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News flashes are posted here frequently to keep you up-to-date with the latest advances in health and longevity. We have an unparalleled track record of breaking stories about life extension advances.

Preclinical research suggests flavonoid could benefit Alzheimer disease patients

August 30 2023. A study that evaluated the effect of the flavonoid luteolin in a mouse model of Alzheimer disease resulted in improvement in cognitive deficits and other factors associated with the disease. The findings were reported in the October 2023 issue of Redox Biology.

Mice bred to develop Alzheimer disease were given a low dose of luteolin, a high dose of luteolin or no treatment for 8 weeks. Another group of mice that were not bred to develop the disease were used as controls. Behavioral tests were conducted at the end of the treatment period and the animals' brains were examined. Mice that received luteolin had less cognitive impairment compared with untreated Alzheimer disease mice.

Treated animals showed a reduction in amyloid beta (a sticky protein that forms plaques in the brains of Alzheimer disease patients) in the hippocampi of their brains, an area involved in memory. Amyloid beta generation and accumulation was also reduced in luteolin-treated cultured neurons derived from Alzheimer disease mice.

The researchers found an increase in the activity of the antioxidants superoxide dismutase and glutathione in luteolin-treated animals, while malondialdehyde, a marker of oxidative stress, was lower in comparison with levels measured untreated Alzheimer mice. Genesis of mitochondria (the cells' power plants) and mitochondrial function were enhanced in luteolin-treated mice and apoptosis (programmed cell death) of cells known as neurons was reduced.

"This study clearly demonstrated, for the first time, that luteolin administration was able to alleviate the cognitive deficits, anxiety degree and exploring ability in a triple transgenic Alzheimer disease mouse model.," authors Zhijun He of Wuhan Polytechnic University and colleagues wrote. "In conclusion, although further investigation is necessary, our findings provide a theoretical basis for the development of luteolin as a potential candidate for treating Alzheimer disease."

—D Dye

Added zinc associated with better lipid profiles among diabetics

August 28 2023. A systematic review and meta-analysis published August 19, 2023, in Advances in Nutrition revealed improvements in low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol and triglyceride levels among men and women with type 2 diabetes who were given zinc.

People with type 2 diabetes have an increased prevalence of high blood lipids, high blood pressure, kidney dysfunction and other disorders.

The meta-analysis included 14 randomized, controlled trials that examined the effects of zinc on lipids among a total of 1,067 participants with type 2 diabetes. A significant reduction in LDL cholesterol, total cholesterol and triglycerides was observed among participants who were given the mineral. An inverse association was found between these declines and receiving zinc for less than 12 weeks. Furthermore, analysis of the 13 studies that reported HDL cholesterol levels found a significant increase in HDL among participants who were given zinc. Dose-response analysis revealed optimum elemental zinc doses of greater than 100 mg, 120 mg and 140 mg per day respectively associated with reductions in LDL cholesterol, total cholesterol and triglycerides. No studies reported adverse events or toxicity in association with zinc.

Authors Mohammad Heidari Seyemahalleh and colleagues at Tehran University of Medical Sciences noted that "Studies have shown that pharmacological doses of zinc, which ranges between 100 and 300 mg daily, are standard clinical recommendation dose for short-term practices."

They concluded that zinc "significantly improved lipid profile in patients with type-2 diabetes mellitus. The findings of our research can help practitioners in the process of treating and improving the complications caused by type 2 diabetes, although our findings are mostly aimed at patients with low serum zinc levels and not at patients under long-term zinc."

—D Dye

Study supports aspirin guidelines

August 25 2023. The annual meeting of the European Society of Cardiology was the site of a presentation by Anna Meta Kristensen, MD, of the finding of an increased risk of heart attack, stroke or death following a first heart attack among people who did not use prophylactic aspirin as prescribed.

"We recommend that all patients who have had a heart attack stay adherent to their aspirin in accordance with guidelines until randomized controlled trials have proven otherwise, and clinical guidelines have been changed," Dr Kristensen stated.

The investigation, which included 40,114 men and women whose first heart attacks occurred during 2004–2017, involved patients treated with a coronary stent who were prescribed aspirin during the first year following the event. "We assessed the effects of long-term aspirin use in patients who were not receiving other medications for the prevention of heart attack or stroke," Dr Kristensen remarked. "Both anticoagulants and P2Y12 inhibitors are agents that, similar to aspirin, work to prevent the formation of blood clots. Therefore, patients undergoing such treatments were excluded from our study."

