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.
How zinc helps fight esophageal cancer
September 29 2017. On September 19, 2017, the journal of the Federation of American Societies for Experimental Biology (The FASEB Journal) published the findings of research that explored the ability of zinc to inhibit the growth of esophageal cancer.
While zinc reduced the proliferation of esophageal squamous cell carcinoma lines, the effect was found to be reversible with the administration of a zinc chelator. Normal esophageal epithelial cells were significantly less sensitive to treatment with zinc. "Previously we didn't know why the same physiological concentrations of zinc inhibit cancer cell growth but not normal cells,” noted lead researcher Zui Pan, who is an associate professor of nursing at the University of Texas at Arlington’s College of Nursing and Health Innovation. “Our study, for the first time to our knowledge, reveals that zinc impedes overactive calcium signals in cancer cells, which is absent in normal cells, and thus zinc selectively inhibits cancer cell growth. It now appears that zinc and calcium can have a cross talk, meaning that they can be linked."
"Zinc deficiency has been found in many cancer patients," Dr Pan added. "Both clinical data and animal studies have shown that this mineral is very important for overall body health and for cancer prevention . . . That's why it is important to have a good diet."
In regard to the current study, Anne Bavier, who is the dean of University of Texas at Arlington's College of Nursing and Health Innovation, commented that "It re-affirms UTA's position as a major player in the global battle against cancer. Zui's work on esophageal cancer gets straight to the heart our goal at the College of Nursing and Health Innovation to help solve health problems to build a healthier world."
Higher vitamin D levels associated with less severe disease in NAFLD patients
September 27 2017. The September 2017 issue of the Journal of Clinical and Translational Hepatology published the findings of researchers at Rutgers New Jersey Medical School of a lower amount of liver steatosis (fat) and fibrosis and a decreased risk of mortality over a 19 year median among individuals with nonalcoholic fatty liver disease (NAFLD) who had higher vitamin D levels.
“To our knowledge, this is the first study to report vitamin D’s prognostic role in NAFLD,” authors Hun-Seok Kim and colleagues announce.
The study included 10,960 men and women enrolled in the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988-1994. Follow-up mortality data was collected through 2011. Ultrasound imaging of the liver revealed mild, moderate or severe NAFLD in 4,015 subjects. Deficient serum 25-hydroxyvitamin D levels were uncovered in 4,991 subjects.
Increasing vitamin D levels were associated with decreasing liver steatosis severity. Additionally, liver fibrosis was lowest among those whose vitamin D levels were highest. Among those with deficient levels of the vitamin, the risk of dying from diabetes was more than three and a half times greater than that of nondeficient subjects and for Alzheimer’s disease, the risk was over four and a half times greater. All-cause mortality risk was 16% higher among subjects with vitamin D deficiency compared with those whose levels were not deficient.
“Only a long-term follow-up study or clinical trials in NAFLD patients with vitamin D supplements will disclose the true effect of vitamin D in NAFLD pathogenesis,” the authors remark. “Thus, further investigation is warranted to disclose a more concrete causal pathway between vitamin D and other risk factors in the pathogenesis of NAFLD.”
Supplement users have lower metabolic syndrome risk
September 25 2017. A study reported on September 22, 2017 in Nutrients found a lower incidence of metabolic syndrome among dietary supplement users in Korea. Metabolic syndrome, a cluster of symptoms that include elevations in blood pressure, glucose and triglycerides, low HDL cholesterol levels, and abdominal obesity, is associated with an increased risk of diabetes and cardiovascular disease.
The study included 1,847 supplement users and 4,461 nonusers enrolled in the 2010-2011 Korea National Health and Nutrition Examination Survey. Twenty-four-hour diet recall data was analyzed for antioxidant content. Survey responses provided information concerning the use of supplements. Metabolic syndrome was diagnosed when three or more risk factors were present during health examinations.
There was a 18% lower prevalence of metabolic syndrome in dietary supplement users. Among those whose intake of vitamin A was among the highest one-third of supplement users there was a 28% lower risk of metabolic syndrome compared to nonusers whose intake of the vitamin was among the lowest third. For supplement users whose vitamin E was among the highest, the risk was 26% lower. Supplement users whose total antioxidant capacity from diet and supplements was among the top third of subjects had a 28% lower risk of metabolic syndrome than nonusers whose total antioxidant capacity was among the lowest.
“In conclusion, 30.8% of antioxidants and 38% of total antioxidant capacity were supplied on average by dietary supplements, suggesting that dietary supplements are quite important sources of antioxidant intake and TAC among Korean adults,” Subeen Kim and colleagues conclude. “A more comprehensive investigation of dietary supplements to clarify the effects on metabolic syndrome is necessary.”
New antioxidant protects neurons
September 22 2017. Research involving a potent antioxidant, described on September 19, 2017 in Scientific Reports, suggests that the compound could help protect cells in several conditions, including Parkinson’s disease, multiple sclerosis and cell transplants.
