Restoring NAD+ could reduce DNA damage accumulation
University of New South Wales (Australia) March 24 2020.
The March issue of Science reports the finding of Professor David A. Sinclair and colleagues of an ability for a precursor of nicotinamide adenine dinucleotide (NAD+) to increase the repair of DNA damage that results from aging or exposure to radiation.
“This is the closest we are to a safe and effective anti-aging drug that’s perhaps only three to five years away from being on the market if the trials go well,” announced Dr Sinclair, of the University of New South Wales in Sydney, Australia.
Dr Sinclair’s team discovered that the protein known as DBC1 (deleted in breast cancer 1) contains a domain that binds NAD+, the oxidized form of the coenzyme NAD that occurs in all living cells. Binding of NAD+ inhibits the interaction of DBC1 with PARP1, a DNA repair protein. With aging, NAD+ levels decline and DBC1 is increasingly bound to PARP1. When this occurs, PARP1’s repair activity is reduced—a process that can be reversed by restoration of NAD+ levels.
The mechanism could explain the rejuvenating effects of NAD+ supplementation in older animals. Cells of mice treated with the NAD+ precursor nicotinamide mononucleotide (NMN) showed improvement in repair of DNA damage caused by aging or radiation exposure. “The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” Dr Sinclair reported.
Dr Sinclair is noted for his earlier research involving resveratrol, a compound that activates the enzyme SIRT1 which may be responsible for some of the benefits of calorie restriction. “While resveratrol activates SIRT1 alone, NAD+ boosters activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he noted.
Drinking Tea Supports a Healthy Brain
National University of Singapore School of Medicine, March 23, 2020
Research reported in the journal Aging revealed a brain benefit in association with regularly drinking tea.*
Acting on the results of previous research that found a reduction in the risk of cognitive decline among daily tea drinkers, the current study compared 15 tea drinkers aged 60 and older to 21 participants in the same age group who did not regularly consume tea.
Neuropsychological tests evaluated cognitive function and magnetic resonance imaging assessed brain connectivity. Participants who regularly consumed tea had better organized brain regions and cognitive function compared to those who were not tea drinkers.
The authors noted that, “Tea has been a popular beverage since antiquity, with records referring to consumption dating back to the dynasty of Shen Nong (approximately 2700 BC) in China.” They went on to say that drinking tea has become increasingly popular in western countries today.
The study was led by Research Assistant Professor Feng Lei, of the National University of Singapore School of Medicine, with collaborators from the University of Essex and University of Cambridge.
Editor’s Note: “Our results offer the first evidence of positive contribution of tea drinking to brain structure and suggest that drinking tea regularly has a protective effect against age-related decline in brain organization,” said Dr. Feng Lei.
*Aging (Albany NY). 2019 Jun 14;11(11): 3876-3890.
Green Tea Helps Cystitis Sufferers and Prevents Antibiotic Resistance
Kerman University of Medical Sciences (Iran), March 20, 2020
A frequently prescribed antibiotic combination, trimethoprim-sulfamethoxazole, is used to treat many types of infection, including bronchitis, middle ear infections and cystitis, a common infection of the bladder.[i] Sold under the brand names Bactrim®, Bactrim BS® and Sulfatrim Pediatric®, these antibiotics, jointly called co-trimoxazole, have proven effective against E. coli, the bacteria responsible for up to 95% of cystitis infections.[ii]
But the overuse of antibiotics worldwide has caused many bacterial strains, including E. coli, to become increasingly drug-resistant, prompting scientists to explore the use of anti-microbial herbs in combination with antibiotics in order to boost their efficacy.
Co-trimoxazole has been shown in clinical studies to have synergistic effects when combined with green tea catechins, powerful antimicrobials and active polyphenols in green tea.[iii]
Study Offers Hope in Green Tea as Aid to Cystitis Sufferers
These synergistic effects were explored by researchers at Kerman University of Medical Sciences in Kerman, Iran, in a pioneering clinical trial investigating green tea as an adjunct therapy for treatment of cystitis in women.
