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.
Meta-analysis links higher vitamin K levels to lower risk of mortality during follow-up
October 31, 2018. The results of a meta-analysis reported on October 22, 2018 in the European Journal of Preventive Cardiology found evidence for an association between an increase in a marker of vitamin K deficiency and a lower risk of dying from any cause or cardiovascular disease during up to 12 years of follow-up.
The meta-analysis included 11 prospective studies that involved a total of 33,289 subjects. Studies were restricted to those that provided data concerning cardiovascular health or all-cause mortality, and vitamin K intake or levels of desphospho-uncarboxylated matrix Gla protein (dp-ucMcP, a marker of vitamin K deficiency). “As compared with dietary vitamin K intake that is generally acquired from food-frequency questionnaires, dpucMGP is a more robust and simple marker for vitamin K status,” Shangshu Zhang and colleagues explain. “To the best of our knowledge, the present study is the ﬁrst meta-analysis in which the association between dp-ucMGP and the risk of cardiovascular events and mortality has been quantitatively assessed.”
When subjects with high levels of circulating dp-ucMGP were compared to those with low levels, higher dp-ucMGP was associated with a 70% greater risk of all-cause mortality and an 80% higher risk of cardiovascular disease mortality during follow-up.
“These ﬁndings highlight that high dp-ucMGP levels, indicative of vitamin K insuﬃciency, may serve as an independent predictor for the risk of mortality,” the authors conclude. “For further clariﬁcation of the role of dp-ucMGP in cardiovascular disease and mortality risk, more and larger-population studies are warranted.”
Rapamycin, diet modification associated with better neurovascular function
"Our earlier work already demonstrated the positive effect rapamycin and caloric restriction had on neurovascular function," commented lead researcher Ai-Ling Lin of the University of Kentucky. "We speculated that neuroimaging might allow us to see those changes in the living brain."
Rapamycin has been found to increase life span in various species by inhibiting a nutrient sensor known as mTOR. In the current research, imaging studies enabled the researchers to observe that rapamycin could protect against Alzheimer’s brain pathology in a mouse model of the disease.
In young mice, a calorie restricted diet resulted in greater cerebral blood flow compared to animals on non-restricted diets, while reducing mTOR. Calorie restriction also enhanced cerebral blood flow in older mice, resulting in animals whose cerebral blood flow levels were similar to that of young mice that did not receive restricted diets.
"Ai-Ling's lab was the first to use neuroimaging to see these changes in a living brain, and the potential link to changes in the gut microbiome," noted Linda Van Eldik, PhD, who is the Director of the UK Sanders-Brown Center on Aging. "Her work has tremendous implications for future clinical trials of neurological disorders in aging populations."
"We will use neuroimaging to identify the association between gut microbiome balance and brain vascular function in individuals over 50 years of age, with an ultimate goal to design and test nutritional and pharmacological interventions that will prevent Alzheimer's disease," Dr Lin stated.
Inhibition of enzyme boosts NAD+
October 26, 2018. An article that appeared on October 24, 2018 in Nature reports the discovery of a mechanism that increases the body’s level of nicotinamide adenine dinucleotide (NAD+). NAD+ is a coenzyme that assists many metabolic enzymes, which are involved in the production of energy. The decline of NAD+ concentrations during aging have made the coenzyme the focus of research that has explored ways to increase it.
A team led by Johan Auwerx of the Ecole Polytechnique Fédérale de Lausanne demonstrated that the enzyme ACMSD, which limits the amount of NAD+ produced from tryptophan within the cells, controls NAD+ levels via a mechanism shared by both worms and mice. Blocking ACMSD was associated with an elevation in NAD+, improved function of the cells’ mitochondria, and greater activity of the enzyme Sirtuin 1 (involved in mitochondrial health), for which NAD+ is a coenzyme.
When the researchers tested two inhibitors of ACMSD in animal models of acute kidney injury and nonalcoholic fatty liver disease, kidney and liver function were preserved. "Since the enzyme is mostly found in the kidney and liver, we wanted to test the capacity of the ACMSD inhibitors to protect these organs from injury," explained first author Elena Katsyuba. "The fact that ACMSD is exclusively present only in the liver and kidneys reduces the risk of negative repercussions of its loss on other organs. Put simply, the enzyme will not be missed by an organ that does not have it anyway."