In their report, a team from the University of Edinburgh observe that the flavonoids quercetin and myricetin are among the most potent dietary antioxidants. Structural modification of myricetin has resulted in the development a new compound known as Proxison. In the current research, Proxison demonstrated 10 times the ability to protect against oxidative stress induced by the compound tert-Butyl hydroperoxide (tBHP) in neuroblastoma cells compared to quercetin, while several other antioxidants showed no effects. Proxison, as well as a high concentration of quercetin, also provided significant protection against cell death in tBHP-treated cells. Similar results were obtained in another neural cell line.
An investigation of the antioxidants’ ability to be taken up by the cells showed significant intracellular levels of quercetin and Proxison, and evidence for some localization of Proxison in the cells’ mitochondria.
In zebrafish embryos, Proxison helped protect against neuronal cell loss induced by a neurotoxic compound. Quercetin was also protective, but was less potent than Proxison. Neither therapy affected normal embryonic development.
“This novel antioxidant can be applied to investigate oxidative stress in disease models, like alpha-synucleinopathies and other neurodegeneration models,” Nicola J. Drummond and colleagues conclude. “In addition, Proxison could have applications for regenerative medicine where oxidative stress has been implicated in poor cell survival of transplanted cells, with the advantage that the molecule can be pre-loaded into cells prior to transplantation. Proxison could also have applications for conditions, such as stroke or cardiac infarction, in which a temporary, but acute, exposure to oxidative stress is experienced, as well as diseases in which oxidative stress and mitochondrial dysfunction are core features.”
“Aging is an evolutionary oversight”
September 20 2017. In an article published on September 7, 2017 in Genes & Development, researchers at Germany’s Institute of Molecular Biology revealed evidence in support of a hypothesis of aging presented in 1953. In that year, George C. Williams proposed that natural selection favors genes that promote reproductive success regardless of whether they negatively impact longevity when such negative effects occur after the onset of reproduction—a hypothesis known as antagonistic pleiotropy.
The current research adds support to the hypothesis by providing genetic evidence. "The evolutionary theory of aging just explains everything so nicely but it lacked real evidence that it was happening in nature,” stated co-author Jonathan Byrne. “Evolution becomes blind to the effects of mutations that promote aging as long as those effects only kick in after reproduction has started. Really, aging is an evolutionary oversight."
"These antagonistic pleiotropy genes haven't been found before because it's incredibly difficult to work with already old animals, we were the first to figure out how to do this on a large scale," he continued. "From a relatively small screen, we found a surprisingly large number of genes that seem to operate in an antagonistic fashion."
Autophagy is a process that occurs within the cell by which its components are degraded and recycled. "We found a series of genes involved in regulating autophagy, which accelerate the aging process," revealed lead researcher Holger Richly. "Autophagy is nearly always thought of as beneficial even if it's barely working. We instead show that there are severe negative consequences when it breaks down and then you are better off bypassing it all together. In young worms, autophagy is working properly and is essential to reach maturity but after reproduction, it starts to malfunction causing the worms to age."
Inactivation of genes involved in initiating autophagy in the neurons of old worms resulted in a longer health span and life span. "Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age who you then live longer than, that's what it's like for the worms," remarked co-author Thomas Wilhelm. "We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms and we think this is what keeps the muscles and the rest of the body in good shape. The net result is a 50% extension of life."
"There are many neuronal diseases associated with dysfunctional autophagy such as Alzheimer's, Parkinson's, and Huntington's disease, it is possible that these autophagy genes could represent a good way to help preserve neuronal integrity in these cases," Dr Wilhelm added.
How calorie restriction works
September 18 2017. In an article published on September 14, 2017 in Nature Communications, Temple University researchers reveal an explanation for the life extending effect of calorie restriction. Jean-Pierre J. Isaa, MD, and colleagues discovered that restricting the amount of calories consumed slows the aging-related rate of change of the epigenome, which consists of proteins and other compounds that can attach to DNA and control its action. The team is also the first to demonstrate that the rate of epigenomic change is associated with lifespan.
"Our study shows that epigenetic drift, which is characterized by gains and losses in DNA methylation in the genome over time, occurs more rapidly in mice than in monkeys and more rapidly in monkeys than in humans," explained Dr Issa, of the Fels Institute for Cancer Research at Temple’s Lewis Katz School of Medicine. "Our next question was whether epigenetic drift could be altered to increase lifespan.”
After studying age-related DNA methylation, Dr Issa and colleagues compared the age-related epigenetic drift of 22 to 30-year-old rhesus monkeys that received calorie restricted diets beginning at 7 to 14 years of age to a group of monkeys that were fed non-restricted diets. They found that the calorie restricted animals’ blood methylation age was 7 years less than their chronologic age. Similar effects were observed in older mice that were fed restricted diets.