In this triple-blind, randomized trial, researchers selected 35 patients from a sample group of healthy, premenopausal, non-pregnant adult women between 18 and 50 years of age with acute uncomplicated cystitis.
Women with complicating factors such as diabetes, discharge or vaginitis, as well as regular green tea drinkers were excluded from consideration. Researchers hypothesized that the response rate to co-trimoxazole would be around 50%, and that this rate would rise to around 80% by adding green tea to patients’ daily intake.
To test their hypothesis, 107 patients were allocated into one of two groups, experimental or placebo (control). Participants were assigned to receive four 500-milligram (mg) capsules of green tea in the experimental group, while the control group received the same number of starch-only capsules with identical shape, color and packaging.
Both groups were dosed daily for a period of three days, while also receiving the standard course of antibiotic treatment: two 480-mg tablets of co-trimoxazole twice daily for three days.
Green Tea Has Powerful Antimicrobial Effects
Green tea is known for powerful healing properties, including the ability to fight viral infections and prevent periodontal disease. In prior studies on the antimicrobial effect of green tea for UTIs, it has been noted that effectiveness is enhanced when green tea is administered before bed due to the retention of therapeutic catechins in the bladder overnight.[iv]
Study authors noted that more than 90% of the antimicrobial agents in green tea are excreted in the first eight hours after ingestion, therefore the patients received their capsules in the evening during the study period.[v]
The presence of acute uncomplicated cystitis symptoms was recorded via urinalysis at baseline and also on the fourth day at the end of the study period. Patients were screened for symptoms during the three-day trial via phone consultation.
Patients whose symptoms were not resolved on the fourth day were referred to physicians for further treatment, and patients were asked to return to the clinic at two, four and six weeks post-commencement for physician assessment of the symptoms of recurrent uncomplicated cystitis.
Green Tea Helps Women Treat Uncomplicated Cystitis
Of the 107 eligible participants, 70 women completed the trial. Women in the green tea group showed a statistically significant decrease in the prevalence of cystitis symptoms at each time point after initiating treatment in comparison with the placebo group.
Meanwhile, the addition of the green tea resulted in a statistically significant improvement in urinalysis results (abnormal urine color, the presence of pus and bacteria in the urine), with the exception of blood in the urine (hematuria), after three days of treatment.
Regarding side effects of treatment, seven patients in the placebo group and six in the green tea group reported mild nausea that was resolved within two days. There was no statistically significant difference in the incidence of nausea between the two groups. No other significant side effects were reported.
In the placebo group, 63% of the patients remained symptomatic, 37.1% had bacteriuria and 57.1% had pyuria on urinalysis after three days of co-trimoxazole therapy, suggesting that there is a high prevalence of co-trimoxazole resistance among E. coli strains in the urinary tract for individuals in this geographic region (Kerman, Iran).
Previous in vitro studies in Iran have reported that more than 47% of the E. coli isolates from patients with UTIs were resistant to cotrimoxazole.[vi], [vii] However, in the green tea group, almost all the patients responded to the treatment.
If the response rates were related to the synergistic effects of green tea catechins, it suggests that adding green tea to co-trimoxazole therapy could be a way to decrease and control the rates of co-trimoxazole resistance among uropathogenic E. coli strains.[viii]
In their final analysis, researchers concluded that green tea was an effective adjunct to trimethoprim-sulfamethoxazole therapy for treating acute uncomplicated cystitis in women. They concluded that this result could be related to antibacterial effects of green tea catechins and its synergistic effects when taken in conjunction with standard antibiotic treatment.[ix]
Cystitis: A Common Infection for Women
Common or “uncomplicated” cystitis is a bacterial infection of the bladder that is the most prevalent type of urinary tract infection (UTI) in women,[x] spurring more than 6 million trips to the doctor every year in the U.S.[xi]
Cystitis is typically caused when E. coli bacteria enter the bladder through the urethra, although other types of bacteria can also cause cystitis.[xii] Cystitis can occur as a reaction to certain drugs or radiation treatment, or in response to irritants such as feminine hygiene sprays and spermicides.[xiii]
Health factors like having a blocked bladder or loss of bowel control create conditions where bacteria are more prevalent around the urethra. These bacteria move up the urethra and into the bladder causing cystitis, which is why illnesses requiring the use of a urinary catheter increase the likelihood of developing a UTI.[xiv]
Women generally become more susceptible to cystitis if they are older, pregnant, diabetic or confined to bed rest for long periods of time
Extract from seeds of the Melinjo tree may improve obesity and diabetes
Kumamoto University (Japan), March 24, 2020
In Southeast Asia, the fruit, flowers, and leaves of Indonesia’s “Melinjo” tree are traditional foods. Researchers from Kumamoto University, Japan who study plants from around the world for useful medicinal properties have found that Melinjo seed extract (MSE) stimulates the production of adiponectin, a beneficial hormone that improves obesity and diabetes. They also discovered that individual genotype differences were responsible for variations in its efficacy.
