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.
Depression, stress may impact life span by altering gene expression
Acting on the finding of a longer life span in the roundworm C. elegans following the administration of the antidepressant mianserin, Alexander B. Niculescu III, MD, PhD, of the Indiana University School of Medicine and colleagues identified 231 genes whose activities were altered following exposure to the drug, which were subsequently correlated with 347 similar genes in humans. Using genome analysis data of 3,577 older humans, the researchers found an association between depression and 134 of these genes—particularly the gene ANK3, which increases with age in worms as well as in children with the rapid aging syndrome known as progeria. Evaluation of blood samples from suicide casualties and individuals diagnosed with psychiatric disorders uncovered an increase in ANK3 expression in these groups.
"We have found a series of genes involved in mood disorders and stress disorders which also seem to be involved in longevity," Dr Niculescu stated. "Our subsequent analyses of these genes found that they change in expression with age, and that people subject to significant stress and/or mood disorders, such as people who completed suicide, had a shift in expression levels of these genes that would be associated with premature aging and reduced longevity."
Further research identified compounds that may act on the genes identified in this study to promote longevity, including DHA, piracetam, quercetin, vitamin D, resveratrol, estrogenic compounds, antidiabetic drugs and rapamycin.
"These studies uncover ANK3 and other genes in our dataset as biological links between mood, stress and lifespan, that may be biomarkers for biological age as well as targets for personalized preventive or therapeutic interventions," the authors conclude.
Meta-analysis concludes protective effect for calcium supplementation against adenoma risk
May 23 2016. The May 14, 2016 issue of the World Journal of Gastroenterology published the results of a systematic review and meta-analysis of randomized trials that indicate a protective effect for calcium supplementation against the risk of colorectal adenoma, a precursor of colorectal cancer.
European researchers selected four trials that compared the effects of 1,200 to 2,000 milligrams elemental calcium per day to a placebo against the risk of colorectal adenoma during up to 60 months of treatment and follow-up. Subjects included men and women with resected colorectal cancer or those who had colorectal adenomas surgically removed prior to enrollment. Colonoscopic examinations conducted over the follow-up periods ascertained colorectal adenoma recurrence.
All of the trials reported a lower incidence of colorectal adenomas in the calcium group. The meta-analysis determined that subjects who received calcium experienced a 10% to 15% lower risk of adenoma recurrence compared with those who received the placebos.
The authors note that calcium may protect against colorectal neoplasia by binding bile and fatty acids, which reduces their carcinogenic effects on colon epithelial cells. Additionally, the mineral has a direct antiproliferative effect on cells and promotes cellular differentiation and apoptosis (programmed cell death).
Authors Stefanos Bonovas, MD, MSc, PhD and colleagues announce that the current study is the most up to date on the subject and that further clinical studies will help identify populations for whom calcium supplementation might be particularly beneficial for adenoma and cancer prevention.
"The magnitude of the colorectal cancer problem, and the failure of advanced disease chemotherapy to effect significant reductions in the respective mortality rates, indicate that an intensive approach to the prevention of this disease is necessary," they observe. "These findings extend the results of the primary trials and have important implications for future research."
Treatment of TIA with aspirin could help prevent major stroke
May 20 2016. An article appearing on May 18, 2016 in The Lancet suggests that the use of aspirin by individuals experiencing transient ischemic attack (TIA) could reduce the risk of experiencing a major ischemic stroke during the days following the event.
For the current study, Peter Rothwell and his associates evaluated data from the EXPRESS study conducted at the University of Oxford. "The risk of a major stroke is very high immediately after a TIA or a minor stroke (about 1000 times higher than the background rate), but only for a few days," Dr Rothwell observed. "We showed previously in the 'EXPRESS Study' that urgent medical treatment with a 'cocktail' of different drugs could reduce the one-week risk of stroke from about 10% to about 2%, but we didn't know which component of the 'cocktail' was most important."
"One of the treatments that we used was aspirin, but we know from other trials that the long-term benefit of aspirin in preventing stroke is relatively modest," he noted. "We suspected that the early benefit might be much greater. If so, taking aspirin as soon as possible after 'warning symptoms' event could be very worthwhile.'
It was discovered that aspirin's benefit primarily occurred during the first few weeks following a TIA and that the drug was associated with a 70 to 80% reduction in the early risk of fatal or disabling stroke in contrast with the 15% overall reduction in long term stroke risk uncovered by previous research.