"The impacts of calorie restriction on lifespan have been known for decades, but thanks to modern quantitative techniques, we are able to show for the first time a striking slowing down of epigenetic drift as lifespan increases," Dr Issa stated. "Our lab was the first to propose the idea of modifying epigenetic drift as a way of modifying disease risk. But why epigenetic drift occurs faster in some people and slower in others is still unclear."
Is calorie restriction a diabetes cure?
September 15 2017. Research reported at the European Association for the Study of Diabetes (EASD 2017) annual meeting, held September 11-15, 2017, adds evidence to the hypothesis that type 2 diabetes is caused by excess fat in the pancreas and liver, which can be eliminated by consuming a low calorie diet.
Professor Roy Taylor presented an overview of decades of research that led to his Twin Cycle Hypothesis. He asserts that fatty liver caused by the intake of excess calories results in poor response of the organ to insulin and increased glucose production. Excess liver fat increases the export of fat to all tissues, including the pancreas, where it negatively impacts insulin-producing cells. By consuming fewer calories, fat loss occurs in the pancreas, which can normalize insulin production and reverse type 2 diabetes.
A study published in Diabetologia documented a reduction in liver fat and normalization of insulin sensitivity in the livers of diabetics a week after the initiation of a low calorie diet. After 8 weeks, pancreatic fat content subsequently declined and first phase insulin secretion became normalized.
"I think the real importance of this work is for the patients themselves," Professor Taylor remarked. "Many have described to me how embarking on the low calorie diet has been the only option to prevent what they thought - or had been told - was an inevitable decline into further medication and further ill health because of their diabetes. By studying the underlying mechanisms, we have been able to demonstrate the simplicity of type 2 diabetes."
"The good news for people with type 2 diabetes is that our work shows that even if you have had the condition for 10 years, you are likely to be able to reverse it by moving that all important tiny amount of fat out of the pancreas,” he added.
Antioxidant treatment could halt neurodegeneration in early Parkinson’s
In human neurons derived from Parkinson’s disease patients, Dimitri Krainc and colleagues at Northwestern University identified a cascade that begins with mitochondrial oxidant stress leading to oxidized dopamine accumulation. This, in turn, results in a reduction in the activity of an enzyme known as lysosomal glucocerebrosidase, which weakens the function of the cells’ lysosomes: organelles within the cell that contain over 60 different enzymes. The cascade also results in the accumulation of alpha-synuclein, a protein that aggregates in the neurons of those with Parkinson’s disease. "The mitochondrial and lysosomal pathways are two critical pathways in disease development," explained Dr Krainc, who is the the Aaron Montgomery Ward Professor and chair of neurology at Northwestern University Feinberg School of Medicine. "Combined with the alpha-synuclein accumulation, this study links the major pathological features of Parkinson’s disease."
The researchers found that treatment with two different antioxidants, including N-acetylcysteine (NAC), interrupted the cascade. "One of the key strategies that worked in our experiments is to treat dopamine neurons early in the toxic cascade with specific antioxidants that improve mitochondrial oxidant stress and lower oxidized dopamine," Dr Krainc stated. "With this approach, we found that we can attenuate or prevent the downstream toxic effects in human dopaminergic neurons."
“Our long-term midbrain cultures demonstrated that early treatment with mitochondrial antioxidants reduced downstream accumulation of oxidized dopamine and alpha-synuclein, and rescued lysosomal dysfunction, highlighting the importance of early therapeutic intervention in the pathogenic cascade,” the authors conclude.
Hormone therapy not linked with premature mortality
September 11 2017. An article published on September 12, 2017 in the Journal of the American Medical Association (JAMA) concluded that hormone replacement therapy (HRT) prescribed to women for menopausal complaints had no association with a greater risk of death from cardiovascular disease or any cause over an 18 year period. The study is the first to examine long-term rates of death among women receiving HRT.
Researchers from Brigham and Women's Hospital examined data from 27,347 women enrolled in the Women’s Health Initiative trials that evaluated the effects of estrogen plus progestin, or estrogen alone in postmenopausal women. The trials included 5 to 7 years of treatment and a subsequent 10-12 years of follow-up.
Over the follow-up period, there were 7,489 deaths, which was twice the number documented in earlier reports with shorter follow-up times. Younger women who received HRT had fewer deaths in comparison with older participants who received treatment. Among women aged 50-59 years who received HRT, death rates averaged 30% lower than a placebo during the treatment period. Hormone replacement therapy had no association with mortality among women who initiated treatment in their 60s and 70s. At 18 years, deaths associated with dementia were lower in the group treated with estrogen only than those who received a placebo.