Melinjo fruit have high antioxidant and antibacterial qualities and are known to contain large amounts of polyphenols. One such compound, resveratrol, has been shown to induce adiponectin and may improve lifestyle-related diseases like metabolic syndrome. Gnetin C, a type of resveratrol abundant in MSE, is known to have higher antioxidant activity and stays in the body longer than resveratrol. However, the detailed mechanism by which these compounds exert their biological activity is still unknown.
Kumamoto University’s Global Center for Natural Resources Sciences conducts component isolation and identification of useful plants and natural products from around the world and evaluates their pharmacological activities. Within the center, Dr. Kentaro Oniki’s research team used genetic analysis to find that differences in the type of DsbA-L (Disulfide-bond-A oxidoreductase-like protein) gene affects adiponectin activation. In other words, DsbA-L induction may promote adiponectin activation and improve lifestyle-related diseases. In their recent work, they attempted to determine 1) whether MSE enhances the function of DsbA-L, 2) whether MSE promotes adiponectin activation, and 3) whether MSE has a therapeutic effect on obesity and diabetes.
In their first study (double-blind, placebo-controlled, randomized controlled), 42 healthy adult men took MSE supplements orally for 14 days. They found that taking 300 mg of MSE per day activated adiponectin in human males. They also found that effects varied depending on the differences in the type of DsbA-L gene (G/G, G/T, T/T) possessed by the individual. MSE effects were large in G/T or T/T genotype carriers whose gene expression level was presumed to be low.
Following the results of the clinical trials, another of the center’s researchers, Dr. Tsuyoshi Shuto, and his research team tested the compound in a high fat diet mouse model with obesity-induced diabetes. By measuring the effects of MSE on DsbA-L expression and blood adiponectin concentration in various tissues, they found that daily oral administration of MSE over a period of four weeks increased the expression of DsbA-L and the amount of activated adiponectin in the body. Diabetic pathologies, in muscle tissue also improved. Symptoms such as increased fat accumulation and fasting blood sugar levels significantly improved.
These research results show that MSE promotes DsbA-L expression, increases the amount of activated adiponectin, and may improve obesity and diabetic symptoms in living organisms, especially in mice.
“We believe that our findings can benefit human health through the treatment of obesity and diabetes by focusing on the induction of the DsbA-L gene using MSE,” said Associate Professor Shuto. “We hope that this work contributes to a healthier society through the creation of innovative medicines and products from plants and other natural resources. It is important to provide solid scientific evidence that supports the use of natural resources in emerging countries and using them for beneficial drug discovery and health.”
Walking more linked with lower blood pressure
A new study has found that people who walk more also have lower blood pressure. This confirms existing notions that keeping active is good for cardiovascular health.
University of California in San Francisco, March 24, 2020
People who walk more also have lower blood pressure, according to a recent study.
Abnormally high blood pressure (hypertension) affects almost half of the United States’ adult population, and it is one of the main risk factors for more serious cardiovascular conditions and events, such as heart disease and stroke.
Past research has shown that one way of preventing hypertension is through regular exercise, and now, a new study may add to the evidence that physical activity helps safeguard cardiovascular health.
