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The Gary Null Show – 03.31.21

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High-fiber diet may play a role in controlling the inflammation associated with COVID-19

In vitro treatment of cells with these molecules reduced the expression of a gene that plays a key role in viral cell entry and a cytokine receptor.

University of Campinas (Brazil), March 30, 2021

A study conducted at the University of Campinas (UNICAMP) in the state of São Paulo, Brazil, shows that compounds produced by gut microbiota (bacteria and other microorganisms) during fermentation of insoluble fiber from dietary plant matter do not affect the ability of the novel coronavirus SARS-CoV-2 to enter and replicate in cells lining the intestines. However, while in vitro treatment of cells with these molecules did not significantly influence local tissue infection, it reduced the expression of a gene that plays a key role in viral cell entry and a cytokine receptor that favors inflammation.

An article reporting the findings is published in the journal Gut Microbes.

Up to 50% of COVID-19 patients experience gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Such symptoms are detected in 17.6% of severe cases. They are partly associated with viral entry into intestinal cells resulting in alterations to their normal functions. In addition, recent studies point to major changes in patients’ gut microbiota, including a decrease in levels of bacteria that secrete short-chain fatty acids (SCFAs) by fermenting dietary fiber. SCFAs are important to colon health and maintenance of intestinal barrier integrity.

The researchers decided to confirm whether SFCAs directly affected the infection of intestinal cells by SARS-CoV-2. Previous studies had suggested alterations in gut microbiota and its products could modify an infected subject’s immune response.

“In earlier research, we found in animals that compounds produced by gut microbiota help protect the organism against respiratory infection. The model used there was respiratory syncytial virus [RSV], which causes bronchiolitis [inflammation of the small airways in the lung] and frequently infects children. Similar results have been obtained by other research groups in studies of different respiratory diseases,” said Patrícia Brito Rodrigues, who has a doctoral scholarship from FAPESP and is joint first author of the article with postdoctoral fellow Livia Bitencourt Pascoal. Rodrigues conducted the research as part of her doctorate at UNICAMP’s Institute of Biology (IB) with a scholarship from FAPESP.

In the latest study, healthy colon tissue and epithelial cells were infected with SARS-CoV-2 in the laboratory and subjected to a battery of tests.

“Viral load wasn’t reduced and was the same in cells and tissue treated with SCFAs and in untreated samples. However, treated intestinal biopsy samples displayed a significant decrease in expression of the gene DDX58 [an innate immune system receptor that detects viral nucleic acids and activates a signaling cascade that results in production of pro-inflammatory cytokines] and the interferon-lambda receptor, which mediates anti-viral activity. There was also a decrease in expression of the protein TMPRSS2, which is important to viral cell entry,” said Raquel Franco Leal, a professor at UNICAMP’s School of Medical Sciences (FCM), supported by FAPESP and co-principal investigator for the study with Marco Aurélio Ramirez Vinolo, a professor at IB-UNICAMP, also supported by FAPESP.

Protection against inflammation

The researchers took colon tissue samples from 11 patients without COVID-19. They also tested epithelial cells that line the intestines and are in close contact with gut microbiota. Tissue and cell samples were infected with SARS-CoV-2 in IB-UNICAMP’s Laboratory of Emerging Virus Studies (LEVE), a Biosafety Level III (BSL-3) facility led by José Luiz Proença Módena, a professor at IB-UNICAMP and a co-author of the article.

The tissues and cells were treated with a mixture of acetate, propionate and butyrate, compounds produced by gut microbiota metabolization of SCFAs present in dietary fiber. The treatment did not alter viral load in colon biopsies or cells, nor were there any changes in cell wall permeability and integrity.

“That doesn’t exclude the possibility of significant action by SCFAs on infection by SARS-CoV-2. The anti-viral effects could depend on interaction with other cells in the organism,” Rodrigues said. “We’ll continue our investigation in animal models since the action of these compounds on the infection could depend on a more complete system than the samples we used in vitro [isolated cells and tissues].”

Other tests involving non-treated infected biopsy samples showed an increase in expression of the gene DDX58, which encodes an important viral receptor, and of interferon-beta (IFN-beta), a pro-inflammatory molecule that participates in the cytokine storm associated with severe cases of COVID-19.

“Alterations in genes associated with virus recognition and response during intestinal infection may be relevant to the onset of the inflammatory chain,” Leal said. “In this context, it will be important to deepen the analysis of the effects of SCFAs with these parameters, as this could be significant in severe stages of the disease.”