"Our findings confirm the effectiveness of urgent treatment after TIA and minor stroke - and show that aspirin is the most important component," Dr Rothwell concluded. "This finding has implications for doctors, who should give aspirin immediately if a TIA or minor stroke is suspected, rather than waiting for specialist assessment and investigations."
Inflammation a likely culprit in GERD-related esophagitis
May 18 2016. A preliminary communication published on May 17, 2016 in the Journal of the American Medical Association implicates an inflammatory reaction triggered by the presence of stomach acid in the esophagus, rather than burns caused by the acid itself, as the damaging factor in patients with gastrointestinal reflux disease (GERD).
"Although this radical change in the concept of how acid reflux damages the esophagus of GERD patients will not change our approach to its treatment with acid-suppressing medications in the near future, it could have substantial long-term implications," remarked senior author Dr Stuart Spechler, who is a professor at the University of Texas Southwestern Medical Center and a physician at the VA Medical Center.
The current study included 12 patients being treated for GERD with proton pump inhibitors (PPIs) who were asked to discontinue their medication. Participants underwent esophageal biopsies at the beginning of the study and one and two weeks after stopping the drugs.
At one and two weeks, biopsies showed signs of T-lymphocyte-predominant inflammation. All subjects had evidence of esophageal acid exposure and esophagitis at two weeks, which is consistent with the time needed for damage caused by inflammation to develop. "These findings suggest that the pathogenesis of reflux esophagitis may be cytokine-mediated rather than the result of chemical injury," the authors conclude.
"A chemical burn should develop immediately, as it does if you spill battery acid on your hand," Dr Spechler noted.
Co-senior author Dr Rhonda Souza predicted that "Someday we might treat GERD with medications that target the cytokines or inflammatory cells that really cause the damage to the esophagus."
"We think that it is important for physicians to have an accurate understanding of the mechanisms underlying the diseases that we treat, especially one as common as GERD," Dr Spechler added.
Resveratrol combats effect of unhealthy diet on muscle
May 16 2016. An article published on March 2, 2016 in Frontiers in Physiology reveals a potential benefit for resveratrol in counteracting negative changes induced by a high fat, high sugar diet in muscle tissue.
"Skeletal muscle phenotype is determined, in part, by the type of myosin heavy chain (MHC) protein expressed throughout the tissue," explain Jon-Philippe K. Hyatt of Georgetown University and colleagues in their introduction. "The fiber types can be generally categorized from contractile speed and aerobic or anaerobic characteristics. Relative to fast muscles (with a preponderance of type II fibers), slow (type I) muscles are high in capillary density and mitochondrial volume, contain a greater proportion of aerobic enzymes, and are generally fatigue resistant."
Dr Hyatt's team gave 8 rhesus monkeys a diet that was high in fat and high in sugar for two years. Half of the group also received a daily placebo and the remainder received resveratrol over the course of the study. An additional four animals of the same age received a standard diet. Five young monkeys served as controls.
The soleus muscle of the lower hind leg was the most impacted by the high fat and sugar diet and also benefitted the most from resveratrol, which counteracted the diet-induced shift from slow to more fast. The plantaris muscle (also in the lower leg), while failing to be affected by the diet, also showed a shift to slower myosin in resveratrol-supplemented animals.
"The maintenance or addition of slow characteristics in soleus and plantaris muscles, respectively, implies that these muscles are far more fatigue resistant than those without resveratrol," Dr Hyatt commented. "Skeletal muscles that are phenotypically slower can sustain longer periods of activity and could contribute to improved physical activity, mobility, or stability, especially in elderly individuals."
Testosterone therapy associated with improved sexual function in diabetic men with severely low hormone levels
May 13 2016. An article appearing on May 27, 2016 in BJU International reveals better sexual function in men with type 2 diabetes with severely depressed hormone levels who were treated with testosterone undecanoate. Type 2 diabetes, as well as deficient testosterone levels, have been linked to a decline in sexual function in aging men.
The study included 189 men, among whom 107 had mild hypogonadism and 87 had severe hypogonadism as demonstrated by low total and free serum testosterone levels. Participants received 1,000 milligrams testosterone undecanoate or a placebo at the beginning of the study and at 6 and 18 weeks. Questionnaires that assessed erectile function, intercourse satisfaction, orgasmic function and desire were administered prior to treatment and at 6, 18 and 30 weeks.
