Saturday, March 25, 2017

Brief interval training three times a week best exercise for aging bodies


A study published this month in Cell Metabolism, however, suggests that certain sorts of workouts may undo some of what the years can do to our mitochondria.

Researchers at the Mayo Clinic in Rochester, Minn., recently conducted an experiment on the cells of 72 healthy but sedentary men and women who were 30 or younger or older than 64. After baseline measures were established for their aerobic fitness, their blood-sugar levels and the gene activity and mitochondrial health in their muscle cells, the volunteers were randomly assigned to a particular exercise regimen.

Some of them did vigorous weight training several times a week; some did brief interval training three times a week on stationary bicycles (pedaling hard for four minutes, resting for three and then repeating that sequence three more times); some rode stationary bikes at a moderate pace for 30 minutes a few times a week and lifted weights lightly on other days. A fourth group, the control, did not exercise.

After 12 weeks, the lab tests were repeated. In general, everyone experienced improvements in fitness and an ability to regulate blood sugar.

There were some unsurprising differences: The gains in muscle mass and strength were greater for those who exercised only with weights, while interval training had the strongest influence on endurance.

But more unexpected results were found in the biopsied muscle cells. Among the younger subjects who went through interval training, the activity levels had changed in 274 genes, compared with 170 genes for those who exercised more moderately and 74 for the weight lifters. Among the older cohort, almost 400 genes were working differently now, compared with 33 for the weight lifters and only 19 for the moderate exercisers.

Many of these affected genes, especially in the cells of the interval trainers, are believed to influence the ability of mitochondria to produce energy for muscle cells; the subjects who did the interval workouts showed increases in the number and health of their mitochondria — an impact that was particularly pronounced among the older cyclists.

It seems as if the decline in the cellular health of muscles associated with aging was “corrected” with exercise, especially if it was intense, says Dr. Sreekumaran Nair, a professor of medicine and an endocrinologist at the Mayo Clinic and the study’s senior author. In fact, older people’s cells responded in some ways more robustly to intense exercise than the cells of the young did — suggesting, he says, that it is never too late to benefit from exercise.

Thursday, March 23, 2017

Active surveillance preserves quality of life for prostate cancer patients

Faced with the negative quality-of-life effects from surgery and radiation treatments for prostate cancer, low risk patients may instead want to consider active surveillance with their physician, according to a study released Tuesday by the Journal of the American Medical Association (JAMA).

The Vanderbilt University Medical Center study led by Daniel Barocas, M.D., MPH, associate professor of Urologic Surgery, compared the side effects and outcomes of contemporary treatments for localized prostate cancer with active surveillance in order to guide men with prostate cancer in choosing the best treatment for them.

Surgery is considered by some to be the most definitive treatment, and there is evidence from other studies that it has better long-term cancer outcomes than radiation for higher-risk cancers, but it has more sexual and urinary side effects than radiation.

"Patients who were treated with surgery or radiation had side effects, while those who were managed with active surveillance, for the most part, did quite well," Barocas said.

"It is best to avoid treatment if you have a prostate cancer that is safe to observe. This is why most doctors recommend 'active surveillance' for low-risk cancers," he said.

Three-year survival from prostate cancer was excellent in the study at over 99 percent for patients regardless of whether they chose surgery, radiation or active surveillance. Barocas did caution that prostate cancer tends to be slow growing and patients would need to be followed for 10 years or more to find differences in mortality.

"This study shows that, despite technological advances in the treatment of prostate cancer, both surgery and radiation still have a negative effect on quality of life," said co-author David Penson, M.D., MPH, Paul V. Hamilton, M.D., and Virginia E. Howd Professor of Urologic Oncology and professor and chair of the Department of Urologic Surgery.

"Certainly, if a man has low-risk prostate cancer, he should seriously be considering active surveillance as a reasonable way to go," he said.

Erectile dysfunction and urinary incontinence were more common in men treated with surgery than radiation when studied three years after treatment, although the difference in sexual dysfunction was only apparent in patients with excellent baseline function.

"Urinary incontinence was reported as a moderate or big problem in 14 percent of men three years after surgery compared to 5 percent of men who had radiation," Barocas said.