"Given the beneficial health effects of boosting NAD+ levels that we have seen in worm and mouse models of disease, we are looking forward to bringing these compounds soon to the clinic to the benefit of patients suffering from liver and kidney diseases, two areas with a large unmet clinical need," Dr Auwerx concluded.
Drug combo extends life in roundworm
October 24, 2018. A combination of drugs might be used someday to extend human life, according to research reported on October 8, 2018 in Developmental Cell.
"If we can find a way to extend healthy lifespan and delay aging in people, we can counteract the detrimental effects of an aging population, providing countries not only medical and economic benefits, but also a better quality of life for their people,” predicted lead researcher Jan Gruber, of Yale NUS College in Singapore. "We would benefit not only from having longer lives, but also spend more of those years free from age-related diseases like arthritis, cardiovascular disease, cancer, or Alzheimer's disease."
Dr Gruber and colleagues evaluated different compounds in the roundworm C. elegans to determine whether lifespan extension could be enhanced by targeting of two or more mechanisms that included those involving the mitochondria, AMPK, mTOR, calorie restriction, and c-Jun N-terminal kinases (JNK). The team first confirmed the life-extending effects of the single compounds rapamycin, rifampicin, metformin, the potassium-channel blocker psora-4, the calorie restriction mimetic allantoin, torin-1, aspirin, manserin, loxapine succinate, juglone and cyclic AMP (cAMP). Of these compounds, rapamycin, rifampicin, metformin, psora-4 and allantoin were demonstrated to have consistent and reproducible lifespan benefits.
Subsequent research revealed two double- and two triple-drug combinations whose administration was associated with decreased biologic aging rate and synergistic average lifespan extension. The combinations included rifampicin plus rapamycin, rifampicin plus psora-4, and these two combinations with the addition of allantoin.
“The effect size of our best combination is comparable to that of the classical aging mutations and significantly exceeds that of any of the single drugs,” the authors write. “Our results suggest that targeting multiple distinct but interacting pathways within the gene-regulatory network of aging can result in synergistic benefits on aging and healthspan.”
Old age survival: an advancing front
October 22, 2018. An article that appeared on October 16, 2018 in the Proceedings of the National Academy of Sciences suggests that, contrary to some predictions, there may not be a fixed limit to human lifespan.
“Old-age mortality decline has driven recent lifespan increases, but there is no agreement about the age pattern of old-age deaths,” write Wenyun Zuo of Huazhong University of Science and Technology in China and colleagues. “For example, some argue that old-age deaths should become compressed at advanced ages, and others argue that old-age deaths should become more dispersed with age. Here we show, for five decades in 20 developed countries, that old-age survival follows an advancing front, like a traveling wave.”
The researchers analyzed annual life-tables for 20 countries in the Human Mortality Database for the years 1960-2010. They found that the front has advanced consistently during the five decades examined.
Among Dr Zuo and colleagues’ observations is that the definition of old age is changing. In Japan, for example, a woman had an approximately 80% chance of surviving past the age of 60 years in 1960, past the age of 70 in 1977, and past 80 in 2011. Correspondingly, the age at which individuals transition to disability has also been steadily increasing. This factor, along with increased economic growth and advances in health science research, are suggested as causes for the increasing delay in mortality.
“Our findings imply that we must welcome continued aging despite its challenges,” the authors conclude.
Omega 3-fatty acid EPA linked to healthy aging
October 19, 2018. An article appearing on October 17, 2018 in The BMJ concludes that having a higher level of the omega-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA), found in fish and seafood, is associated with a greater likelihood of healthy aging among older men and women. According to the authors, healthy aging is defined as survival without such chronic diseases as cardiovascular disease, cancer, lung disease, and severe chronic kidney disease, and the absence of physical and cognitive dysfunction after the age of 65.
“With rapid ageing of populations globally and an increased prevalence of chronic disease, focus on longevity alone is shifting toward an emphasis on healthy ageing,” Heidi T. M. Lai, PhD, and colleagues write. “In contrast with years of total life, healthy aging can be considered as living a meaningful lifespan without chronic diseases and with intact physical and mental function.”
The study included 2,622 older men and women enrolled in the US Cardiovascular Health study from 1992 to 2015. Annual clinical examinations conducted through 1999 and semiannual phone interviews ascertained health status and other factors. Blood samples collected at three time points were analyzed for the omega-3 fatty acids EPA, DHA, DPA and ALA.
