Scientists are seeking new ways to extend healthy lifespans because we all want to live as long as we can in good health! Among these are a group of researchers at Washington University School of Medicine in St. Louis who have come one step closer to finding a way. Their new study in mice suggests a novel strategy that involves supplementing older mice with an enzyme (protein) called eNAMPT from younger mice. It has shown to successfully extend lifespans in the older mice. The study was published in the journal Cell Metabolism.
Here’s a video that shows two mice of the same age. The active mouse was given the enzyme; the less active mouse was given saline.
To sum it up, what they found is that there is a protein abundant in the blood of young mice which keeps them healthy. As the mice age, the levels of this protein decline bringing about health problems such as insulin resistance, weight gain, cognitive decline, and vision loss increase. (The same goes for all animals including humans.) When the researchers supplemented older mice with the protein obtained from younger mice, the decline in health was prolonged and it extended their lifespan by about 16%.
NAD, Fuel For Longevity
This new research focuses on a compound called nicotinamide adenine dinucleotide (NAD, also known as NAD+). Over the past few years, scientists have focused a lot on this compound in anti-aging research. It has led them to discover that NAD is essential for healthy energy metabolism, and its levels systematically decline in all tissues in the body as we age.
Shin-ichiro Imai, senior author on the new study, explains:
We think the body has so many redundant systems to maintain proper NAD levels because it is so important. 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.
So what they had to find out was how to keep NAD levels high. That’s where the protein called eNAMPT comes in; eNAMPT is an enzyme which circulates in the bloodstream and plays a fundamental role in the biosynthesis of NAD. NAD is essentially fuel and eNAMPT is responsible for orchestrating a key step in the process cells use to make that fuel (energy). With age, the body’s cells become less and less efficient at producing NAD. By supplementing the mice with eNAMPT, the researchers were able to boost NAD fuel production and keep aging at bay.
Imai said:
We have found a totally new pathway toward healthy aging. 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.
Testing
Several mouse experiments provided the same results: eNAMPT transfusions improve a number of age-associated traits in the older animals. It even improved photoreceptor function in the eye and cognitive performance in memory tests, in addition to extending their lifespan by 16%. All mice that received saline solution as a control had died before day 881, about 2.4 years, while of the mice that received eNAMPT, one is still alive surpassing 1,029 days, or about 2.8 years. The study also found that female mice showed consistently higher levels of the enzyme.
Imai said:
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. 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 Hypothalamus
The body’s major control center for aging is the hypothalamus. It is directed primarily by eNAMPT, which is released into the blood from fat tissue. The hypothalamus governs vital processes such as body temperature, thirst, sleep, circadian rhythms, and hormone levels. The hypothalamus manufactures NAD using eNAMPT that makes its way to the brain through the bloodstream after being released from fat tissue. This eNAMPT is carried through the bloodstream to and from the hypothalamus in small particles called extracellular vesicles. When levels of eNAMPT in the blood begin to decline, the hypothalamus loses its ability to function properly resulting in the decreasing lifespan.
Lifespan Prediction
The levels of circulating eNAMPT are a gage to lifespan. The researchers were able to predict how long an individual animal would live by the amount of eNAMPT found in the bloodstream. The more the animal had, the longer it would ultimately live. Therefore, eNAMPT may even be a useful aging biomarker in future studies.
Imai said:
We could predict, with surprising accuracy, how long mice would live based on their levels of circulating eNAMPT. 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.
Human Trials
Imai and his colleagues noted that eNAMPT also is carried in extracellular vesicles in humans. However, as of yet, they have only conducted studies on mice with the enzyme. The next stage for this current research is to investigate whether eNAMPT supplementation is a safe way to enhance NAD levels in older humans.