The study — led by researchers from the University of California in San Francisco — found a link between how much a person walks each day and their blood pressure levels.
Walking may help cardiovascular health
The researchers looked at data collected from 638 participants enrolled in the Framingham Heart Study. These participants wore an Apple Watch every day, for at least 5 hours each time.
The smart watch recorded the number of steps they took on a daily basis. The volunteers also recorded their own blood pressure at home on a weekly basis for the duration of the study — which lasted about 5 months.
Over the study period, the researchers noted that the participants’ average systolic blood pressure, which is the blood pressure when the heart contracts, was 122 millimeters of mercury (mm Hg).
Their average diastolic blood pressure, which is the blood pressure when the heart relaxes, was 76 mm Hg.
Both of these measurements indicate normal to slightly elevated blood pressure, according to the latest guidelines issued by the American College of Cardiology and the American Heart Association.
The study researchers found — after having accounted for possible confounding factors — that for every 1,000 steps a participant took per day, their systolic blood pressure was approximately 0.45 points lower.
This suggests that a person who takes about 10,000 steps each day has a 2.25 points lower systolic blood pressure than someone who takes half that amount of steps.
On average, over the 5-month period, participants took about 7,500 steps a day.
Although the study was observational and did not aim to ascertain causal relationships, the investigators argue that it adds to the evidence that regular physical activity can help protect cardiovascular health.
“Measuring habitual physical activity in community-based settings in this way distinguishes our study from prior studies that have looked at either self-reported physical activity or used accelerometers to measure daily activity for only a short amount of time, usually about a week,” notes lead author Dr. Mayank Sardana.
Teens who are bullied struggle with long-term mental health issues
University of Michigan, March 24, 2020
Bullying can make life miserable in the short term for teens, but its impact can also linger into young adulthood, says a University of Michigan researcher.
Much is known about the negative effects of bullying, ranging from depression to poor performance in school, but a new study indicates that bullied teens can suffer long-term mental health problems that last into early adulthood.
How these individuals perceive themselves contributes to these outcomes, said study author Janette Norrington, U-M doctoral student in sociology. The study, which appears in the journal Youth & Society, also indicates that verbal abuse and peer harassment are more harmful than physical victimization or social exclusion.
Previous research has shown that youths suffer short-term mental health consequences, but less is known about the negative, long-term impact between the ages 18 to 24.
Norrington used longitudinal data from the Panel Study of Income Dynamics to examine teen self concept as a mediator in the relationship between adolescent peer victimization and psychological distress in emerging adulthood.
Self-concept, which is the image people have of themselves or self worth, is a link between teen bully victimization and later mental health. Bullying includes physically harming, making fun of, excluding, and spreading rumors about a person.
“Bully victimization damages how people view themselves in adolescence and that negative view can linger into adulthood, contributing to poor mental health,” she said.
Norrington examined the responses of more than 1,400 adolescents in 2002 and 2007, who were questioned about the frequency that classmates hit them and picked on them, had their things (money and lunch) taken and were left out of friends’ activities. In 2009 and 2013, as adults, they were asked how often in the past month they felt nervous, hopeless, sad and worthless.
Peer victimization was still associated with higher levels of psychological distress, but the impact lessened among those who had high self-esteem, the study found.
Intervention and mental health programs should focus on enhancing the self-concept of adolescent bully victims, Norrington said. One way to do this would be to emphasize peer support to help youth feel valued and develop self-confidence.
Anxious about COVID-19? Stress can have lasting impacts on sperm and future offspring
University of Maryland School of Medicine, March 24, 2020
Prolonged fear and anxiety brought on by major stressors, like the coronavirus pandemic, can not only take a toll on a person’s mental health, but may also have a lasting impact on a man’s sperm composition that could affect his future offspring. That is the finding of a provocative new study published in the journal Nature Communications by researchers at the University of Maryland School of Medicine.
