As we age, we typically experience declines in the quality of our sleep. Mindfulness meditation is a self-administered approach that intentionally focuses one’s attention on the emotions, thoughts and sensations occurring in the present moment. David Black, from University of Southern California (California, USA), and colleagues enrolled 49 men and women, ages 55 years and older, whoe experienced moderately (or greater) disturbed sleep, who were divided into two groups. One group visited the study center for six weekly two-hour sessions of a course in Mindfulness Awareness Practices for daily living. Those included meditation, eating, walking, movement and friendly or loving-kindness practices. A certified teacher led the exercises and also instructed participants to meditate for five minutes daily, gradually increasing to 20 minutes daily. The other group attended six weeks of a sleep hygiene and education course, where they learned about sleep problems, and self-care methods for improving sleep, and weekly behavioral sleep hygiene strategies. Prior to the start of the six-week programs, the average sleep quality questionnaire score was 10. At the end of the study period, those in the meditation group demonstrated improvement in their sleep score by an average of 2.8 points, compared to 1.1 points in the sleep hygiene group. Among those in the meditation group, daytime impairments, including symptoms of insomnia, fatigue and depression, were improved as well. The study authors conclude that: “Formalized mindfulness-based interventions have clinical importance by possibly serving to remediate sleep problems among older adults in the short term, and this effect appears to carry over into reducing sleep-related daytime impairment that has implications for quality of life.”

Reference:

David S. Black, PhD, MPH1; Gillian A. O?Reilly, BS1; Richard Olmstead, PhD2; Elizabeth C. Breen, PhD2; Michael R. Irwin, MD2. Mindfulness Meditation and Improvement in Sleep Quality and Daytime Impairment Among Older Adults With Sleep Disturbances

Out of a ‘haystack’ of 40,000 genes from three different organisms, scientists at ETH Zurich and a research consortium in Jena have found genes that are involved in physical ageing. If you influence only one of these genes, the healthy lifespan of laboratory animals is extended and possibly that of humans, too.

With advancements in molecular genetic methods in recent decades, the search for the genes involved in the aging process has greatly accelerated. Until now, this was mostly limited to genes of individual model organisms such as the C. elegans nematode, which revealed that around one percent of its genes could influence life expectancy. However, researchers have long assumed that such genes arose in the course of evolution and in all living beings whose cells have a preserved a nucleus from yeast to humans.

Combing through 40,000 genes

Researchers at ETH Zurich and the JenAge consortium from Jena have now systematically gone through the genomes of three different organisms in search of the genes associated with the aging process that are present in all three species and thus derived from the genes of a common ancestor. Although they are found in different organisms, these so-called orthologous genes are closely related to each other, and they are all found in humans, too.

In order to detect these genes, the researchers examined around 40,000 genes in the nematode C. elegans, zebra fish and mice. By screening them, the scientists wanted to determine which genes are regulated in an identical manner in all three organisms in each comparable aging stage young, mature and old; i.e. either are they upregulated or downregulated during aging.

As a measure of gene activity, the researchers measured the amount of messenger RNA (mRNA) molecules found in the cells of these animals. mRNA is the transcript of a gene and the blueprint of a protein. When there are many copies of an mRNA of a specific gene, it is very active; the gene is upregulated. Fewer mRNA copies, to the contrary, are regarded as a sign of low activity, explains Professor Michael Ristow, coordinating author of the recently published study and Professor of Energy Metabolism at ETH Zurich.

Out of this volume of information, the researchers used statistical models to establish an intersection of genes that were regulated in the same manner in the worms, fish and mice. This showed that the three organisms have only 30 genes in common that significantly influence the aging process.

Reduce gene activity, live longer

By conducting experiments in which the mRNA of the corresponding genes were selectively blocked, the researchers pinpointed their effect on the aging process in nematodes. With a dozen of these genes, blocking them extended the lifespan by at least five percent.

One of these genes proved to be particularly influential: the bcat-1 gene. “When we blocked the effect of this gene, it significantly extended the mean lifespan of the nematode by up to 25 percent,” says Ristow.

The researchers were also able to explain how this gene works: the bcat-1 gene carries the code for the enzyme of the same name, which degrades so-called branched-chain amino acids. Naturally occurring in food protein building blocks, these include the amino acids L-leucine, L-isoleucine and L-valine.

When the researchers inhibited the gene activity of bcat-1, the branched-chain amino acids accumulated in the tissue, triggering a molecular signalling cascade that increased longevity in the nematodes. Moreover, the timespan during which the worms remained healthy was extended. As a measure of vitality, the researchers measured the accumulation of aging pigments, the speed at which the creatures moved, and how often the nematodes successfully reproduced. All of these parameters improved when the scientists inhibited the activity of the bcat-1 gene.