Patients' adherence to aspirin regimens was evaluated via prescription records. Those who used aspirin more than 80% of the time were considered adherent. In comparison with patients who used aspirin consistently after their initial heart attack, the composite risk of stroke, death or recurrent heart attack among those who were nonadherent was 29%, 40%, 31% and 20% greater two, four, six and eight years later, respectively.

"Our findings cannot be generalized to all patients who experience a heart attack, as our study specifically focused on those who received treatment with a coronary stent and were not taking other medications to prevent blood clot formation," Dr Kristensen noted. "With that in mind, the results support current guidelines recommending long-term aspirin after a heart attack."

—D Dye

Lower risk of relapse, death during follow-up among cancer patients given vitamin D

August 23 2023. On August 22, 2023, JAMA Network Open reported an analysis of a trial which revealed a reduction in the risk of digestive tract cancer relapse or death during a 3.5-year median follow-up period among men and women who received vitamin D compared with those who received a placebo.

The study included 37 patients with esophageal cancer, 170 patients with gastric cancer, 2 patients with small bowel cancer and 183 patients with colorectal cancer enrolled in the AMATERASU randomized clinical trial between January 2010 and February 2018. Patients' tumors were analyzed for the expression of p53, a protein that helps prevent cells from becoming malignant. The p53 protein can be mutated in people with cancer, which encourages the cancer to grow and become more difficult to treat. Serum antibodies to mutated p53 were detected among 142 patients.

"The main findings of this study were that daily supplementation of 2000 IU of vitamin D reduced the risk of relapse or death by 27% compared with placebo in the p53-immunoreactive subgroup, defined by positivity for p53-antibody in serum and p53 protein in more than 99% of cancer cells," authors Kazuki Kanno, MD, and colleagues reported.

In an Invited Commentary in the same issue of the journal, vitamin D authority Michael F. Holick, PhD, MD, called the finding "a game changer" and suggested that most cancer patients improve their vitamin D status.

"It is well-documented that in order to achieve a circulating concentration of 25(OH)D above 30 ng/mL requires a vitamin D intake of at least 2000 IUs daily, an amount that cannot be achieved from diet alone," he remarked. "Although vitamin D is the sunshine vitamin you cannot get enough vitamin D from sun exposure unless you expose more than 20% of your body surface to sunlight almost daily like the Maasai and Hazda do in equatorial Africa."

—D Dye

How melatonin supports memory

August 21 2023. The June 7, 2023, issue of NeuroReport reported the findings of Atsuhiko Chiba and colleagues at Sophia University in Japan of mechanisms for the sleep-inducing hormone melatonin in memory enhancement.

The research team evaluated the effects of melatonin, its breakdown product known as N1-acetyl-5-methoxyquinuramine (AMK) and ramelteon, which binds and activates the melatonin receptor. They also studied the effects of a process called phosphorylation (the addition of phosphate groups to molecules or ions) in five proteins involved in memory formation: ERK, CaMKIIα, CaMKIIβ, CaMKIV, and CREB.

"Our study aimed to investigate the effects of melatonin, ramelteon, and N1-acetyl-5-methoxyquinuramine on the relative phosphorylation levels of memory-related proteins in order to explore candidate signaling pathways associated with the receptor- and nonreceptor-mediated memory-enhancing effects of melatonin," explained Professor Chiba, of Sophia University's Department of Materials and Life Sciences, Faculty of Science and Technology.

Professor Chiba and associates conducted novel object recognition experiments in mice to confirm that melatonin, AMK or ramelteon promoted long-term memory formation. They subsequently determined that AMK or ramelteon increased phosphorylation levels of ERK and CREB and decreased phosphorylation of CaMKIIa and CaMKIIβ in the hippocampi of the animals' brains. In the perirhinal cortex of the brain which, like the hippocampus, is involved in memory, AMK and ramelteon increased the phosphorylation of ERK and ramelteon increased the phosphorylation of CaMKIIβ.

"Our findings suggest that melatonin is involved in promoting the formation of long-term object recognition memory by modulatinzxCXg the phosphorylation levels of memory-related proteins such as ERK, CaMKIIs, and CREB in both receptor-mediated and nonreceptor-mediated signaling pathways," Professor Chiba concluded.

—D Dye

CAR T cells eliminate senescent cells

August 18 2023. CAR T cell therapy is a type of cancer immunotherapy that involves engineering some of a patient's white blood cells known as T cells so that they produce chimeric antigen receptors (CARs). This enables these immune cells to recognize an antigen found on cancer cells. When the CAR T cells are infused back into the body, they attack and kill cancerous cells.

