Science 101

How Do We Know NAD+ Declines?

Human and animal studies both point to a decline in NAD+. Here’s the evidence from the study, “In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences.”

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The Takeaway:

Scientists know that NAD+ is one of the most important molecules in the body and that we lose it with age, resulting in variety of health issues. This study was the first to show that intracellular NAD+ levels in the human brain decline with age.

Aging is one of the hottest topics in science (not to mention the media) today, and for good reason: From large-scale studies on how lifestyle affects longevity to studies on the molecular and genetic causes of aging, researchers are getting closer than ever to understanding what actually causes aging and what can be done about it. It doesn’t hurt that the subject also captures the imagination of the public. Who doesn’t want to better understand why they age and do something to improve the odds of staying healthy for as long as possible?

In this study, published in Proceedings of the National Academy of Sciences, scientists at the University of Minnesota Center for Magnetic Resonance Research, Department of Radiology, were motivated to study NAD+ levels because previous research in animals linked a decline in NAD+ to age-related metabolic diseases and neurodegenerative disorders. Given their particular expertise, they were able to bring something brand new to the field of NAD+ research: a new way to measure intracellular NAD+ levels in the brains of living subjects.


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What They Studied:

Xiao-Hong Zhu and colleagues were interested in NAD+ levels because a wide body of research pointed to the importance of NAD+ in metabolism (specifically, in making energy) and because NAD+ regulates important cellular processes, “including calcium homeostasis, gene expression, aging, degeneration, and cell death.” If it’s so important, they reasoned, they needed a good way to measure it.

And that’s what they came up with: The scientists used an in vivo NAD+ assay — in vivo is the Latin phrase translating to “within the living” — which allowed them to measure intracellular NAD+ and NADH concentrations and the NAD+/NADH ratio in the human brain without removing any tissue from the participants. That’s useful for two reasons: removing a sample compromises the accuracy of the results of the experiment (it’s no longer “living”), and there are obvious challenges to removing samples of the human brain.

So how do you measure NAD+ levels in the brain without removing part of the brain? A unique method they developed using magnetic resonance, the same underlying technology used if you’ve ever had a sports injury and gone to the doctor for an MRI. Whereas a typical MRI scan looks at the different environments of hydrogen atoms, which are abundant in the body (in water, for example), the researchers in this study looked for phosphorus atoms instead. Because NAD+ contains phosphorus, it can be detected using this technique.

What They Discovered:

The study found that intracellular NAD+ levels and NAD redox potential — that’s the ratio of NAD+ to NADH, where a higher number is more favorable to creating energy and carrying out all the other processes requiring NAD+ — decline gradually but significantly with normal aging in healthy human brains.

What to Know Now:

The findings of this study in human brains are consistent with results of animal studies, which have also shown a decline in NAD+ in the brain with age. They’re also consistent with a large number of animal studies showing that NAD+ levels decline elsewhere in the organism, as well as another human study showing that NAD+ levels decline in skin with age. All of this matters because scientists consider the downward trend of NAD+ to be an important aspect of aging. It’s now possible to increase declining levels of NAD+ (for instance, with Basis) and NAD+ is and will increasingly be a target for researchers studying how to improve health in the aging population.

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