"In this new analysis, we found that there was no association between hormone therapy and all-cause mortality during either the treatment period or the long-term follow-up of these trials," reported lead author JoAnn Manson, MD, DrPH, who is the Chief of Brigham and Women’s Hospital’s Division of Preventive Medicine.
"All-cause mortality provides a critically important summary measure for an intervention such as hormone therapy that has a complex matrix of benefits and risks," she noted. "Mortality rates are the ultimate 'bottom line' when assessing the net effect of a medication on serious and life-threatening health outcomes."
Lowering inflammation reduces cancer, heart risk
September 8 2017. Results from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) Trial, reported on August 27, 2017 in the New England Journal of Medicine, show a lower risk of cardiovascular events among subjects who received canakinumab in comparison with a placebo. A separate report, published in The Lancet, documented a reduction in lung cancer incidence and mortality among subjects treated with the drug. Canakinumab inhibits the signaling of interleukin-1 beta, a cytokine associated with inflammation.
The trial enrolled 10,061 participants between April 2011 and March 2014. Subjects included men and women with a history of heart attack and high levels of C-reactive protein (CRP, a marker of inflammation). Participants received 50 mg, 150 mg, or 300 mg canakinumab, or a placebo through June 2017.
After two years, CRP was reduced among participants who received canakinumab, while lipid levels remained the same. At a median follow-up of 3.7 years, participants who received 150 mg canukinumab had a significant reduction of 15% in the risk of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Lung cancer incidence and mortality were also lower among those who received canakinumab.
“These findings represent the end game of more than two decades of research, stemming from a critical observation that half of heart attacks occur in people who do not have high cholesterol," stated principal investigator Paul M. Ridker, MD. "For the first time, we've been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk."
"As an inflammatory biologist and cardiologist, my primary interest is heart disease but CANTOS was a good setting to explore a previously observed link between cancer and inflammation," Dr Ridker added. "The data on cancer rates point to the possibility of slowing the progression of certain cancers, but these are exploratory findings that need replication."
Mayo Clinic: senolytic drugs could be transformative
September 6 2017. In a review published on September 4, 2017 in the Journal of the American Geriatrics Society, researchers from the Mayo Clinic predicted that senolytic drugs that are the subject of experimental research have the potential to transform the treatment of disease by preventing or delaying chronic conditions as a group, rather than one at a time.
Senolytic agents target senescent cells, which have stopped dividing and release compounds that damage nearby cells. Senescent cell accumulation is associated with arthritis, cardiovascular disease, cancer, dementia, frailty and diabetes.
Recent research conducted by the Mayo Clinic, along with the Scripps Research Institute, confirmed that senolytic drugs clear senescent cells without affecting normal cells. A new screening platform and human cell assays identified and confirmed a novel category of these drugs, which are known as heat shock protein 90 (HSP90) inhibitors. The research was reported in Nature Communications.
"We've moved rapidly in the last few years, and it's increasingly looking like senolytic drugs, including the recently discovered HSP90 inhibitors, are having an impact on a huge range of diseases,” commented James Kirkland, MD, PhD, who is the director of the Mayo Clinic's Robert and Arlene Kogod Center on Aging. “We will need to continue to test whether there are more optimal drugs or drug combinations to broaden the range of senescent cell types targeted."
"Our goal is to achieve the same success in humans as we have in preclinical animal models in efforts to prevent or delay the conditions associated with aging," Dr Kirkland added.
Having enough vitamin C could help suppress leukemia
The September 28, 2017 issue of the journal Nature describes research conducted at the University of Texas Southwestern Medical Center Children's Research Institute (CRI) that determined that hematopoietic (blood-forming) stem cells take up high levels of vitamin C which regulates their function and suppresses the development of leukemia.
Using mice that lacked an enzyme which enables most mammals to synthesize their own vitamin C, the researchers gave the animals diets that contained depleted levels of the vitamin. Rather than the anticipated loss of stem cell function, a gain in function occurred, accompanied by an increased risk of leukemia.
"Stem cells use ascorbate to regulate the abundance of certain chemical modifications on DNA, which are part of the epigenome," explained lead author Michalis Agathocleous. "The epigenome is a set of mechanisms inside a cell that regulates which genes turn on and turn off."
The authors determined that vitamin C regulates hematopoietic stem cell function partly through mechanisms involving the enzyme Tet2 which, when mutated is inactivated early in the development of leukemia. "One of the most common mutations in patients with clonal hematopoiesis is a loss of one copy of Tet2,” noted corresponding author Sean Morrison, who is the Director of the CRI. “Our results suggest patients with clonal hematopoiesis and a Tet2 mutation should be particularly careful to get 100 percent of their daily vitamin C requirement. Because these patients only have one good copy of Tet2 left, they need to maximize the residual Tet2 tumor-suppressor activity to protect themselves from cancer."
"We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we haven't fully understood why,” he remarked. “Our research provides part of the explanation, at least for the blood-forming system."