After 30 weeks, significant improvement in erectile function in comparison with the period before treatment as well as in comparison with the placebo groups was noted by the severely deficient men treated with testosterone. Intercourse satisfaction and desire also improved at 6, 18 and 30 weeks in the severely deficient testosterone-treated group.
Authors Geoffrey Hackett of the Heart of England Foundation NHS Trust and colleagues conclude that men severely deficient testosterone levels who receive testosterone undecanoate therapy will probably see significant improvement in sexual function when treated for up to 30 weeks.
Dr Hackett noted that "The study's results also suggest that trials of testosterone therapy should be for a minimum of 6 months and not shorter periods as suggested by some guidelines."
Fasting helps reduce fatty liver
May 11 2016. Findings from an article published on March 5, 2016 in EMBO Molecular Medicine suggest that periodic fasting could help reduce fatty liver, a condition associated with obesity and type 2 diabetes.
"A hallmark of obesity‐driven type 2 diabetes is insulin resistance, and thus, much effort is placed into treatments that promote 'insulin sensitisation," Dr Stephan Herzig and colleagues write. "While there is no doubt that insulin is an important mediator of metabolic control in the prandial state, insulin resistance likely represents a physiological feedback mechanism to actually retard the development of obesity‐driven complications, prompting speculation that 'insulin sensitisation' may be a flawed strategy. This is exemplified by studies demonstrating that tissue‐restricted loss of function of key insulin signaling nodes actually extends health span of mice and that insulin per se can promote the progression of obesity‐related metabolic dysfunction."
In their search for alternative strategies to treat type 2 diabetes and its consequences, Dr Herzig's team studied the effects of fasting in a mouse model of obesity. By examining liver cell gene activity differences, the team demonstrated that the gene for the protein GADD45 beta (growth arrest and DNA damage-inducible) was more frequently expressed during hunger. They discovered that GADD45 beta is responsible for the control of fatty acid absorption in the liver and that mice lacking the gene had a higher risk of developing fatty liver disease.
In humans, low GADD45 beta levels were found to be associated with increased liver fat accumulation and elevated glucose. "The stress on the liver cells caused by fasting consequently appears to stimulate GADD45β production, which then adjusts the metabolism to the low food intake," Dr Herzig reported.
"Our findings demonstrate the importance of fasting hepatic lipid metabolism in systemic metabolic control and provide insight into the development of new therapies for metabolic dysfunction," the authors conclude.
Testosterone therapy associated with lower risk of aggressive prostate cancer
May 9 2016. The results of a recent analysis of 231,408 medical records has failed to find an association between testosterone replacement therapy and an increased risk of prostate cancer, and furthermore determined that the therapy appears to be associated with a lower risk of aggressive disease. The findings, presented on May 9, 2016 at the American Urological Association's annual meeting, were uncovered by a study led by researchers at New York University (NYU) Langone Medical Center and the Laura and Isaac Perlmutter Cancer Center.
Stacy Loeb, MD, MSc, and colleagues utilized records from the National Prostate Cancer Register and the Prescribed Drug Register in Sweden. Of 38,570 men who developed prostate cancer between 2009 and 2012, 284 had been prescribed testosterone prior to diagnosis, compared with 1,378 men out of 192,838 who did not develop the disease, indicating a similar risk. Men treated with testosterone for more than a year were found to have experienced a 50% reduction in their risk of aggressive disease compared to nonusers.
"Based on our findings, physicians should still be watching for prostate cancer risk factors -- such as being over the age of 40, having African-American ancestry, or having a family history of the disease -- in men taking testosterone therapy, but should not hesitate to prescribe it to appropriate patients for fear of increasing prostate cancer risk," Dr Loeb stated.
"When used appropriately by men with age-related low testosterone who are otherwise healthy, testosterone replacement has been shown to improve sexual function and mood," she noted. "Overall, our study suggests that what is best for men's health is to keep testosterone levels balanced and within a normal range."
The team plans to conduct further research to investigate how maintaining normal testosterone levels may protect against aggressive prostate cancer.