Dr Lai and associates found that only 11% of the subjects experienced healthy aging during the course of the study. Among those whose EPA levels placed them among the top 20% of participants, the adjusted risk of unhealthy aging was 24% lower than the risk experienced by those whose levels were among the lowest 20%. Higher docosapentaenoic acid (DPA) levels also appeared to be protective. Participants whose DPA levels were among the top 60% had an 18-21% reduction in risk.
“These findings support guidelines for increased dietary consumption of omega-3-PUFAs in older adults,” the authors conclude.
Omega-3 shows promise in breast cancer
October 17, 2018. An article that appeared online on October 16, 2018 in the journal Clinical & Experimental Metastasis revealed the finding of researchers at the University of Nebraska of a potential benefit for omega-3 fatty acids in the treatment of breast cancer.
"Our study emphasizes the potential therapeutic role of dietary long-chain omega-3 fatty acids in the control of tumor growth and metastasis," stated lead author Saraswoti Khadge of the University of Nebraska Medical Center’s Department of Pathology and Microbiology.
The current research involved two groups of female mice that received diets which contained omega-3 fatty acids from fish oil or an equal amount of fat from omega-6 fatty acids (which are derived from plants) for 16 weeks. At the end of this period, the mice were injected with aggressive breast cancer cells. Animals that survived were autopsied 35 days later.
Mice that received omega-3 fatty acids failed to develop breast tumors or experienced delays in tumor development compared to animals that received omega-6. Additionally, tumors were 50% smaller on the 35th day following the injection of cancer cells among animals that received omega-3. Metastases to the heart, kidneys and ovaries were fewer and smaller in the omega-3 group.
Analysis of tumor microenvironment revealed that tumors in mice that received omega-3 had a greater number of cells undergoing apoptosis (programmed cell death), fewer proliferating tumor cells, less new blood vessel formation, and other positive effects.“Our data suggest that dietary long chain omega-3 fatty acids modulates the mammary tumor microenvironment, slowing tumor growth and reducing metastases to both common and less preferential organs resulting in prolonged survival,” Dr. Khadge and colleagues conclude.
Trial finds metformin improves cognitive function
October 15, 2018. Results from a trial reported this year in Frontiers in Aging Neuroscience reveal a benefit for the diabetes drug metformin in patients with abnormal glucose metabolism and nondementia vascular cognitive impairment.
“Recent studies have shown that metformin can rapidly penetrate the blood–brain barrier to protect neurons through anti-inflammatory processes and improvement of brain energy metabolism,” write researchers Yufeng Lin and colleagues at Tianjin Medical University in China. “Meanwhile, neuroimaging like magnetic resonance imaging and positron emission tomography have already proved that the neuroinflammation and brain metabolic stress may damage cognitive function.”
The trial included 100 participants who received donepezil (which is used to treat dementia) with metformin or acarbose (a drug that inhibits the enzyme alpha-glucosidase, thereby lowering glucose). Neuropsychologic status, glucose metabolism and common carotid artery intima-media thickness (which measures atherosclerosis) were evaluated at the beginning and end of the study.
Among participants who received metformin, cognitive function assessment and auditory verbal learning test scores were improved at the end of the study. In contrast, there was no improvement in cognitive function observed among those who received acarbose. Participants who received metformin experienced a significant decrease in fasting insulin levels and insulin resistance compared to pretreatment levels and to those in the acarbose group. And while those who received acarbose experienced an increase in common carotid artery intima media thickness after a year, those given metformin had no change.
“Impaired cognitive function in patients with nondementia vascular cognitive impairment and abnormal glucose metabolism is closely related to insulin resistance,” the authors conclude. “Treatment that combines metformin with donepezil can improve insulin resistance and reduce fasting insulin levels in such patients.”
They add that metformin could also contribute to cognitive function by helping to maintain healthy carotid arteries that supply blood to the brain.
Probiotic bacteria may help protect against staph infection
October 12, 2018. A study reported on October 10, 2018 in Nature suggests a protective role for the probiotic Bacillus subtilis against Staphylococcus aureus, a bacterium that can cause antibiotic-resistant infections, including methicillin-resistant Staphyllococcus aureus (MRSA) infections. Bacillus bacteria are commonly ingested along with vegetables, which allows the microorganisms to grow in the intestine.