"Men who had radiation reported more problems with bowel function and hormone side effects compared to men who had surgery, but these differences were only seen within the first year following treatment," he said.


Loss of smell linked to increased risk of early death


In a study of adults aged 40 to 90 years who were followed for 10 years, poor smell was linked with an increased risk of dying.

During the study, 411 of 1774 participants (23%) died. After controlling for demographic, health-related, and cognitive confounders, each additional correctly identified odor lowered the risk of mortality by 8%. Individuals who performed at chance level on tests (indicating complete olfactory loss) were at a 19% higher risk of death than individuals with normal smell function.

The results contribute to the growing evidence that olfactory assessments might provide insights on the aging brain.

"Our results were not explained by dementia, which was previously linked to smell loss. Instead, mortality risk was uniquely predicted by smell loss," said Dr. Jonas Olofsson, senior author of the Journal of the American Geriatrics Society study. "In our future research, we will try to pinpoint the biological processes that can explain this phenomenon."

The social costs of smell loss in older women



 A new study of older U.S. adults conducted by researchers from the Monell Center and collaborating institutions reports that a woman's social life is associated with how well her sense of smell functions. The study found that older women who do less well on a smell identification task also tend to have fewer social connections.

"Our findings confirm that the sense of smell is a key aspect of overall health in the aging population," said Johan Lundström, PhD, a cognitive neuroscientist and senior Monell author on the study. "More than 20 percent of the U.S. population over the age of 50 has a reduced sense of smell. We need to better understand how olfaction is linked to social behavior in order to improve quality of life as we age."

In the study, published online in the open access journal Scientific Reports, the researchers analyzed data from the National Social Life, Health and Aging Project (NSLHP), a population-based study of health and social factors in the United States. Collected in 2005 and 2006 from a nationally-representative sample of 3,005 American adults between the ages of 57 and 85, the NSHAP data include odor identification test scores as well as information about participants' social lives.

The researchers compared each NSHAP participant's odor identification score, an established measure of olfactory function, with an aggregated "overall social life" score, which included measures such as participants' number of friends and close relatives, and how often they socialized. The data were adjusted to control for possible confounding variables, including education level, tobacco use, and physical and mental health status.

The findings revealed a clear link between an older woman's olfactory ability and her overall social life score: women with good olfactory ability tended to have more active social lives while those with diminished olfactory function were associated with a poorer social life score.

"We know that social interactions are closely linked to health status, so older women who have a poor sense of smell may want to focus on maintaining a vital social life to help improve their overall mental and physical health," said study lead author Sanne Boesveldt, PhD, a sensory neuroscientist.

The researchers did not find the same association between olfactory function and social life in older men.

"This intriguing sex difference could suggest that smell training, which has been shown to improve a reduced sense of smell in both men and women, may have an additional beneficial function in older women by helping to restore both the sense of smell and, by extension, social well-being," said Lundström.

While the study establishes a link between the sense of smell and social life, it is not yet clear exactly how the two are connected or if the same relationship also exists in younger women. Moving forward, longitudinal studies following the same subjects over time could help clarify whether olfactory loss directly influences social life and potentially allow the researchers to identify the mechanisms involved.

Even so, knowing that olfactory status is related to social activity could already be valuable to those affected by olfactory disorders.

"You hear anecdotal accounts from women who have lost their sense of smell about having fewer friends than they had previously," said Lundström. "We hope our findings can help reassure them that they are not alone in feeling that way."

Moderate drinking linked to lower risk of some -- but not all -- heart conditions


Moderate drinking is associated with a lower risk of several, but not all, cardiovascular diseases, finds a large study of UK adults published by The BMJ today.

The finding that moderate drinking is not universally associated with a lower risk of all cardiovascular conditions suggests a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary, say the researchers.

Moderate drinking is thought to be associated with a lower risk of developing cardiovascular disease compared with abstinence or heavy drinking.

In the UK, moderate drinking is defined as no more than 14 units (112 grams) of alcohol a week.