Glycine-NAC combo improves multiple defects in aging to boost strength and cognition in older humans

Baylor School of Medicine, March 29, 2021

A pilot human clinical trial conducted by researchers at Baylor College of Medicine reveals that supplementation with GlyNAC—a combination of glycine and N-acetylcysteine as precursors of the natural antioxidant glutathione—could improve many age-associated defects in older humans to improve muscle strength and cognition, and promote healthy aging.

Published in the journal Clinical and Translational Medicine, the results of this study show that older humans taking GlyNAC for 24 weeks saw improvements in many characteristic defects of aging, including glutathione deficiency, oxidative stressmitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, body fat, genomic toxicity, muscle strength, gait speed, exercise capacity and cognitive function. The benefits declined after stopping supplementation for 12 weeks. GlyNAC supplementation was well tolerated during the study period.

“There is limited understanding as to why these defects occur in older humans, and effective interventions to reverse these defects are currently limited or lacking,” said corresponding author endocrinologist Dr. Rajagopal Sekhar, associate professor of medicine in the Section of Endocrinology, Diabetes and Metabolism at Baylor.

For the last 20 years, Sekhar and his team have been studying natural aging in older humans and aged mice. Their work brings mitochondria, known as the batteries of the cell, as well as free radicals and glutathione to the table in discussions about why we age.

Mitochondrial dysfunction and aging

Mitochondria generate energy needed for supporting cellular functions by burning fat and sugar from foods, therefore mitochondrial health is critically important for life. Sekhar believes that improving the health of malfunctioning mitochondria in aging is the key.

As mitochondria generate energy, they produce waste products such as free radicals. These highly reactive molecules can damage cells, membranes, lipids, proteins and DNA. Cells depend on antioxidants, such as glutathione, the most abundant antioxidant in our cells, to neutralize these toxic free radicals. Failing to neutralize free radicals leads to harmful and damaging oxidative stress that can affect mitochondrial function.

Interestingly, glutathione levels in older people are much lower than those in younger people, and the levels of oxidative stress are much higher.

Animal studies conducted in the Sekhar lab have shown that restoring glutathione levels by providing GlyNAC reverses glutathione deficiency, reduces oxidative stress and fully restores mitochondrial function in aged mice.

“In previous work we showed that supplementing HIV patients with GlyNAC improved multiple deficits associated with premature aging observed in those patients,” Sekhar said. “In this study, we wanted to understand the effects of GlyNAC supplementation on many age-associated defects in older adults.”

GlyNAC improves several hallmark defects in aging

The world population of older humans is rapidly increasing and with it comes an increase in many age-related illnesses. To understand what causes unhealthy aging, scientific research has identified nine hallmark defects which are believed to contribute to the aging process.

“It is believed that correcting these aging hallmarks could improve or reverse many age-related disorders and help people age in a healthier way,” Sekhar said. “However, we do not fully understand why these hallmark defects happen, and there are currently no solutions to fix even a single hallmark defect in aging.”

This is where Sekhar’s trial results become encouraging, because GlyNAC supplementation for 24 weeks appears to improve four of the nine aging hallmark defects.

To further understand whether GlyNAC holds the keys to mitochondrial recovery and more, Sekhar and his team conducted this pilot clinical trial.

“We worked with eight older adults 70 to 80 years of age, comparing them with gender-matched younger adults between 21 and 30 years old,” Sekhar said. “We measured glutathione in red-blood cells, mitochondrial fuel-oxidation, plasma biomarkers of oxidative stress and oxidant damage, inflammation, endothelial function, glucose and insulin, gait-speed, muscle strength, exercise capacity, cognitive tests, gene-damage, glucose-production and muscle-protein breakdown rates and body composition. Before taking GlyNAC, all these measurements were abnormal in older adults when compared with those in younger people.”

The older participants took GlyNAC for 24 weeks, and then stopped it for 12 weeks. Sekhar and his colleagues repeated the above measurements at the halfway point at 12 weeks, after 24 weeks of taking GlyNAC, and again after stopping GlyNAC for 12 weeks.

“We are very excited by the results,” Sekhar said. “After taking GlyNAC for 24 weeks, all these defects in older adults improved and some reversed to the levels found in young adults.” The researchers also determined that older adults tolerated GlyNAC well for 24 weeks. The benefits, however, declined after stopping GlyNAC supplementation for 12 weeks.

