Interestingly, a recent study from the Bohr lab (Nat Commun, 2019 Nov 21;10(1):5284) showed that patients with WS model systems and patients had decreased levels of nicotinamide adenine dinucleotide (NAD⁺), 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 (NR) from Niagen Bioscience -- has shown promising results in animal studies, extending lifespan and protecting against age-related decline. In human clinical trials, NR has also demonstrated benefits against chronic inflammation, metabolic disorders, and muscle weakness across various populations. However, the effects of NR in WS 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 NR in patients with WS. 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 groundbreaking work involved a randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of NR supplementation. The research team enrolled patients with WS in a crossover design, where participants received either a daily dose of NR 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.

NR supplementation significantly increased NAD⁺ levels in patient blood compared to placebo. Importantly, NR improved arterial stiffness (a marker of cardiovascular disease risk), reduced the skin ulcer area, and appeared to slow the progression of kidney dysfunction -- all without any serious side effects. Moreover, a comprehensive examination of metabolites in blood revealed that NR treatment reduced levels of creatinine and other compounds associated with kidney dysfunction. This suggests that NR may help protect kidney function, addressing another serious complication of WS.

Dr. Yasmeen Nkrumah-Elie, Global Director of Niagen Bioscience's External Research Program called CERP, commented, "this study represents a significant step forward in understanding how NAD⁺ restoration with NR may help address the underlying biology of WS. By supporting cardiovascular, skin, and kidney health, NR shows potential to improve the quality of life for patients with this devastating condition. We are proud to support Chiba University's groundbreaking research as part of our ongoing commitment to advancing NAD⁺ science for rare and underserved diseases."

The treatment's multiple benefits across many different organ systems indicate that NAD⁺ depletion may be a fundamental mechanism in WS that can be targeted therapeutically. "Our findings suggest NR could serve as a valuable treatment option for two major symptoms, arteriosclerosis and skin ulcers, as well as for preventing kidney function decline," explains Dr. Koshizaka. The results are particularly significant given that untreatable skin ulcers affect well over 70% of patients with WS, often leading to amputation, while cardiovascular disease remains a leading cause of early mortality in this population.

Though larger studies are needed to extend these findings, this pioneering research offers new hope for patients with WS 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.

"We hope our work will accelerate studies on not only WS but also other premature aging disorders and common age-related diseases -- ultimately helping to extend health span and improve quality of life in both patients and the broader population," concludes Dr. Koshizaka.

There is a difference between arterial and venous blood clots. Blood clots in the arteries form when plaque in calcified vessels bursts and the body perceives it as an injury. This activates the platelets, which clump together and form a clot. In the worst case, it can lead to a stroke or heart attack. A venous thrombus, on the other hand, usually forms in the leg when the blood stagnates for too long. This can activate the body's coagulation system, allowing the clotting system to be activated and the blood to clot, blocking blood flow. If the clot breaks loose and travels with the blood to the lungs, it can lead to pulmonary embolism, a life-threatening condition.

"Venous thrombosis is in fact one of the most common causes of death in the world. It is a common disease that has always been somewhat overshadowed by arterial blood clots," says Bengt Zöller, a specialist in general medicine at Skåne University Hospital and professor of general medicine at Lund University.

In Sweden, more than 10,000 people suffer from venous thromboembolism each year and that number appears to be increasing. Several factors are contributing to this increase. One of the strongest risk factors is age, and as the number of older people in Sweden grows, the number of clots is also increasing. Ten per cent of 80-year-olds experience a blood clot at some point. The risk also increases if you are overweight or tall.

"The muscles control the blood flow in the veins and the legs become like columns of fluid where the force of gravity is strong. Too much sedentary and inactive behaviour, then, is harmful. Only the valves of the veins prevent backflow and if these are damaged, the risk of blood clots can increase. Therefore, tall people are more prone to blood clots, as their larger veins provide less blood flow, combined with the fact that blood must travel a greater distance back to the heart."

Because the heart pumps blood out into the arteries, there is much higher blood pressure in the arteries than in the veins, which can contribute to atherosclerosis. High blood pressure, high levels of blood lipids and smoking are all risk factors for atherosclerosis of the arteries. But because the veins are a low-pressure system, the vessels do not become atherosclerotic. Therefore, neither high blood pressure nor blood lipids are associated with venous clots and smoking is considered only a weak to moderate risk factor. Being overweight, on the other hand, is a very significant culprit. Obesity has a negative impact on venous circulation, especially when combined with the fact that overweight people are often less active. Some clotting factors are also affected by obesity.

"In terms of diet, there are fewer studies, but ultra-processed foods have been associated with a slightly increased risk of blood clots, and plant-based, healthy foods with a reduced risk. In our studies, we have also seen that commercial fishermen have a lower risk, which may be due to a higher omega-3 content in their diet."

There are also specific situations in which the risk of venous blood clots is particularly high. The risk of blood clots increases when blood flow is reduced, such as when travelling by air for long periods of time or when lying in bed for several days. Surgery or inflammation that damages the vessel wall can also lead to an increased tendency to clot. Particularly during pregnancy, blood clotting factors increase and levels of some protective proteins may decrease.

"In these risk situations, prophylaxis in the form of blood thinners may be particularly important if other risk factors are also present."

