A vital “youth molecule” may help promoting quality of life in the older population – a conclusion from many clinical studies

Scientists from the University of Oslo (UiO), Akershus University Hospital (Ahus), and international partners have released a new expert opinion in Nature Aging. The article brings together more than 25 researchers from around the world, including clinicians and internationally recognised leaders in the biology of ageing and metabolism, particularly in the study of nicotinamide adenine dinucleotide (NAD⁺). Their collective perspective underscores the global effort to understand how this tiny molecule, NAD⁺, could be key to healthier ageing and protection against diseases such as Alzheimer’s and Parkinson’s.

NAD⁺ is often described as a cell’s “fuel regulator.” It helps our bodies produce energy, repair damaged DNA, and keep cells functioning properly. As we grow older, however, NAD⁺ levels naturally decline. This fall is linked to memory loss, muscle weakness, and many age-related diseases. “Fine-tuning NAD⁺ metabolism holds promise for delaying age-related health decline as well as disease such as premature ageing diseases” says Dr. Jianying Zhang, one of the lead authors. “But to truly unlock its potential, we need to better understand the right doses, long-term safety, and interindividual variability in response to NAD⁺ augmentation strategies.”

This study reviews years of research and clinical trials where scientists have tested ways to increase NAD⁺ levels, often by giving patients special vitamin-like compounds such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN). Early results are encouraging, with some trials reporting improvements in memory, movement, and metabolism. The researchers highlight that larger and longer-term clinician studies are needed to validate its clinical efficacies against different conditions.

A timely expert perspective

The Nature Aging article comes at a moment of intense scientific and public interests. Around the world, including in Norway, multiple clinical trials are under way testing NAD⁺ precursors such as NR and NMN. These supplements have also become part of a booming global commercial market, sparking debate about which compound is the most effective and whether the promising results seen in animal models will translate to patients.

“This is why we believe the timing is right to share an expert opinion,” says Dr. Evandro Fei Fang-Stavem, senior author and head of the Fang Lab at UiO and Ahus. “NAD⁺ is fundamental to life, yet there is still confusion and noise in the field about which supplements work best and how they should be used. Our article consolidates the evidence and provides a scientific roadmap to guide both ongoing research and future clinical use.”

Deputy Head of the Institute of Clinical Medicine, Prof. Torbjørn Omland, MD, PhD, MPH, and a co-author of the paper says, 'There is a knowledge gap on NAD⁺ and its clinical effects to basic researchers and clinicians, and this review paper provides the latest expert opinion to those who are interested in and are working in the field NAD⁺ research. This review will also provide relevant information to many NAD⁺-based clinical trials across a wide spectrum of clinical conditions, including neurological and cardiovascular disease'.

The authors emphasise that while NAD⁺ supplements and drugs are being widely studied, more collaboration and rigorous testing will be crucial to turn this exciting science into safe and effective treatments for ageing and age-related diseases.

Other Norwegian co-authors include Sofie Lautrup (UiO and Ahus), Hilde Loge Nilsen (OUS), Leiv Otto Watne (Ahus and UiO), Geir Selbæk (UiO and Norwegian National Centre for Ageing and Health), Mathias Ziegler (UiB), Ole-Bjørn Tysnes (UiB), Charalampos Tzoulis (UiB). Other main authors were from the University of Copenhagen (Denmark), Chiba University (Japan), Harvard Medical School (USA), and the Buck Institute for Research on Aging (USA).

Reference:
Zhang J, Wang H-L, Lautrup S, Nilsen HL, Treebak JT, Watne LO, Selbæk G, Wu LE, Omland T, Pirinen E, Cheung TC, Wang J, Ziegler M, Tysnes O-B, Zapata-Pérez R, Bruzzone S, Cantó C, Deleidi M, Janssens GE, Houtkooper RH, Scheibye-Knudsen M, Koshizaka M, Yokote K, Verdin E, Bohr VA, Tzoulis C, Sinclair DA & Fang EF. Emerging strategies, applications and challenges of targeting NAD⁺ in the clinic. Nature Aging (Published online 9 September 2025). DOI: 10.1038/s43587-025-00947-6.