“I am particularly encouraged by the improvements in cognition and muscle strength,” Sekhar said. “Alzheimer’s disease and mild cognitive impairment (MCI) are serious medical conditions affecting memory in older people and leading to dementia, and there are no effective solutions for these disorders. We are exploring the possibility that GlyNAC could help with these conditions by conducting two pilot randomized clinical trials to test whether GlyNAC supplementation could improve defects linked to cognitive decline in Alzheimer’s disease and in MCI, and possibly improve cognitive function.”

“The overall findings of the current study are highly encouraging,” Sekhar said. “They suggest that GlyNAC supplementation could be a simple and viable method to promote and improve healthy aging in older adults. We call this the ‘Power of 3’ because we believe that it takes the combined benefits of glycine, NAC and glutathione to reach this far reaching and widespread improvement. We also have completed a randomized clinical trial on supplementing GlyNAC vs. placebo in older adults and those results will be forthcoming soon.”

Association found between consumption of ultra-processed foods and drinks and colorectal cancer risk

Barcelona Institute for Global Health (Spain), March 23, 2021

Consumption of ultra-processed foods and drink could increase the risk of developing colorectal cancer. This was the conclusion of a large study undertaken by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the “la Caixa” Foundation, based on questionnaires about food behaviours completed by around 8,000 people in Spain. The study, the first of its kind in the country, also analysed the relationship between ultra-processed food and drink products and two other cancers; while no association was observed with prostate cancer, in the case of breast cancer a higher risk was observed in the sub-group of former and current smokers who reported a diet high in ultra-processed products.

Social, economic and industrial changes have driven a rise in ultra-processed food and drink consumption, which currently accounts for between 25% and 50% of the total energy intake in diets in Europe and in high- and middle-income countries. The Nova classification system groups all foods and drinks into four categories according to how much processing they undergo. Ultra-processed foods–those that undergo the most processing–are industrial formulations with more than five ingredients which usually contain additional substances, such as sugar, fats, salt and additives. Examples of products in this category include sugary soft drinks, ready meals and mass-produced industrial baked goods.

Several studies have linked the consumption of ultra-processed foods and drinks to health risk factors, cardiovascular diseases, type 2 diabetes and an increased risk of premature death. There are only a few studies on the relationship of these food products with cancer and the results are not entirely conclusive. A French study found an association between the consumption of ultra-processed foods and an increased cancer risk. A Canadian study found an increased risk of developing prostate cancer with a higher intake of processed foods, but not with ultra-processed foods.

The aim of the present study was to assess whether the consumption of ultra-processed foods and drinks is associated with an increased risk of colorectal, breast or prostate cancer. To this end, the researchers undertook a case-control study of 7,843 adults living in different Spanish provinces: half of the participants had a diagnosis of colorectal (1,852), breast (1,486) or prostate cancer (953); and the other half were people with the same characteristics who did not have cancer. Data were obtained from the multicase-control study MCC-Spain. Dietary data was collected using a validated questionnaire designed to evaluate the frequency of consumption of usual food and drink items over a one-year period. The results were then classified according to the level of processing using the Nova classification.

The study, published in Clinical Nutrition, concluded that the consumption of ultra-processed foods and beverages is associated with an increased risk of colorectal cancer: a 10% increment in the consumption of ultra-processed foods and drinks was found to be associated with an 11% increase in the risk of developing colorectal cancer.

Dora Romaguera, first author of the study and researcher at ISGlobal, the Institut d’Investigació Sanitària Illes Balears (IdISBA) and the CIBEROBN, says that this relationship can be explained, in part, “by the low intake of fibre, fruits and vegetables, which are known to offer protection against colorectal cancer, among people who eat a lot of ultra-processed foods, but also by the additives and other substances with carcinogenic potential typically used in processed food products.”

In the case of breast cancer, no strong relationship was found, but an association was observed in the group of current and former smokers. Romaguera explains that “smoking is a risk factor for breast cancer, and smoking and certain dietary factors, such as the consumption of ultra-processed foods and beverages, are known to have synergetic effects on cancer development.”

No association was found between prostate cancer and a diet high in ultra-processed products. “This finding is not surprising and is consistent with the results of previous studies of dietary factors and prostate cancer risk, in which no link was found,” adds Romaguera.

