolic precursor of NAD+, niacin, is currently used as a medical therapeutic in humans to regulate blood lipid profiles and ward off cardiovascular disease. Niacin, however, is separated by many metabolic steps upstream of the final production of cellular NAD+, and thus has a limited impact on the magnitude of NAD+ bioavailability.

Recently, we have shown that by administering the NAD+ precursor NMN (Nicotinamide Mononucleotide)   in normal drinking water to older mice, NAD+ levels were restored to those normally associated with younger healthy animals. By administering NMN to mice for just one week, our lab demonstrated a robust correction in age-associated metabolic dysfunction and restored muscle mitochondrial function in old mice to levels seen in younger control mice .

Our group also administered NMN to advanced aged mice and saw improved DNA repair capacities in response to extrinsic stress and aging . This was followed up by our most recent study which demonstrated increased exercise endurance by improved blood vessel growth and increased blood flow in aged mice taking NMN