Research findings published on August 16 in Science Translational Medicine revealed another possible target for CAR T cells: senescent cells. These aged, dysfunctional cells cease to divide and remain in the body where they damage surrounding tissue and contribute to diseases and degenerative disorders. Elimination of senescent cells in mice has been associated with rejuvenation of aged tissues and extended lifespan.

Dong Yang of Sichuan University in China and colleagues discovered that senescent cells have high amounts of proteins known as NKG2DLs. By engineering T cells to target human NKG2DLs, NKG2D-CAR T cells eliminated cultured human cells that were induced to enter senescence by various factors. In irradiated and aged mice, mouse NKG2D-CAR T cells reduced the number of senescent cells in liver, lung and muscle tissue. NKG2D-CAR T cells also eliminated senescent cells in aged macaques, a type of nonhuman primate.

"Clearance of senescent cells may ameliorate age- and chronic disease-associated disorders," Yang and associates wrote. "Accumulating evidence suggests that improvements of existing senolytics, particularly in selectivity, are possible through immunotherapy."

"T cells armed with the human NKG2D CAR effectively delete naturally occurring senescent cells in aged nonhuman primates without any observed adverse effects," they concluded. "Our findings establish that NKG2D-CAR T cells could serve as potent and selective senolytic agents for aging and age-associated diseases driven by senescence."

—D Dye

Vegetable nutrients lower in Alzheimer brains

August 16 2023. Research reported this year in the Journal of Alzheimer's Disease revealed that levels of vitamin E and plant pigments known as carotenoids in the brains of people with Alzheimer disease were approximately half of those of levels found in normal brains.

First author C. Kathleen Dorey, who is professor at Virginia Tech Carilion School of Medicine, along with colleague Neal E. Craft, had previously discovered that the brain selectively accumulated carotenoids. Following their discovery, other research revealed a lower risk of dementia among people with greater intake of lutein and zeaxanthin compared to those with lower intake.

"This study, for the first time, demonstrates deficits in important dietary antioxidants in Alzheimer's brains," Dr Dorey announced. "These results are consistent with large population studies that found risk for Alzheimer's disease was significantly lower in those who ate diets rich in carotenoids, or had high levels of lutein and zeaxanthin in their blood, or accumulated in their retina as macular pigment. Not only that, but we believe eating carotenoid-rich diets will help keep brains in top condition at all ages."

The researchers compared micronutrient levels in brains donated by individuals who had died with Alzheimer disease and in brains donated by healthy older people. They found that gray and white matter from brains affected by Alzheimer disease had significantly lower levels of retinol (vitamin A), the carotenoids lutein, zeaxanthin, anhydrolutein, lycopene, and the alpha-tocopherol form of vitamin E compared to age-matched healthy brains.

"Recent advances in new therapies for Alzheimer's disease show exciting promise as an effective way to slow disease progression," Dr Dorey stated. "I'd be thrilled if our data motivated people to keep their brains in optimum condition with a colorful diet with abundant carotenoids and regular exercise. Available studies suggest this may also reduce risk for dementia."

—D Dye

Vitamin D intake and vitamin D levels associated with decreased insulin resistance among diabetics

August 14 2023. Findings from a meta‑analysis and systematic review published July 31, 2023, in the Nature journal Scientific Reports add evidence to an association between higher serum vitamin D levels or treatment with vitamin D and improved insulin, glucose and insulin resistance in people with type 2 diabetes.

Noting that causality is not established by observational studies, authors Xingxing Lei and colleagues explained that the current research also included randomized controlled trials in the hope of more precisely defining the relationship between vitamin D and insulin resistance. They selected 18 trials that compared insulin, glucose and insulin resistance among participants who received vitamin D with those who received a placebo and 20 observational studies that evaluated the association between serum vitamin D levels and these effects. The trials included a total of 1,243 participants and the observational studies included 11,063 participants.

Meta-analysis of the randomized trials revealed significantly improved serum insulin levels, blood glucose and HOMA-IR (which evaluates insulin resistance) among participants who received orally administered vitamin D in comparison with participants who received only standard diabetes therapy. Additionally, meta-analysis of the observational studies affirmed an association between higher vitamin D levels and lower insulin, glucose and insulin resistance. Lei and associates speculated that vitamin D deficiency is a key factor that accelerates the development of insulin resistance and elevated blood glucose.