Colorectal and Breast Cancer Cases: Less Healthy Diets

The results of the study showed that people with breast and colorectal cancer, but not those with prostate cancer, reported less healthy diets than people without cancer in the control group. “We found differences in terms of their intake of energy, fibre, energy density and saturated fatty acids. Consumption of ultra-processed foods and beverages was higher among colorectal and breast cancer cases than in the controls”, says ISGlobal researcher Sílvia Fernández, joint first author of the study.

The food groups that accounted for the largest proportion of ultra-processed food consumption were sugary beverages (35%), sugary products (19%), ready-to-eat foods (16%) and processed meats (12%). Processed meats have already been classified as carcinogenic by the International Agency for Research on Cancer (IARC). However, according to Pilar Amiano, researcher at the Guipúzcoa Public Health Service, which coordinated the study: “ultra-processed foods and drinks in general are not yet classified as carcinogenic because the aim of the IARC was not to assess the overall risk of an individual’s diet, but rather to focus on specific components that might be dangerous, such as processed meats”.

She goes on to say that, in light of the results of the present study and the current scientific evidence on the health risks associated with ultra-processed foods and drinks, in particular with respect to cancer, the authors believe “that food and public health policies and the IARC should already be taking food processing into account and discouraging the consumption of ultra-processed products”.

Hyperbaric oxygen therapy impact on telomere length and immunosenescence

Tel Aviv University (Israel), March 23, 2021

In a scientifically verified approach, signalling an important breakthrough in the study of aging,  Tel Aviv University and The Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Centerannounced today that, for the first time in humans, two key biological hallmarks of aging, telomere length shortening, and accumulation of senescent cells, can be reversed. The prospective clinical trial, published in peer-reviewed Journal Aging,  utilizes Hyperbaric Oxygen Therapy protocols to demonstrate cellular level improvement in healthy aging adults.

Hyperbaric Oxygen Therapy targets aging as a reversible disease

The prospective clinical trial is part of a comprehensive aging research program taking place in Israel. It was conducted by Prof. Shai Efrati, MD, from the Faculty of Medicine and Sagol School of Neuroscience at Tel Aviv University, and Amir Hadanny, MD, Chief Medical Research Officer of The Sagol Center for Hyperbaric Medicine and Research and co-author of the study. Using a specific protocol of hyperbaric oxygen therapy (HBOT), telomere length was significantly increased and senescent cells were reduced in a population of healthy aging subjects. The study was published in the peer-reviewed journal Aging. Titled: Hyperbaric Oxygen Therapy Increases Telomere Length and Decreases Immunosenescence in Isolated Blood Cells: A Prospective Trial.

A significant breakthrough in the study of aging

The biological deterioration of aging is cited as a major risk factor for cancer, cardiovascular diseases, diabetes, dementia, and Alzheimer’s disease. At the cellular level, two key hallmarks of the aging process are:

  1. The shortening of telomere length of approximately 20-40 bases per year, which is associated with a variety of serious life-threatening illnesses; and
  2. The accumulation of senescent cells, the so-called “old malfunctioning cells,” inhibit cell proliferation. The accumulation of senescence contributes to many age-associated conditions and illnesses, while the elimination of those cells can reverse them, as shown in previous animal studies.

The first study to evaluate telomere length and senescence

This is the first study to evaluate whether hyperbaric oxygen therapy can affect telomere length and senescence using a specific HBOT protocol. The trial included 35 healthy independent adults aged 64 and older. They did not undergo any lifestyle, diet, or medication adjustments.

How was the study conducted?

Each patient received 60 daily hyperbaric oxygen therapy sessions over the course of 90 days. Whole blood samples were collected prior to treatment, at the 30th and 60th session, and one to two weeks following the last HBOT session, to assess peripheral blood mononuclear cells (PMBCs) telomere length and senescence.

The holy grail of the biology of aging

“After dedicating our HBOT research to exploring its impact on the areas of brain functionality and age-related cognitive decline, we have now uncovered for the first time in humans hyperbaric oxygen therapy’s biological effects at the cellular level in healthy aging adults,” said Prof. Shai Efrati.

“Since telomere shortening is considered the ‘Holy Grail’ of the biology of aging, many pharmacological and environmental interventions are being extensively explored in the hopes of enabling telomere elongation.”

Significant improvement of telomere length

“The significant improvement of telomere length shown during and after these unique hyperbaric oxygen therapy protocols provides the scientific community with a new foundation of understanding that aging can, indeed, be targeted and reversed at the basic cellular-biological level.”