The research outlines a biological mechanism for how a father’s experience with stress can influence fetal brain development in the womb. The effects of paternal stress can be transferred to offspring through changes in the extracellular vesicles that then interact with maturing sperm. Extracellular vesicles are small membrane-bound particles that transport proteins, lipids, and nucleic acids between cells. They are produced in large amounts in the reproductive tract and play an integral role in sperm maturation.
“There are so many reasons that reducing stress is beneficial especially now when our stress levels are chronically elevated and will remain so for the next few months,” said study corresponding author Tracy Bale, PhD, Professor of Pharmacology and Director of the Center for Epigenetic Research in Child Health & Brain Development at the University of Maryland School of Medicine. “Properly managing stress can not only improve mental health and other stress-related ailments, but it can also help reduce the potential lasting impact on the reproductive system that could impact future generations.”
She and her colleagues did not specifically study those who were under stress due to the coronavirus pandemic.
To examine a novel biological role for extracellular vesicles in transferring dad’s stress to sperm, the researchers examined extracellular vesicles from mice following treatment with the stress hormone corticosterone. After treatment, the extracellular vesicles showed dramatic changes in their overall size as well as their protein and small RNA content.
When sperm were incubated with these previously “stressed” extracellular vesicles prior to fertilizing an egg, the resulting mouse pups showed significant changes in patterns of early brain development, and as adults these mice were also significantly different than controls for how they responded to stress themselves.
To see if similar differences occurred in human sperm, the researchers recruited students from the University of Pennsylvania to donate sperm each month for six months, and complete questionnaires about their perceived stress state in the preceding month. They found that students who had experienced elevated stress in months prior showed significant changes in the small RNA content of their sperm, while those who had no change in stress levels experienced little or no change. These data confirm a very similar pattern found in the mouse study.
“Our study shows that the baby’s brain develops differently if the father experienced a chronic period of stress before conception, but we still do not know the implications of these differences,” said Dr. Bale. “Could this prolonged higher level of stress raise the risk for mental health issues in future offspring, or could experiencing stress and managing it well help to promote stress resilience? We don’t really know at this point, but our data highlight why further studies are necessary.”
The research team did find that stress-induced changes in the male reproductive system take place at least a month after the stress is attenuated and life has resumed its normal patterns. “It appears the body’s adaptation to stress is to return to a new baseline,” Dr. Bale said, “a post-stress physiological state – termed allostasis.”
This research was funded by the National Institute of Mental Health and included co-authors from the Institute for Genome Sciences at the University of Maryland School of Medicine and the Department of Pharmaceutical Science at the University of Maryland School of Pharmacy, as well as the University of Pennsylvania.
“This research represents a critical step in understanding important mechanisms that underlie the field of intergenerational epigenetics,” said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. “Such knowledge is crucial to identify early interventions to improve reproduction and early childhood development down the road.”
While the study did not test stress management interventions to determine what effects they might have on attenuating the changes in sperm composition, Dr. Bale, who goes for regular runs to reduce the stress of the current COVID-19 pandemic, contends that any lifestyle habits that are good for the brain are likely good for the reproductive system.
“It is important to realize that social distancing does not have to mean social isolation, especially with modern technologies available to many of us,” said Joshua Gordon, Director of the National Institute of Mental Health in his web message about coping with coronavirus. “Connecting with our friends and loved ones, whether by high tech means or through simple phone calls, can help us maintain ties during stressful days ahead and will give us strength to weather this difficult passage.”
The Centers for Disease Control and Prevention has tips on “stress and coping” page on their COVID-19 site that recommends the following to “support yourself”:
- Take breaks from watching, reading, or listening to news stories, including social media. Hearing about the pandemic repeatedly can be upsetting.
- Take care of your body. Take deep breaths, stretch, or meditate. Try to eat healthy, well-balanced meals, exercise regularly, get plenty of sleep, and avoid alcohol and drugs.
- Make time to unwind. Try to do some other activities you enjoy.
- Connect with others. Talk with people you trust about your concerns and how you are feeling.
Inactive teens develop lazy bones, study finds
University of British Columbia, March 23, 2020
Inactive teens have weaker bones than those who are physically active, according to a new study.