"Results of overall analysis proved that vitamin D has shown significant effect on regulating insulin resistance, and there is a significant inverse association between serum vitamin D level and insulin resistance," they concluded. "Vitamin D supplementation is expected to be integrated into conventional medical approaches to prevent type 2 diabetes and to mitigate the burden of diabetes for individuals and society."

—D Dye

Low vitamin K linked with reduced lung function

August 11 2023. A study reported on August 10, 2023, in ERJ Open Research revealed reduced vitamin K among individuals with poor lung function or lung disease.

"We already know that vitamin K has an important role in the blood and research is beginning to show that it's also important in heart and bone health, but there's been very little research looking at vitamin K and the lungs," first author Torkil Jespersen observed. "To our knowledge, this is the first study on vitamin K and lung function in a large general population. Our results suggest that vitamin K could play a part in keeping our lungs healthy."

The investigation included 4,066 men and women between the ages of 24 and 77 years enrolled in the Danish study of Functional Disorders. Responses to questionnaires completed by the participants provided information concerning general health, chronic diseases and lifestyle. Examinations conducted from 2017 to 2020 included evaluation of lung function with spirometry and assessed urine and blood values, including plasma dp-ucMGP, which is elevated when vitamin K is low and used as a marker of low vitamin K status.

Participants with lower vitamin K had poorer lung function (as indicated by diminished forced expiratory volume and forced vital capacity measurements) than those with higher vitamin K status. Those with lower vitamin K had more than twice the adjusted risk of chronic obstructive lung disease (COPD), a 40% greater risk of wheezing and a 29%–32% higher risk of asthma than those with higher vitamin K.

"This study suggests that people with low levels of vitamin K in their blood may have poorer lung function," Apostolos Bossios of the Karolinska Institutet commented. "Further research will help us understand more about this link and see whether increasing vitamin K can improve lung function or not."

—D Dye

Does aging exist?

August 09 2023. In a research perspective published on July 20, 2023, in Aging, Mikhail V. Blagosklonny, PhD, MD, of Roswell Park Comprehensive Cancer Center discussed the use of the mechanistic target of rapamycin kinase (mTOR) inhibitor rapamycin as a pro-longevity drug and explained the hypothesis that aging, while seemingly programmed, is not programmed in actuality. He considers aging to be the sum of treatable aging-related diseases and prediseases, not as a real, uniform process.

"Aging is not programmed but, in contrast, quasi-programmed," he explained. "Quasi means pseudo; seemingly; apparently but not really." He added that quasi-programs are driven by hyperfunctional cells, signaling pathways and systems, such as the senescence-associated secretory phenotype and pro-inflammation. According to Dr Blagosklonny, the hyperfunction theory of quasi-programmed diseases challenges the need for the traditional concept of aging.

Dr Blagosklonny observed that rapamycin is the only drug that has extended life span in all species in which it was evaluated. "These results had been predicted by hyperfunction theory of quasi-programmed aging, which presents rapamycin as a universal anti-aging drug that suppresses cellular senescence and organismal aging, and thus decelerates development of age-related diseases, deadly manifestations of aging," he wrote. "Aging is driven in part by hyperfunctional growth-promoting pathways such as mTOR."

Rapamycin was originally developed as an immunosuppressant to lower the risk of organ rejection in transplant patients. Yet at doses used to treat aging, the drug eliminates hyperimmunity rather than suppresses immunity. Although mTOR regulates processes needed for cell growth and metabolism, it can render cells hypertrophic and hyperfunctional, leading to the development of aging-associated conditions and diseases. These quasi-programmed diseases are partly the result of a continuation of mTOR-driven cellular growth.

To boost longevity, Dr Blagosklonny recommended concentrating on potentially life-limiting diseases and designing doses and schedules for treatments such as rapamycin and other drugs.

—D Dye

Umbrella review affirms vitamin E benefit in NAFLD

August 07 2023. Findings from an umbrella review published July 28, 2023, in the Journal of Digestive Diseases added further evidence to beneficial effects for vitamin E in nonalcoholic fatty liver disease (NAFLD), which describes liver conditions that occur among individuals who consume little to no alcohol. The disease is characterized by the accumulation of fat in the liver and is often seen among people who are obese.

"We conducted the present umbrella meta-analysis of randomized controlled trials to clarify the effects of vitamin E administration on alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), steatosis levels and fibrosis score in individuals diagnosed with NAFLD," Mingyue Wang of Nantong University and colleagues wrote. "To our knowledge, this is the first umbrella meta-analysis of randomized controlled trials to investigate this research question."

