New research in mice uncovers a previously unknown "pathway toward healthy aging." A circulating protein from the blood of young mice led to health improvements and visible signs of rejuvenation when researchers gave it to aging mice.

As well as hair loss, wrinkles, and lessening mobility, less visible, underlying bodily changes also characterize the aging process. One of these changes is the loss of a kind of "fuel" that keeps the body healthy—the so-called nicotinamide adenine dinucleotide (NAD).

NAD plays key roles in metabolism, DNA repair, and overall aging and longevity. With time, however, aging cells find it harder to produce energy, in general, and NAD, in particular.

But, in the energy-making process there is another critical player—an enzyme called eNAMPT. New research finds that taking eNAMPT from the blood of younger mice and giving it to older mice boosts NAD levels and staves off aging.

The findings appear in the journal Cell Metabolism. Dr. Shin-ichiro Imai, PhD, who is a professor of developmental biology at Washington University School of Medicine in St. Louis, MO, is the senior author of the study.

The role of NAD and eNAMPT in aging

Dr. Imai and colleagues revealed the beneficial effects of eNAMPT in previous research in mice. They showed that raised blood levels of this circulating protein improved insulin resistance, sleep quality, mobility, and cognitive function in older mice. "We think the body has so many redundant systems to maintain proper NAD levels because it is so important," says Dr. Imai.

"Our work and others' suggest it governs how long we live and how healthy we remain as we age. Since we know that NAD inevitably declines with age, whether in worms, fruit flies, mice, or people, many researchers are interested in finding anti-aging interventions that might maintain NAD levels as we get older."

Zooming in on the NAD-creating process, the researchers also showed that the hypothalamus—a brain region responsible for regulating metabolic processes, temperature, thirst, hunger, and sleep-wake cycles—produces NAD using the eNAMPT enzyme. The hypothalamus is also critical for the aging process.

eNAMPT lengthens lifespan by 16%

In their new research, Dr. Imai and team explain that eNAMPT travels through the bloodstream to the brain in small "carriers" called extracellular vesicles. This fact is true for both mice and humans.

They also reveal that blood levels of eNAMPT drop with aging, so less of it reaches the brain's hypothalamus. In turn, the hypothalamus stops working properly, shortening the life span.

In the Cell Metabolism paper, the scientists show that levels of eNAMPT were directly proportional to how long the mice lived.

The group of older mice that received eNAMPT lived at least 1,029 days, or 2.8 years, whereas the control group that they gave saline solution to survived only 881 days, or approximately 2.4 years. Overall, administering eNAMPT to older mice led to a lifespan increase of 16%.

"We were surprised by the dramatic differences between the old mice that received the eNAMPT of young mice and old mice that received saline as a control," Dr. Imai comments.

"These are old mice with no special genetic modifications, and when supplemented with eNAMPT, their wheel-running behavior, sleep patterns, and physical appearance—thicker, shinier fur, for example—resemble that of young mice."

—Dr. Shin-ichiro Imai

Meaning for humans of 'remarkable' results?

"We have found a totally new pathway toward healthy aging," Dr. Imai adds. "That we can take eNAMPT from the blood of young mice and give it to older mice and see that the older mice show marked improvements in health—including increased physical activity and better sleep—is remarkable."

The researchers say that future studies should examine if eNAMPT levels correlate with aging-related diseases or lifespan in humans. "We could predict, with surprising accuracy, how long mice would live based on their levels of circulating eNAMPT," says Dr. Imai.

"We don't know yet if this association is present in people, but it does suggest that eNAMPT levels should be studied further to see if it could be used as a potential biomarker of aging."