By examining fecal samples from 200 healthy individuals residing in rural Thailand, Michael Otto of the National Institute of Allergy and Infectious Disease at the National Institutes of Health and colleagues discovered that the presence of Bacillus subtilus was associated with an absence of colonization of the nose and intestinal tract by S. aureus. The team found that a system in the body that senses S. aureus allows the bacteria to grow in the gut. All 101 Bacillus isolates obtained from fecal samples were shown to inhibit this system. It was determined that a class of lipopeptides known as fengycins in Bacillus subtilus were responsible for the inhibitory action and were effective against the strain that causes most MRSA infections in the United States. In mice whose intestinal tracts were colonized with S. aureus, the intake of B. subtilis spores every two days eliminated the harmful bacteria.
"Probiotics frequently are recommended as dietary supplements to improve digestive health," stated Anthony S. Fauci, MD, who is the Director of the National Institute of Allergy and Infectious Disease. "This is one of the first studies to describe precisely how they may work to provide health benefits. The possibility that oral Bacillus might be an effective alternative to antibiotic treatment for some conditions is scientifically intriguing and definitely worthy of further exploration."
"Ultimately, we hope to determine if a simple probiotic regimen can be used to reduce MRSA infection rates in hospitals," added Dr Otto.
Aspirin use linked to lower risk of liver cancer
Researchers at Massachusetts General Hospital analyzed data from 87,507 women who participated in the Nurses’ Health Study and 45,864 men who enrolled in the Health Professionals Follow-Up Study. The subjects’ use of aspirin was documented beginning in the 1980s. Regular aspirin use was defined as the intake of at least two standard-dose aspirins per week.
During more than 26 years of follow-up, 65 women and 43 men were diagnosed with hepatocellular carcinoma. In comparison with nonregular aspirin use, regular use was associated with a 49% lower risk the risk of disease. When duration of use was examined, the intake of at least 1.5 standard-dose aspirin tablets weekly for five or more years was associated with a 59% lower risk of HCC compared to no use. "Regular use of aspirin led to significantly lower risk of developing HCC, compared to infrequent or no aspirin use, and we also found that the risk declined progressively with increasing aspirin dose and duration of use," reported first author Tracey Simon, MD, of the Massachusetts General Hospital Division of Gastroenterology.
"The long duration of aspirin use could be necessary because primary liver cancer takes many years to grow,” Dr Simon suggested. “Aspirin may act at the earliest stages of cancer development, or even at precancerous stages, by delaying or preventing inflammation or liver fibrosis. While it's still too early know whether starting aspirin therapy might be an effective strategy to prevent HCC, efforts to understand the mechanisms behind these beneficial effects could help identify urgently-needed prevention strategies or biomarkers for a cancer that is a growing public health problem."
Vitamin D insufficiency associated with premature mortality risk among Thai men
October 8, 2018. A study reported on October 2, 2018 in the journal Geriatrics & Gerontology International reveals an increased risk of early mortality among Thai men who had low levels of vitamin D.
Authors Varalak Srinonprasert and colleagues observe that previous investigations concerning the association between vitamin D levels and survival have been conducted primarily in populations from high-income countries. The current study included 1,268 community-dwelling subjects between the ages of 67 to 81 years who enrolled in the Thai 4th National Health Examination Survey in 2008. Physical activity levels, the presence of diseases, and serum levels of 25-hydroxyvitamin D2 and D3 were assessed upon enrollment. Participants were followed until 2015.
Insufficient vitamin D levels were detected among 24.5% of the men and 43.9% of the women. At the study’s conclusion, men with vitamin D insufficiency had a 77% higher risk of dying from any cause during follow-up compared to those whose levels were sufficient. Among men whose 25-hydroxyvitamin D levels were among the lowest one-third of participants there was an 83% greater risk of premature mortality in comparison with those whose levels were among the top third. Having diabetes further increased the risk of early death in men with insufficient vitamin D levels. "Cardiovascular disease may be the link between vitamin D insufficiency and risk of death in diabetic older male," commented coauthor Dr. Chalermsri Chalobol, of Mahidol University, in Bangkok.“Low serum vitamin D is an independent risk factor for increased mortality in community‐dwelling Thai older men,” the authors concluded. “Further randomized controlled study to investigate the benefit of vitamin D3 supplementation in older persons, particularly men, is warranted.”
Fisetin extends lifespan in mice
October 5, 2018. An article that appeared on September 29, 2018 in the Lancet journal EBioMedicine reveals a role for fisetin, a flavonoid that occurs in strawberries, onions and other plant foods, in reducing the body’s level of senescent cells and extending life span.
