Werner syndrome (WES), a rare genetic disorder that causes accelerated aging. From their twenties, patients develop gray hair, hair loss, cataracts, diabetes, and other age-related conditions normally seen in the elderly. Additionally, patients develop severe and untreatable skin ulcers, often requiring limb amputation, and face early death from cardiovascular diseases or cancer. This debilitating condition lacks effective treatment options. In the first clinical trial of its kind, researchers from Japan with the company Niagen Bioscience, investigated the effects of nicotinamide riboside (NAR), a vitamin B3 derivative, in patients with WES. Interestingly, a recent study from the Bohr lab in 2019 showed that patients with WES model systems and patients had decreased levels of NAD+ cofactor, a biomolecule crucial for cellular energy production, DNA repair and various metabolic processes.
This finding suggested that NAD+ depletion may contribute to the progression of the disease. While direct NAD+ supplementation isn’t feasible in mammals, using its precursor nicotinamide riboside (NAR; from Niagen Bioscience) has shown promising results in animal studies, extending lifespan and protecting against age-related decline. In human clinical trials, NAR has also benefits against chronic inflammation, metabolic disorders and muscle weakness across various populations. However, the effects of NAR in WES remained largely unexplored, until now. In a recent study, a research team led by Associate Professor Masaya Koshizaka from the Center for Preventive Medical Sciences, Chiba University/Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan, conducted the world’s first rigorous clinical trial of NAR in patients with WES.
Their paper, published in Aging Cell on June 03, 2025, was co-authored by University President Koutaro Yokote, Assistant Professor Hisaya Kato, Associate Professor Yoshiro Maezawa, and Assistant Professor Mayumi Shoji, all from Chiba University, along with Affiliate Professor Vilhelm Bohr from the University of Copenhagen, Denmark. This investigation involved a randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of NAR supplementation. The research team enrolled patients with WES in a crossover design, where participants received either a daily dose of NAR or a placebo for 26 weeks, switched treatments for another 26 weeks. Researchers tracked NAD+ blood levels, skin ulcer size, arterial stiffness and kidney function. Importantly, NAR improved arterial stiffness, reduced the skin ulcer area, and appeared to slow the progression of kidney dysfunction—all without any serious side effects.
The treatment’s multiple benefits across many different organ systems indicate that NAD+ depletion may be a fundamental mechanism in WES that can be targeted therapeutically. The results are particularly significant given that untreatable skin ulcers affect well over 70% of patients with WES, often leading to amputation, while cardiovascular disease remains a leading cause of early mortality in this subjects. Though larger studies are needed to extend these findings, this pioneering research offers new hope for patients with WES who have long lacked effective treatment options. Beyond its immediate implications for this rare condition, the study also provides valuable insights into the biology of aging and potential interventions to address age-related decline more broadly.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Shoji M, Kato H et al. Aging Cell. 2025 Jun 3:e70093.
Aono K et al. Aging (Albany NY). 2024; 16(22):13526.
Maeda Y et al. Aging (Albany NY). 2023; 15(9):3273.