To put this into context, one unit of alcohol is about equal to half a pint of ordinary strength beer, lager or cider (3.6% alcohol by volume) or a small pub measure (25 ml) of spirits. There are one and a half units of alcohol in small glass (125 ml) of ordinary strength wine (12% alcohol by volume). [Source: NHS Choices]

There is, however, a growing scepticism around this observation, with some experts pointing out several shortcomings in the evidence. For example, grouping non-drinkers with former drinkers, who may have stopped drinking due to poor health.

So researchers at the University of Cambridge and University College London set out to investigate the association between alcohol consumption and 12 cardiovascular diseases by analysing electronic health records for 1.93 million healthy UK adults as part of the CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records) data resource.

All participants were free from cardiovascular disease at the start of the study, and non-drinkers were separated from former and occasional drinkers to provide additional clarity in this debate.

After several influential factors were accounted for, moderate drinking was associated with a lower risk of first presenting to a doctor with several, but not all, cardiovascular conditions, including angina, heart failure and ischaemic stroke, compared with abstaining from alcohol.

However, the authors argue that it would be unwise to encourage individuals to take up drinking as a means of lowering their cardiovascular risk over safer and more effective ways, such as increasing physical activity and stopping smoking.

Heavy drinking (exceeding recommended limits) conferred an increased risk of first presenting with a range of such diseases, including heart failure, cardiac arrest and ischaemic stroke compared with moderate drinking, but carried a lower risk of heart attack and angina.

Again, the authors explain that this does not mean that heavy drinkers will not go on to experience a heart attack in the future, just that they were less likely to present with this as their first diagnosis compared with moderate drinkers.

This is an observational study, so no firm conclusions can be drawn about cause and effect. Added to which, the authors point to some study limitations that could have introduced bias.

Nevertheless, they say it is the first time this association has been investigated on such a large scale and their findings have implications for patient counselling, public health communication, and disease prediction tools.

In a linked editorial, researchers at Harvard Medical School and Johns Hopkins School of Public Health in the US say this study "does not offer a materially new view of the associations between alcohol consumed within recommended limits and risk of cardiovascular disease.

"This work, however, sets the stage for ever larger and more sophisticated studies that will attempt to harness the flood of big data into a stream of useful, reliable, and unbiased findings that can inform public health, clinical care, and the direction of future research," they conclude.


Large molecule metabolites of Resveratrol found to pass blood-ocular barrier


Inability to obtain biopsy specimens from tissues in the brain and eyes of humans had previously thwarted confirmation of resveratrol or its metabolites in nervous tissues.

Researchers at Tongji Medical College at the Huazhong University of Science & Technology in Wuhan/Hubei Province in China confirm that metabolites of resveratrol (Longevinex®) are found in ocular tissues from the outer (conjunctiva) and inner (aqueous fluid, vitreous gel) of the human eye following oral consumption. Resveratrol itself could only be detected in the conjunctiva, a clear tissue that lines the inside of the eyelids and the sclera (white of the eyes).

Tissue samples from the front and back of the inner eye were obtained directly from patients undergoing eye surgery after retinal detachment. Tissue samples were obtained from the outer eye (conjunctiva), aqueous fluid in the front of the inner eye and from the vitreous gel that fills the back of the eyes.

Blood-brain/blood-ocular barriers

While the red wine molecule resveratrol continues to astound biologists, exerting profound beneficial health effects in tissues throughout the human body, the question as to whether resveratrol or its metabolites pass through semipermeable blood/brain and blood/ocular barriers to exert biological activity had thrown a scientific cloud over application of resveratrol in humans, until now.

Researchers have demanded more evidence of the biological mechanisms of resveratrol before recommendation as a dietary supplement.

Nervous tissues in the eyes and brain are specially protected from foreign substances (germs, inflammatory agents, toxins) by tightly packed cells in the smallest blood vessels (capillaries) that block entry of large molecules. In this manner large molecules are blocked from entering nervous system.

Over 100 years ago it was discovered if that if blue dye is injected into the bloodstream, tissues throughout the human body turn blue, except the brain, spinal cord and the eyes. [Washington University] These are called the protective blood-brain and blood-ocular barriers.

