Key Points:
- NR elevates NAD+ levels and reduces artery stiffening, an indicator of cardiovascular aging, in adults with Werner syndrome.
- Supplementing with NR improves markers of kidney health and elevates the longevity-associated molecule spermidine.
- The findings imply that NR may counteract accelerated aging in the general population.
For individuals with Werner syndrome, aging does not follow a normal timeline. With an average life expectancy of 55 years, this rare genetic disorder causes accelerated aging across multiple body systems, often leading to cardiovascular disease or cancer. However, a lack of treatment options has led scientists to search for non-pharmaceutical solutions.
In a new clinical trial published in the journal Aging Cell, scientists from Chiba University in Japan have found that NR supplementation improves cardiovascular health, reduces skin ulcers, and appears to protect kidney function in patients with Werner syndrome. The findings suggest that NR can serve as a valuable treatment option for cardiovascular, skin, and kidney aging.
The NAD+ Connection
The scientific basis for choosing NR as a potential treatment approach stems from a discovery made in 2019. Researchers found patients with Werner syndrome to have decreased levels of NAD+ in their skin cells. This is important because NAD+ serves as a critical component of cellular energy production, DNA repair, and metabolic regulation. While NAD+ levels naturally decline with age in all humans, this decline appears accelerated in Werner syndrome.
Thus, NAD+ depletion may contribute to the progression of Werner syndrome, but direct supplementation with NAD+ isn’t feasible because the molecule cannot efficiently enter cells when taken orally. However, precursor compounds that the body can convert into NAD+ solve this problem. NR is one such precursor that has shown promise in animal studies and other human clinical trials for increasing NAD+ levels.
NR Counteracts Accelerated Aging
To evaluate whether NR helps with accelerated aging, the Chiba University team conducted the world’s first clinical trial on Werner syndrome patients. Participants received either 1000 mg of NR or a placebo daily for 26 weeks, then switched to the opposite treatment for another 26 weeks. This crossover design enabled each participant to serve as their own control, thereby increasing the reliability of the results, despite having only nine participants, a necessity given the rarity of the condition.
The researchers tracked multiple health measures, including NAD+ levels in blood, skin ulcer size, arterial stiffness (a predictor of cardiovascular risk), and various indicators of kidney function. The treatment successfully increased NAD+ levels in patients’ blood compared to placebo, confirming that the supplement was working as intended. Moreover, NR improved arterial stiffness, as measured by the cardio-ankle vascular index (CAVI). Stiffer arteries increase the risk of heart attacks and strokes, so this improvement could potentially reduce the cardiovascular complications.
Furthermore, metabolomic analysis revealed that NR treatment reduced levels of creatinine and other compounds associated with kidney dysfunction, suggesting it may help protect against kidney aging. The treatment also reduced the area of skin ulcers, a particularly meaningful finding given that these painful, difficult-to-treat wounds affect many Werner syndrome patients and often lead to limb amputation.
Notably, NR was shown to elevate concentrations of spermidine, a molecule associated with health and longevity. Overall, by supporting cardiovascular, skin, and kidney health, NR shows the potential to improve the quality of life for Werner syndrome patients and beyond.
Implications for Normative Aging
While the study focused specifically on Werner syndrome, its findings may have broader implications for aging. Werner syndrome is often studied as a model of accelerated aging, and insights gained from this rare condition could potentially inform our understanding of normal aging processes. The multi-system benefits observed with NR supplementation support the idea that NAD+ decline may be a fundamental mechanism in aging that can be therapeutically targeted.
With that said, research is moving away from the disease-by-disease approach to aging and toward targeting fundamental aging mechanisms that contribute to multiple conditions, including cellular senescence, chronic inflammation, and mitochondrial dysfunction. This integrated approach recognizes that many age-related diseases share common underlying mechanisms. Rather than developing separate treatments for heart disease, diabetes, kidney disease, and other conditions that become more common with age, researchers are exploring interventions that address the biological processes driving all of these conditions.
For the average person concerned about healthy aging, this research offers both promise and perspective. While NAD+ precursors like NR are commercially available as supplements, the evidence for their benefits in healthy aging adults remains preliminary. The most robust evidence still supports established approaches to healthy aging: regular physical activity, a balanced diet rich in plant foods, adequate sleep, stress management, and social connection.
Nevertheless, the Werner syndrome study adds to a growing body of evidence suggesting that certain aspects of aging may be more modifiable than previously thought. As this field advances, it may eventually lead to evidence-based interventions that help more people maintain health and function into later life. The goal is not necessarily to extend lifespan dramatically, but to extend ‘healthspan’—the period of life spent in good health. If insights from Werner syndrome research can help achieve that for the broader population, that would be a tremendous success.
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