Improvement in just three months

Results found that the telomere length of T helper, T cytotoxic, natural killer, and B cells increased significantly. They rose by over 20 percent, following HBOT. The most significant change was in B cells, which increased during the 30th session, 60th session, and post HBOT by:

  • 25.68%±40.42 (p=0.007)
  • 29.39%±23.39 (p=0.0001)
  • 37.63%±52.73 (p=0.007)

In addition, there was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT.

“Until now, interventions such as lifestyle modifications and intense exercise were shown to have some inhibition effect on the expected telomere length shortening,”  explained Dr. Hadanny.

Midlife loneliness is a risk factor for Dementia and Alzheimer’s disease

Recovery from temporary loneliness may provide reduction in dementia risk

Boston University School of Medicine, March 14, 2021

Being persistently lonely during midlife (ages 45-64) appears to make people more likely to develop dementia and Alzheimer’s Disease (AD) later in life. However, people who recover from loneliness, appear to be less likely to suffer from dementia, compared to people who have never felt lonely.

Loneliness is a subjective feeling resulting from a perceived discrepancy between desired and actual social relationships. Although loneliness does not itself have the status of a clinical disease, it is associated with a range of negative health outcomes, including sleep disturbances, depressive symptoms, cognitive impairment, and stroke. Still, feeling lonely may happen to anyone at some point in life, especially under extreme and unresolved quickly circumstances such as the Covid-19 lockdowns. Yet, people differ in how long–or how “persistent”–they feel lonely for. Thus, it may be that people who recover from loneliness will experience different long-term consequences for their health than people who are lonely for many years.

In an effort to shed light on the relationship between these different forms of loneliness (transient and persistent loneliness) and the incident of AD, researchers from Boston University School of Medicine (BUSM) examined data involving cognitively normal adults from the Framingham Heart Study. Specifically, they investigated whether persistent loneliness more strongly predicted the future development of dementia and AD than transient loneliness. They also wanted to see whether this relationship was independent from depression and established genetic risk factors for AD, such as the Apolipoprotein ε4 (APOE ε4) allele.

After taking effects of age, sex, education, social network, living alone, physical health and genetic risk into account, persistent loneliness was associated with higher risk, whereas transient loneliness was linked to lower risk of dementia and AD onset after 18 years, compared with no loneliness.

“Whereas persistent loneliness is a threat to brain health, psychological resilience following adverse life experiences may explain why transient loneliness is protective in the context of dementia onset,” explained corresponding author Wendy Qiu, MD, PhD, professor of psychiatry and pharmacology & experimental therapeutics at BUSM. In light of the current pandemic, these findings raise hope for people who may suffer from loneliness now, but could overcome this feeling after some time, such as by using successful coping techniques or following a policy change in the physical distancing regulations.

According to the researchers, these results motivate further investigation of the factors that make individuals resilient against adverse life events and urges to tailor interventions to the right person at the right time to avert persistency of loneliness, promote brain health and AD prevention.

Resveratrol inhibits macrophage infiltration of pancreatic islets in type 1 diabetes

Nahda University (Egypt), March 16, 2021

According to news reporting originating in Beni Suef, Egypt, research stated, “Despite CXC chemokine ligand 16 (CXCL16) contributes to the pathogenesis of many inflammatory disorders, the mechanism by which CXCL16 is involved in T1DM remains unclear. In this study, we examined the role of the CXCL16/NF-kB p65 signaling pathway in the progression of this disease and the possible protective effect of resveratrol (RES) on streptozotocin (STZ)-induced T1DM.”

The news reporters obtained a quote from the research from Nahda University, “Mice were classified into four groups of 10 animals each. The control group received citrate buffer. The RES group received 50 mg/kg i.p. RES for 12 days beginning on day 4 of citrate buffer. The STZ group received 55 mg/kg i.p. STZ once a day for 5 consecutive days. The fourth group injected with RES (50 mg/kg) for 12 days starting on day 4 of STZ injection. Biochemical, physical and oxidative stress parameters were measured in all groups. Moreover, expression of CXCL16 and CD45 was measured in pancreatic islets and spleen. Additionally, NF-kB p65 was investigated in isolated islets. Our results showed a significant elevation of CXCL16, NF-kB p65 and CD45 in islets of diabetic (DM) mice. Intriguingly, RES significantly restored distorted biochemical, physical and oxidative stress parameters after STZ treatment as well as inhibited the expression of CXCL16/NF-kB p65 in pancreatic islets. Moreover, RES normalized CXCL16 and CD45 expression in islets and spleen.”