The human eye has two barriers, the blood-aqueous barrier in the front of the inner eye and the blood-retinal barrier at the back of the eyes. [Survey of Ophthalmology 1979]

In prior laboratory studies resveratrol was shown to not only penetrate the blood-brain barrier but actually help maintain the integrity of this barrier. [Journal Neurophysiology Nov 2016]

Tissue delivery

In prior studies the presence of resveratrol has been shown in various major organs (liver, kidneys, lungs and heart). While resveratrol is a small molecule (molecular weight 228 Daltons), it is conjugated (attached) to larger detoxification molecules (sulfate, glucuronate) in the gut and liver. Therefore, its direct passage as a free unbound small molecule into nervous tissues has been called into question.

Resveratrol is rapidly metabolized directly in the gut (intestines) and after oral absorption in the liver.

Human Applications

An earlier study by the same researchers showed resveratrol (Longevinex®) works beneficially by its ability to expand (dilate) blood vessels at the back of the eyes thus improving circulation. [Current Eye Research Oct 2016]

In preliminary case reports, resveratrol (Longevinex®) has been shown to rescue helpless patients with advanced retinal problems and restore vision. [Nutrients Oct 2014]

Resveratrol and its metabolites have also recently been shown to protect the retina of the eyes from toxic blue light. [Archives Pharm Research Dec 2016]

A topically applied resveratrol eye drop may be closer to entering human trials after it was shown to sustain a reduction in intraocular fluid pressure that can damage the optic nerve at the back of the eyes. [Experimental Eye Research Dec 2016] Oral consumption of resveratrol has also been shown to exert similar protective properties for the optic nerve. [Neurobiology Aging May 2016]

Resveratrol has also been shown to inhibit the formation of abnormal blood vessels at the back of the eyes. [Investigative Ophthalmology April 2011]

Immediate bioavailability

While this most recent study showed only resveratrol metabolites (sulfate, glucuronate) are detected in the inner eye, the inclusion of resveratrol with quercetin is said to permit more free unbound resveratrol to initially pass through the liver before it is metabolized. [Xenobiotica 2000]

In another astonishing animal study resveratrol was metabolized in the gut (intestines) to favorably influence the balance of gut bacteria and indirectly inhibit the accumulation of atherosclerotic arterial plaque. [MBio April 2016] So at least for some tissues in the body, questions over resveratrol's absorption and bioavailability may be a moot point.

Not all eyes exhibited resveratrol or its metabolites after oral consumption, which is an obvious area for further investigation

Weight-bearing exercises promote bone formation in men



Osteoporosis affects more than 200 million people worldwide and is a serious public health concern, according to the National Osteoporosis Foundation. Now, Pamela Hinton, associate professor in the Department of Nutrition and Exercise Physiology, has published the first study in men to show that long-term, weight-bearing exercises decrease sclerostin, a protein made in the bone, and increase IGF-1, a hormone associated with bone growth. These changes promote bone formation, increasing bone density.

"People may be physically active, and many times people know they need to exercise to prevent obesity, heart disease or diabetes," Hinton said. "However, you also really need to do specific exercises to protect your bone health."

In the study, men 25- to 60-years-old who had low-bone mass were split into two groups. One group performed resistance training exercises such as lunges and squats using free weights. The other group performed various types of jumps, such as single-leg and double-leg jumps. After 12 months of performing the exercises, Hinton then compared the levels of bone proteins and hormones in the blood.

"We saw a decrease in the level of sclerostin in both of these exercise interventions in men," Hinton said. "When sclerostin is expressed at high levels, it has a negative impact on bone formation. In both resistance and jump training, the level of sclerostin in the bone goes down, which triggers bone formation."

The other significant change Hinton observed was an increase in the hormone IGF-1. Unlike sclerostin, IGF-1 triggers bone growth. The decrease of harmful sclerostin levels and the increase in beneficial IGF-1 levels confirmed Hinton's prior research that found both resistance training and jump training have beneficial effects on bone growth.

To increase bone mass and prevent osteoporosis, Hinton recommends exercising specifically to target bone health. While exercises such as swimming and cycling are beneficial to overall health, these activities do not strengthen the skeleton. Hinton suggests also doing exercise targeted for bone health, such as resistance training and jump training.

The study, "Serum sclerostin decreases following 12 months of resistance- or jump-training in men with low bone mass," was published in Bone.