USU Researchers Reveal How Single Molecule Unlocks Secrets of Aging

In a newly released study in the journal Nature Communications, by Utah State University researchers, Figure 1 features photos of two mice. They are both 10 months old, from the same litter, but they look very different. One has a dark, glossy coat, clear eyes and appears to be of a healthy weight. The other has a lighter, scruffy coat, cataracts, a hunched back, and looks frail — some of the hallmarks of old age we would recognize in humans. The mouse that appears older hasn’t aged through the passage of time, but because its body is running low on a single molecule.

Nicotinamide adenine dinucleotide, or NAD, is a molecule found in every cell in our bodies. It is made in the body from vitamin B3, also known as niacin, and has a role in helping cells regulate energy metabolism. It also contributes to cell signaling, inflammation regulation, DNA repair, and gene expression. NAD levels in the body decrease for several reasons, including vitamin B3 deficiency, disease, and chronological aging.

USU researchers, along with collaborators in the Chini Lab at the Mayo Clinic’s Kogod Center on Aging and at other institutions, authored the study in Nature Communications that reflects over six years of effort to understand what chronic NAD deficiency does across body systems. In doing so, they also note the ways in which the natural aging process and low NAD levels overlap in biological consequence.

Andres Benitez-Rosendo, a veterinarian and graduate student at Mayo Clinic, and Morgan Feuz, a 2026 Biomedical Sciences Ph.D. graduate from Utah State University’s Department of Veterinary Clinical and Life Sciences in the College of Veterinary Medicine, are shared first authors of the study, “Inducible chronic NAD deficiency in mice reveals multi-systemic phenotypical, metabolic, and transcriptional changes,”published Sept. 23.

By withholding vitamin B3 from the diets of acquired niacin dependency (ANDY) mice, which are genetically engineered to require dietary vitamin B3, as humans do, the researchers found that chronically low NAD levels led to decreased bone, lean, and fat mass, impaired exercise capacity, fur browning, a hunched back, frailty, cataracts, and shortened lifespan, in both male and female mice, as compared with ANDY mice on a diet that included vitamin B3.

“We learned some things that really shake the foundation of our understanding of what aging is,” said Ralph Meyer, who is one of the study’s senior authors and professor in USU’s College of Veterinary Medicine.

The findings help clarify which effects of aging may be related to low NAD levels. Conversely, “there are many aspects of aging that are not explained (by low NAD alone), which is also a really interesting finding,” Feuz said. “Aging is so multifaceted. One of our main findings is that low NAD itself is not all-encompassing, as far as aging goes, but there is a subset of overlap that could give us some important hypotheses moving forward for investigating different genes and mechanisms of age-related diseases in that shared window.”

Current USU doctoral candidate Laura Miller contributed to another key finding about NAD deficiency: some of its effects are reversible.

Working with USU’s MicroCT Facility and its Nikon XT H 225 ST 2x µCT scanner, Miller imaged bone samples from three groups of mice over the 21-week study. Mice that had low NAD levels typical of old age due to the experimental vitamin B3 deficiency showed bone resorption, which also happens in age-related osteoporosis in humans.

When vitamin B3 was added back into their food, ANDY mice with previously low NAD levels showed physical improvements across several body systems, including the partial recovery of bone structure, which is evident in Miller’s MicroCT scans.

This reversibility went beyond bones; the research documented how recovered levels of NAD corresponded with recoveries in some of the physical, metabolic, cellular, and gene-expression changes previously observed in the mice that had dietary vitamin B3 temporarily withheld.

Miller says learning to use the expensive and complex microCT scanner and 3D modeling software was a worthwhile challenge.

“It’s really interesting and we’ve gotten some cool data from it since,” she said, “looking at not only changes that occur in different tissues, but also, how do low NAD and old age impair bone strength and bone function?”

One practical application of this study, and a topic of future research, will be to help inform people considering NAD-boosting supplements for healthy aging, an industry that has already taken off despite lingering questions around safety and effectiveness.

“With this knowledge, following up on it, we can try to find better ways of staying healthy when you age,” said Mirella Meyer-Ficca, a lead and corresponding author of this paper and associate professor in the College of Veterinary Medicine. “The big question is not how can people live forever. The question is how can they live healthy and independent and happy. And if we understand what goes wrong during aging, we can try to prevent it.”

An award from USU’s Undergraduate Research and Creative Opportunity program helped fund the participation of Dr. Sierra Lopez, who contributed to the research as an undergraduate before entering the College of Veterinary Medicine and receiving her Doctor of Veterinary Medicine degree through USU’s partnership program with Washington State University.

Lexie Zwerdling also contributed to the research as a graduate student, and later as Meyer-Ficca’s lab manager, designing and conducting in vivo mouse experiments and sample collection while earning a Master’s degree in veterinary public health.

Ralph Meyer notes that most of USU’s research contribution reflected in this publication was done by students under supervision and guidance by Meyer-Ficca as part of their training.

“Learning by doing is what really trains a graduate student, and that training is what drives our research,” Meyer said. “We train them how to use instruments, in methods and techniques, and most importantly, how to approach a scientific problem. Students are front and center of this research; they did most of the hands-on work. We are proud of our students as they grow into the next generation of thinkers and problem solvers.”

Read the study: https://www.nature.com/articles/s41467-026-77996-x#article-info

• USU authors: Morgan B. Feuz, Sierra A. Lopez, Laura B. Miller, Alexie E. Zwerdling, Miles K. Wandersee, Ralph G. Meyer, Mirella L. Meyer-Ficca.
• Funding through the National Institutes of Health (AG069745); the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (HD100970 & HD103027); support from a Utah Agricultural Experiment Station grant, Utah State University (UTA01721) and support from a Utah State University Undergraduate Research and Creative Opportunity grant.