According to the news reporters, the research concluded: “This study demonstrates first evidence that CXCL16/NF-kB p65 signaling pathway is associated with macrophage infiltration to pancreatic islet in T1DM and that RES successfully improved T1DM may be at least via inhibiting this pathway.”

This research has been peer-reviewed.

Boosting enzyme with NAD+ may help improve blood flow, fitness in elderly

University of Pennsylvania, March 22, 2018 

As people age, their blood-vessel density and blood flow decrease, which is why it’s harder to maintain muscle mass after 40 and endurance in the later decades, even with exercise. This vascular decline is also one of the major causes of age-related diseases, such as frailty or hypertension. However, little is known about the underlying cause or how to stop it.

Now, in a new study published this week in Cell, a team of researchers from Penn Medicine and other institutions have shown for the first time how a well-studied enzyme called SIRT1 declines in the blood vessels with age and that restoring it reverses the effects of vascular aging. After receiving a supplement called NAD+ precursor nicotinamide mononucleotide (NMN), older mice had the number of capillaries and capillary density found in much younger mice, and improved endurance by up to 80 percent. The collaborative study also involves researchers from Harvard Medical School and Massachusetts Institute of Technology.

“This study tells us that the loss of SIRT1 is a primary reason why our ability to exercise and receive its benefits diminish as we age,” said co-senior author Zoltan Pierre Arany, MD, PhD, an associate professor of Cardiovascular Medicine in the Perelman School of Medicine at the University of Pennsylvania. “We also show that when we bring the enzyme back into the blood vessels, vascular health improves dramatically: The old blood vessel tree [cluster of capillaries] in the older mice is turned into a young vessel tree, one that looks like it’s been exercising for a while, just by turning on this enzyme. That’s the most powerful aspect of the study.”

The preclinical results show for the first time the ability to improve vascular health by increasing SIRT1, but they also have important implications for the prevention of age-related diseases, including cardiovascular disease, and aging itself. Identifying a target such as an enzyme that could be restored in a person’s vessels is an important step that could lead to new or modified existing therapeutics to treat diseases or slow down aging.

SIRT1 is a member of a family of enzymes that mediate the health benefits of diet and can extend lifespan when overexpressed, researchers have shown in past studies. It’s known that in young muscle SIRT1 is required for developing new and stronger blood vessels and is implicated in the deterioration of cells that line vessels. It was, however, unknown whether SIRT1 regulates vascular health in skeletal muscle tissue, and if so, whether its breakdown with age was reversible.

To test if SIRT1 was required for vessel creation and maintenance, the researchers knocked out its gene in mice and found that the density and number of capillaries was significantly lower compared to untreated mice, who in a high intensity endurance test ran twice as long as the mice without SIRT1.

Now, knowing that SIRT1 was necessary for vascularization, the researchers administered the NMN supplement to 18-month-old mice for two months and compared their blood vessels to six-month-old mice. NMN restored the number of capillaries and capillary density of the old mice to those typically seen in young mice and also dramatically increased their oxygen consumption. The most striking effect was a 56 to 80 percent improvement in endurance during a high-intensity, treadmill exercise test. Combining hydrogen sulfide, another molecule known to increase SIRT1, with NMN also increased capillary density in mice as old as 32 months compared to younger mice.

To the authors’ knowledge, this is the first time small molecules have induced the formation of new blood vessels at an advanced age in an animal model.

Overall, the researchers show in mice that loss of SIRT1 resulted in an early decline in skeletal muscle vascular density and exercise capacity, while overexpression of SIRT1 in older mice had a protective effect, ostensibly by sensitizing these cells to vascular endothelial growth factor coming from muscle fibers, the authors said.

The next step, Arany said, is to look for evidence of this mechanism at play in humans and for a more robust pharmaceutical agent that would be appropriate and effective for use in the clinic. NMN supplements marketed as having anti-aging properties exist today, but very few, if any, have clinical evidence to back up that claim. Researchers also used a larger dosage in the study compared to what’s on the market.

“We know that enzymes that regulate the fundamental metabolic program can go awry with age,” Arany said. “And we now know that turning that around and fixing it improves the health of aging blood vessels, sufficiently enough so that we can see differences in performance such as exercise capacity. We are still a long way away from testing in humans, but this gives us direction, a target to work with.”