Researchers with UBC and the Centre for Hip Health and Mobility, at the Vancouver Coastal Health Research Institute, measured the physical activity and bone strength of 309 teenagers over a specific four-year period that is crucial for lifelong, healthy skeletal development.
“We found that teens who are less active had weaker bones, and bone strength is critical for preventing fractures,” said Leigh Gabel, lead author and PhD candidate in orthopedics at UBC.
Gabel and her co-investigators used high resolution 3D X-ray images to compare differences between youth who met the daily recommendation of 60 minutes of moderate-to-vigorous physical activity per day and those who got less than 30 minutes a day. The four-year window – between the ages of 10 to 14 for girls and 12 to 16 for boys – is a vital time when as much as 36 per cent of the human skeleton is formed and bone is particularly responsive to physical activity.
“Kids who are sitting around are not loading their bones in ways that promote bone strength,” said Gabel, which is why weight-bearing activities such as running and jumping and sports like soccer, ultimate Frisbee and basketball are important.
Bone strength is a combination of bone size, density and microarchitecture. While boys had larger and stronger bones throughout the study, both boys and girls responded in the same way to physical activity.
“We need school-and community-based approaches that make it easier for children and families to be more active,” said co-author Heather McKay, a professor in orthopedics and family practice at UBC and the Centre for Hip Health and Mobility. The good news is that activity does not have to be structured or organized to be effective: short bursts such as dancing at home, playing tag at the park, chasing your dog or hopping and skipping count, too. Parents and caregivers can support healthy choices by being role models and limiting screen time. McKay highlights simple yet effective tactics used in the Action Schools! BC intervention where children and their teachers took activity breaks throughout the day during lessons.
“The bottom line is that children and youth need to step away from their screens and move to build the foundation for lifelong bone health,” said McKay.
High-Intensity Interval Training (HIIT) Reverses Aging
Mayo Clinic, March 14, 2020
Mayo Clinic study shows that high-intensity aerobic exercise performed in short intervals can reverse the aging processes.
The Mayo Clinic has determined that intense aerobic exercise has the potential to reverse the aging process in adults. Though everyone knows exercise is beneficial, there are plenty of questions regarding which types of exercises are the best and what age groups benefit the most from specific exercises. According to the Mayo Clinic, high intensity cardio can reverse some cellular aspects of aging
The Study’s Aim
The purpose of the study described above was to pinpoint evidence that would assist in the development of exercise recommendations and targeted therapies for people of varying ages. Researchers monitored molecular and metabolic alterations in individuals of varying ages across a period of about three months. They collected data 72 hours after those in randomized groups performed an array of different exercises.
Mayo Clinic researchers tested high-intensity interval training (HIIT) against combined training and resistance training. Each style of training boosted lean body mass as well as insulin sensitivity. However, HIIT and combined training heightened aerobic capacity as well as mitochondrial functionality for skeletal muscle. This is especially important for senior citizens who often endure declines in mitochondrial content and functionality.
HIIT even boosted muscle protein content that improved energetic functions and spurred the enlargement of muscles. This bolstering of muscle protein was common in older adults who engaged in high-intensity intervals. The research team keyed in on one of their most important findings: exercise boosted the cellular machinery necessary for the construction of new proteins. Protein creation and synthesis reverse some of the problematic effects of the aging process.
The take-home message is that HIIT is ideal for aging adults as it benefits the body at the molecular level as well as metabolically. HIIT reverses certain manifestations of the aging process within the human body’s protein function. Engaging in resistance training is also advisable as it allows for the establishment of considerable muscle strength. HIIT is certainly beneficial yet a strict reliance on this style of exercise won’t significantly boost muscle strength unless combined with resistance training.
More Details About the Findings
The researchers found that training has minimal effect on DNA energy transfer within skeletal muscle but facilitated such muscle protein expression to a high degree in older individuals. Though mitochondrial cell functionality dissipates with age, it heightens with training. Exercise drastically increased ribosomal proteins designed to boost new proteins. Exercise also heightened skeletal muscle gene expression regardless of age.
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