The umbrella review included six meta-analyses of randomized trials that compared the effects of vitamin E to a control among a total of 2,430 people with NAFLD. Participants were males and females between the ages of 4 to 75 years. The review affirmed that consuming vitamin E was associated with significant reductions in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), fibrosis scores and steatosis (fat) levels. Further analysis found a greater decrease in fibrosis scores when the dose of vitamin E was higher than 500 international units (IU) per day and when the duration of treatment with the vitamin was more than 20 months.

Wang and colleagues remarked that, according to the 2018 American Association for the Study of Liver Diseases practice guidelines, 800 IU vitamin E per day was associated with improvement of nonalcoholic steatohepatitis (NASH, to which NAFLD can progress) among nondiabetic individuals.

"Vitamin E administration reduces ALT, AST, fibrosis and steatosis levels in NAFLD subjects," they concluded.

—D Dye

Higher DHA levels associated with lower hearing loss risk

August 04 2023. A study reported on July 24, 2023, during the annual meeting of the American Society for Nutrition revealed a relationship between higher plasma levels of the omega-3 fatty acid docosahexaenoic acid (DHA) and a lower risk of hearing loss.

American Society for Nutrition Fellow Michael I. McBurney, PhD, and colleagues evaluated data from up to 115,303 participants in the UK Biobank, which obtained information from 502,639 men and women between the ages of 40 and 69 from 2007 to 2010. Information was available from 115,303 participants concerning whether they had difficulty hearing, from 113,134 respondents concerning if they had difficulty following a conversation if there is background noise and from 71,368 regarding hearing aid use. Plasma DHA was assessed as the percentage of total plasma fatty acids.

Individuals whose plasma DHA was among the top 20% of individuals in the study had an 8% to 20% lower risk of reporting hearing issues than those whose DHA was among the lowest 20%.

"Higher DHA levels have previously been found to be associated with a lower risk of heart disease, cognitive impairment, and death," stated Dr McBurney, who is a senior scientist at the Fatty Acid Research Institute and an adjunct professor in the Department of Human Health & Nutritional Sciences at the University of Guelph and the Friedman School of Nutrition Science and Policy at Tufts University. "Our study extends these findings to suggest a role for DHA in maintaining auditory function and helping reduce the risk of age-related hearing loss."

"Fatty fish and omega-3 supplements are both good dietary sources," he added. "If choosing to use a dietary supplement, compare products by reading the Supplement Facts panel for eicosapentaenoic acid (EPA) + DHA content."

—D Dye

More on olive oil and Alzheimer disease

August 02 2023. A study published on July 7, 2023, in Human Genomics identified the phytochemicals occurring in extra virgin olive oil that are likeliest to be active against Alzheimer disease.

Health benefits associated with the intake of a Mediterranean diet have been attributed, in part, to olive oil consumption. Studies have revealed benefits for the intake of olive oil in Alzheimer disease patients. Nevertheless, the plant compounds in olive oil that are responsible for cognitive benefits had not been previously ascertained.

A team of investigators combined artificial intelligence with other research techniques to analyze how bioactive compounds in extra virgin olive interact with Alzheimer disease pathways. "We hypothesize that a successful prevention or treatment strategy for Alzheimer disease should focus on the modulation of multiple biochemical networks involved in its pathogenesis including amyloid beta production and aggregation, tau hyperphosphorylation, and neuroinflammation," Luís Rita and colleagues wrote.

Compounds that had the greatest probability of similarity to those being evaluated for the treatment of Alzheimer disease in FDA trials were considered likeliest of being active against the disease. The olive oil compounds quercetin, genistein, luteolin, palmitoleate, stearic acid, apigenin, epicatechin, kaempferol, squalene and daidzein were identified as most likely to interact with genes and proteins associated with Alzheimer disease pathology.

"The analyses identified several individual extra virgin olive oil phytochemicals that have a high likelihood of interfering with Alzheimer disease, a few of which (e.g., quercetin, genistein) have shown promising effects on Alzheimer disease pathogenesis," the authors concluded. "While the results of the present study shed light on how extra virgin olive oil may help treat or prevent Alzheimer disease, the same approach may be applied to identify extra virgin olive oil phytochemicals (or other food constituents) that treat other diseases, such as hypertension or dyslipidemia."

—D Dye

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