Raising the amount of nicotinamide adenine dinucleotide (NAD+) present in cells improves mitochondrial function in old tissues in which naturally maintained NAD+ levels have declined with aging. Mitochondrial function is important in cellular health, but falters with age for reasons that are complex, multifaceted, and poorly understood. Declining quality control mechanisms may be a large part of it, but even that is a many-layered set of changes, a fair way removed from the root cause molecular damage of aging. The NAD+ enhancement strategy, while not fixing the underlying causes of the issue, appears capable of modestly slowing aging in animal studies. A number of approaches and supplements can allegedly achieve this goal; the data to hand suggests that they vary widely in effectiveness, but there is at least human trial data for nicotinamide riboside.
An enzyme called eNAMPT is known to orchestrate a key step in the process cells use to make energy. With age, the body's cells become less and less efficient at producing this fuel - called NAD - which is required to keep the body healthy. Researchers have shown that supplementing eNAMPT in older mice with that of younger mice appears to be one route to boosting NAD fuel production and keeping aging at bay. Unlike other studies focused on transfusing whole blood from young mice to old mice, the researchers increased levels of a single blood component, eNAMPT, and showed its far-reaching effects, including improved insulin production, sleep quality, function of photoreceptors in the eye, and cognitive function in performance on memory tests, as well as increased running on a wheel.
The researchers have also shown other ways to boost NAD levels in tissues throughout the body. Most notably, the researchers have studied the effects of giving oral doses of a molecule called NMN, the chemical eNAMPT produces. NMN is being tested in human clinical trials. "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."
Research has shown that the hypothalamus is a major control center for aging throughout the body, and it is directed in large part 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 researchers have shown that the hypothalamus manufactures NAD using eNAMPT that makes its way to the brain through the bloodstream after being released from fat tissue. They also showed that this eNAMPT is carried in small particles called extracellular vesicles. As levels of eNAMPT in the blood decline, the hypothalamus loses its ability to function properly, decreasing life span.
Levels of eNAMPT in the blood were highly correlated with the number of days the mice lived. More eNAMPT meant a longer life span, and less meant a shorter one. The researchers also showed increased life span with delivering eNAMPT to normal old mice. All mice that received saline solution as a control had died before day 881, about 2.4 years. Of the mice that received eNAMPT, one is still alive as of this writing, surpassing 1,029 days, or about 2.8 years. "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."