New research from Washington University School of Medicine in St. Louis is offering a novel hypothesis to possibly explain the long-standing idea that transfusions of young blood can help reverse the effects of aging. The study reveals when older mice are supplemented with a specific protein taken from the blood of younger mice, they live longer and exhibit more youthful characteristics.

The research focuses on a compound called nicotinamide adenine dinucleotide (NAD), which has become the focus of a great deal of anti-aging research over the last few years. Scientists have discovered NAD is essential for healthy energy metabolism, and its levels systematically decline in all tissues in the body as we age.

"We think the body has so many redundant systems to maintain proper NAD levels because it is so important," explains Shin-ichiro Imai, senior author on the new study. "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."

The new research homed in on a protein called eNAMPT, which circulates in the bloodstream and plays a fundamental role in the biosynthesis of NAD. While some earlier studies have discovered straightforward transfusions of blood from young mice to older mice can transfer youthful properties, it has been unclear exactly what mechanism could be underpinning this strange correlation. The new study suggests circulating eNAMPT may be the answer.

"We have found a totally new pathway toward healthy aging," says Imai. "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 study describes several mouse experiments that discovered these eNAMPT transfusions improve a number of age-associated traits in the older animals. As well as improving photoreceptor function in the eye and cognitive performance in memory tests, the eNAMPT supplementation extended the animals' lifespan by an average of 16 percent.

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

The researchers were also able to use circulating eNAMPT levels to effectively predict the overall lifespan of individual animals. The more eNAMPT found in the bloodstream, the longer the animal ultimately lived, suggesting this may be a useful aging biomarker in future studies.

Of course, all the usual caveats apply for research such as this, not the least being the fact that so far these results have only been verified in animal studies. While eNAMPT is found in human blood, more work is needed to establish whether supplementation confers these same beneficial properties in human subjects. It is relatively early days in the field of NAD research, but some initial human trials have been completed suggesting augmenting NAD either directly, or through the supply of NAD precursors, is potentially safe and physiologically beneficial.

Exactly how to best boost NAD levels in older humans is still yet to determined. Vitamin B3, or niacin, for example, is known to be a NAD precursor, however, it has been found to generate unwanted side effects when administered at high enough levels to effectively bump NAD levels up in the human body. The next stage for this current research is to look at whether eNAMPT supplementation is a safe way to enhance NAD levels in older humans.

The new research was published in the journal Cell Metabolism.