Senescence describes an aging process in damaged cells that results in the release of signals that instruct the immune system to clear these cells. While the process is efficient in younger people, aging individuals are less able to clear senescent cells. Senescent cell accumulation results in inflammation and tissue damage.
Acting on an earlier finding of the possibility of lowering the burden of senescent cells in mice, thereby extending survival, Paul D. Robbins of the Scripps Research Institute and colleagues screened 10 flavonoids for senolytic activity in aged mouse and human cells. Fisetin proved to be the most potent. Dr Robbins and his associates observed that the chemical structure of fisetin is almost the same as that of quercetin which, when combined with the drug dasatinib, reduced senescent cells in the earlier research.
In old mice, supplementation with fisetin reduced age-related pathology in several tissues in comparison with animals that received an unsupplemented control diet. Fisetin also extended the animals’ average and maximum lifespan, which is the first time these effects have been observed in association with fisetin supplementation in vertebrates.
"These results suggest that we can extend the period of health, termed healthspan, even towards the end of life," Dr Robbins concluded. "But there are still many questions to address, including the right dosage, for example."
"In addition to showing that the drug works, this is the first demonstration that shows the effects of the drug on specific subsets of these damaged cells within a given tissue," he added.
B complex may protect against diabetic kidney disease
October 3, 2018. On September 28, 2018, the 57th Annual European Society for Paediatric Endocrinology Meeting was the site of a presentation of the finding a protective effect for B vitamin supplementation on the kidney function of children with type 1 diabetes. Kidney disease is a complication associated with diabetes that can require long-term treatment if not detected early.
"Although the best strategy for treating diabetic kidney disease is prevention, for example through better blood glucose control and maintenance of healthy blood pressure, a normal lipid profile and a healthy body weight, the long-term duration of diabetes still increases the risk of developing kidney disease,” noted researcher Nancy Samir Elbarbary of Ain Shams University in Cairo. “So, these findings suggest vitamin B supplementation, in addition to traditional angiotensin converting enzyme inhibitor therapy may be a simple, safe and cost-effective strategy for early protection of kidney function, which may improve the long-term quality of life for type-1 diabetes patients."
In the current study, 80 type 1 diabetics between the ages of 12 and 18 years with early signs of diabetic kidney disease and deficient levels of vitamin B12 were given vitamin B complex supplements or no treatment for 12 weeks. At the study’s conclusion, children who received B complex exhibited improvement in blood markers of glucose regulation and kidney function.
"After 12 weeks of vitamin B complex supplementation in children and adolescents with diabetic kidney disease, we detected lower levels of markers that indicate poor kidney function, suggesting that it had a protective effect and could slow progression of the disease," Dr Elbarbary reported. "These findings still need to be confirmed in larger, multi-center randomized trials to verify the role of vitamin B complex supplementation in treating early diabetic kidney disease over longer periods of time."
Free radicals blamed for toxic buildup in Alzheimer’s brains
October 1, 2018. A study reported in Cell Death & Disease revealed a previously unknown mechanism that may contribute to traumatic brain injury and Alzheimer’s disease. While a buildup of the protein amyloid-beta has been hypothesized to be the major driver of Alzheimer’s disease, the study suggests that another protein, after undergoing oxidation by free radicals, could be a causative factor.
"Indeed, scientists have known for a long time that during aging or in neurodegenerative disease cells produce free radicals," explained lead researcher Federico Sesti, who is a professor of neuroscience and cell biology at Rutgers Robert Wood Johnson Medical School. "Free radicals are toxic molecules that can cause a reaction that results in lost electrons in important cellular components, including the channels."
Dr Sesti and colleagues determined that oxidation of a potassium channel known as KCNB1 results in a toxic buildup of this protein, leading to increased amyloid-beta production and damage to brain function. "The discovery of KCNB1's oxidation/build-up was found through observation of both mouse and human brains, which is significant as most scientific studies do not usually go beyond observing animals," Dr Sesti reported. "Further, KCBB1 channels may not only contribute to Alzheimer's but also to other conditions of stress as it was found in a recent study that they are formed following brain trauma."
Acting on the knowledge that oxidation of KCNB1 channels in traumatic brain injury and Alzheimer’s disease leads to activation of Src tyrosine kinases, the researchers tested the effects of the Src kinase inhibitor dasatinib in a mouse model of Alzheimer's disease. "Our study shows that this drug and similar ones could potentially be used to treat Alzheimer's, a discovery that leads the way to launching a clinical trial to test this drug in humans," Dr Sesti concluded.