New England Journal of Medicine letter questions screening trial methodology
May 6 2016. A letter published in the May 5, 2016 issue of the New England Journal of Medicine questions the findings of what has been called a landmark study on the value of prostate specific antigen (PSA) testing to screen for prostate cancer.
Jonathan E. Shoag, MD, and Sameer Mittal, MD, of New York Presbyterian Hospital, and Jim C. Hu, MD, MPH, of Weill Cornell Medical College evaluated methodology employed in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial conducted from 1993 though 2001. The trial's findings, which concluded no significant difference in prostate cancer mortality over a seven year follow-up between men who received usual care and those who were screened with annual PSA testing for six years and digital rectal examination for four years, were the basis of an updated statement by the U.S. Preventive Service Task Force in 2012 that recommended against PSA-based screening for the disease.
According to responses to a follow-up survey administered to a subgroup of patients, the portion of control participants who reported having received at least one PSA test prior to or during the trial approached 90%. "We demonstrate that the PLCO study did not compare a group of men who received PSA screening to a group of men who were not screened, but compared men who were screened to other men who were screened, and we should therefore reconsider any decisions based on the study," Dr Shoag stated.
"We expect this article to have a profound impact on the debate over the value of PSA screening," Dr Hu predicted. "While there are risks of over-diagnosis and over-treatment associated with PSA testing, it can play an important role in preventing prostate cancer deaths as part of a personalized approach to cancer screening. We're going to have to reconsider this issue."
Trial finds calorie restriction improves quality of life
May 4 2016. An article appearing on May 2, 2016 in JAMA Internal Medicine reports improvement in mood, sleep, sexual function and quality of life in nonobese men and women who practiced calorie restriction for two years.
"In humans, calorie restriction may improve health span, yet concerns remain about potential negative effects of calorie restriction," note authors Corby K. Martin, PhD, of the Pennington Biomedical Research Center and colleagues.
The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 trial assigned 66 men aged 20 to 50 years and 152 women between the ages of 20 and 47 years to diets in which calorie intake was restricted by 25% or a diet that allowed the consumption of as much food as desired. "To our knowledge, the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) trial is the first study to examine the effects of long-term calorie restriction on disease risk factors and predictors of longevity in nonobese humans," the authors observe.
Participants completed questionnaires that assessed quality of life, mood, sleep quality and sexual function before the intervention and at 12 and 24 months. Test scores at 24 months for the calorie restricted group revealed better mood, less tension, improved general health, and better sex drive and relationship quality in comparison with the non-restricted group. Calorie restricted participants also reported better sleep after one year on the diet.
"Calorie restriction among primarily overweight and obese persons has been found to improve quality of life, sleep and sexual function, and the results of the present study indicate that two years of calorie restriction is unlikely to negatively affect these factors in healthy adults; rather, calorie restriction is likely to provide some improvement," the authors conclude.
Nicotinamide riboside shows promise in regenerative medicine
May 2 2016. The June 17, 2016 issue of the journal Science reveals more positive findings for nicotinamide riboside, a natural compound that is a precursor of nicotinamide adenine dinucleotide (NAD+) found in all living cells.
A team from École Polytechnique Fédérale de Lausanne in Switzerland, along with researchers from Zurich, Canada and Brazil, found that treatment with nicotinamide riboside rejuvenated muscle stem cells in aged mice and prevented muscle stem cell senescence in a mouse model of muscular dystrophy. They also determined that the compound delayed the senescence of neural and melanocyte stem cells in addition to increasing life span in mice.
The team identified the molecular chain that regulates the function of mitochondria (the cells' energy-producing organelles) and how mitochondria change during aging. "We were able to show for the first time that their ability to function properly was important for stem cells," announced lead researcher Johan Auwerx.
"We demonstrated that fatigue in stem cells was one of the main causes of poor regeneration or even degeneration in certain tissues or organs," explained first author and PhD student Hongbo Zhang. "We gave nicotinamide riboside to two-year-old mice, which is an advanced age for them. This substance, which is close to vitamin B3, is a precursor of NAD+, a molecule that plays a key role in mitochondrial activity. And our results are extremely promising: muscular regeneration is much better in mice that received nicotinamide riboside, and they lived longer than the mice that didn't get it."
"This work could have very important implications in the field of regenerative medicine," Dr Auwerx stated. "We are not talking about introducing foreign substances into the body but rather restoring the body's ability to repair itself with a product that can be taken with food."