Other risk factors are the genetic variants that affect different parts of the blood's clotting ability. In Sweden, we have a high prevalence of APC (activated protein C) resistance due to an inherited mutation in the gene for coagulation factor V, called Factor V Leiden. About 10 per cent of Swedes have this mutation, which is considered the most common coagulation mutation among Indo-Europeans.

"Evolutionarily, bleeding less has been an advantage, but in our modern, sedentary society, APC resistance is becoming a risk factor."

Bengt Zöller and his fellow researchers have now identified the strongest genetic risk factor since Factor V Leiden was discovered. They used data from the population-based Malmö Kost Cancer study, involving 30,000 Malmö residents. By selecting 27 genes previously associated with clotting disorders, they found three variants that, when taken together, were as significant a risk factor for venous blood clots as Factor V Leiden: ABO, F8, and VWF each increased the risk of venous blood clots by 10 to 30 percent.

"And the more of these variants a person has - the higher the risk. An individual with five of these gene variants has a 180 per cent higher risk of venous thrombosis. Unlike Factor V Leiden, which is only found in Indo-Europeans, these three different mutations are found in between five and fifty per cent of various populations around the globe."

As these genetic variants are present in all populations, the next step is to investigate how the number of risk genes affects the duration of treatment with anticoagulants after a blood clot.

"I think tailoring treatment based on risk assessment will become increasingly important," concludes Bengt Zöller.

What you can do to prevent blood clots:

• Movement: Avoid sitting still for long periods. Stand up and move around on long flights.
• Support stockings: Can help blood flow when you must stand or sit for long periods.
• Blood-thinning medicines: Can be given prophylactically in high-risk situations such as surgery, cancer and others.
• Contraceptive pills containing oestrogen: avoid contraceptive pills containing oestrogen or hormone replacement therapy if there is strong heredity for venous thromboembolism or if you have a history of blood clots.
• Lifestyle changes: Stop smoking, eat healthier, lose weight and exercise.
• Get vaccinated: Infections can activate the coagulation system.

Blood clot

A blood clot consists of coagulated blood that has become lodged in a blood vessel. Clots can form either in the oxygen-rich blood in the body's arteries as it is pumped out of the heart, or in the low-oxygen blood in the veins (usually in the legs) as it is returned to the lungs and heart.

Their findings, published in JAMA Internal Medicine, also show that the profile of those who use cannabis has changed in recent years, with pronounced increases in use by older adults who are college-educated, married, female, and have higher incomes.

"Our study shows that cannabis use among older adults continues to increase, although there have been major shifts in use according to demographic and socioeconomic factors," said Joseph Palamar, PhD, MPH, an associate professor of population health at NYU Grossman School of Medicine, an affiliated researcher with CDUHR, and the study's senior author.

Most Americans live in a state where marijuana has been legalized for medical use, recreational use, or both. To better understand the prevalence of marijuana use among older adults in the US, researchers examined data from the National Survey on Drug Use and Health from 2021 through 2023. The respondents, who were 65 and older, were asked about past-month cannabis use, which was defined as "current" use.

"This is the first time we were able to examine 'current' use of cannabis in this age group. Before, we were only able to look at past-year use because the numbers for current use were too small," said Benjamin Han, MD, MPH, associate professor and associate chief of research in the Division of Geriatrics, Gerontology, and Palliative Care at the University of California San Diego and the study's first author.

The researchers found that current cannabis use among older adults grew to 7 percent in 2023, up from 4.8 percent in 2021 and 5.2 percent in 2022 -- a nearly 46 percent increase in only two years.

"If we look even further back to 2006 and 2007, less than 1 percent of older adults used cannabis in the past year. Now, we're seeing that 7 percent have used it in the past month alone," said Han, an affiliated researcher with CDUHR.

Certain groups of older adults experienced sharper increases in use over this period than others, including those who are married, white, have a college degree, and have an income of at least $75,000. Older women also saw a steep increase in cannabis use, although older men are still more likely than women to use the drug.

In addition, cannabis use grew more among those living in states where medical marijuana is legal versus states where it is not.

"It shouldn't be surprising that use is becoming increasingly more common among people who live in states that allow medical cannabis, which could be due to increased availability or social acceptability," said Palamar. "Interestingly, with respect to income, those with the highest incomes had the lowest prevalence of cannabis use in 2021, but by 2023 this group had the highest prevalence, which may indicate who has access to medical cannabis given its costs."

The researchers also found significant increases in cannabis use by older adults with chronic diseases -- and notably, those with multiple chronic conditions -- including heart issues, diabetes, hypertension, cancer, and chronic pulmonary obstructive disease.

The authors caution that the overall increases may be driven, in part, by those who use cannabis aging into the 65+ age bracket for the period studied. Regardless, they recommend that clinicians screen and educate their older patients about cannabis use, including how physiological changes that accompany aging can make people more sensitive to psychoactive substances.

"As a geriatrician, I see more and more people interested in using cannabis for treating chronic health symptoms. But cannabis can complicate the management of chronic diseases and be potentially harmful if patients are not educated on its use and potential risks," said Han.

Kevin H. Yang of UC San Diego and Charles Cleland of NYU Grossman School of Medicine were also co-authors on the study. The research was supported by the National Institute on Drug Abuse (K23DA043651, R21DA058404, R21DA060362, R01DA057289, R01DA060207, and P30DA01104) and the UC San Diego Sam and Rose Stein Institute for Research on Aging.