The scientists also achieved a life-extending effect when they mixed the three branched-chain amino acids into the nematodes’ food. However, the effect was generally less pronounced because the bcat-1 gene was still active, which meant that the amino acids continued to be degraded and their life-extending effects could not develop as effectively.

Conserved mechanism

Ristow has no doubt that the same mechanism occurs in humans. “We looked only for the genes that are conserved in evolution and therefore exist in all organisms, including humans,” he says.

In the present study, he and his Jena colleagues from the Leibniz Institute on Aging, the Leibniz Institute for Natural Product Research and Infection Biology, the Jena University Hospital and the Friedrich Schiller University purposefully opted not to study the impact on humans. But a follow-up study is already being planned. “However we cannot measure the life expectancy of humans for obvious reasons,” says the ETH professor. Instead, the researchers plan to incorporate various health parameters such as cholesterol or blood sugar levels in their study to obtain indicators on the health status of their subjects.

Health costs could be massively reduced

Ristow says that the multiple branched-chain amino acids are already being used to treat liver damage and are also added to sport nutrition products. “However, the point is not for people to grow even older, but rather to stay healthy for longer,” says the internist. The study will deliver important indicators on how the aging process could be influenced and how age-related diseases such as diabetes or high blood pressure could be prevented. In light of unfavourable demographics and steadily increasing life expectancy, it is important to extend the healthy life phase and not to reach an even higher age that is characterised by chronic diseases, argue the researchers. With such preventive measures, an elderly person could greatly improve their quality of life while at the same time cutting their healthcare costs by more than half.

As medicine has improved, we are increasing our ability to treat disease and improve longevity. The deterioration of the body with age, though, is a whole other matter.

Scientists suggest that all we might need is some “house-keeping” of the brain, according to research just published in an early edition of the journal PNAS by a Portuguese team from the Centre for Neuroscience and Cell Biology (CNC) of the University of Coimbra.

The researchers might have also solved a 70-year old mystery: How can calorie restriction (a diet with low calories without malnutrition) delay ageing and increase longevity in animals from dogs to mice?

In their new study, Claudia Cavadas and her group have discovered that the key to this diet appears to be its ability to increase autophagy – the mechanism that recycles unwanted molecules in the cells, thereby avoiding malfunction in the hypothalamus, which has just been identified as the “control centre” for ageing. They also have identified the molecule that controls the process. It’s called neuropeptide Y (NPY), and its discovery raises the possibility that NPY could be used to develop techniques to control aging instead of just treating its consequences, like we do now.

The discovery may be a key to stopping the development of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s, a huge step forward, considering that science has thus far been incapable of treating, stopping or even fully understanding them. And in a rapidly aging world, a better control of these kinds of problems can prove crucial for everyone’s survival.

In fact, according to the UN, in less than a decade, 1 billion people will be older than 60. In Japan, more than 30% of the population is older than 60 years old, and in Europe, 16% of the population is over 65. So it is clear that our increasingly aging population needs to be kept as healthy and active as possible, or it will be financially and socially impossible for the world to cope. It is no surprise, then, that research to understand and control the deteriorating effects of aging is now a priority.

One thing that has been clear for a while now is that autophagy (or better, a reduction of it) is at the centre of the aging process. Low levels of autophagy?that is, impaired cellular “house-keeping”? is linked to ageing and age-related neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and Huntington’s diseases. This is easily explained as autophagy clears the cellular “debris” keeping neurons in good working order. The importance of the process in the brain is no surprise, since neurons have a lower ability to replenish themselves once they die or malfunction.

But about a year ago, there was a remarkable discovery that changed the field: The hypothalamus, which is a brain area that regulates energy and metabolism, was identified as the control centre for whole-body aging.

To Cavadas and her group, who have worked on aging and neuroscience for a long time, this was particularly exciting. They knew calorie restriction delayed aging and increased longevity and increased autophagy in the hypothalamus; but they also knew that it did the same to NPY and that mice without NPY did not respond to calorie restriction. Furthermore NPY, like autophagy, diminishes with age. All this, together with the discovery of the new role of the hypothalamus, suggested that this brain area and NPY were the key to the rejuvenating effects of calorie restriction.

So now all that was left was to connect the dots, and for that, the researchers started by taking neurons from the hypothalami of mice and growing them in a medium that mimicked a low caloric diet. They then measured rates of autophagy. As expected, autophagy levels in this calorie-restriction-like medium were much higher than normal, unless NPY was blocked, in which case the medium had no consequences on the neurons. So calorie restriction effect on the hypothalamic autophagy appeared to depend on NPY. To confirm this, the researchers then tested mice genetically modified to produce higher than normal quantities of NYP in their hypothalami. As expected, this led to higher levels of autophagy.

So calorie restriction seems to work by increasing the levels of NPY in the hypothalamus, which in turn triggers an increase in autophagy in its neurons, “rejuvenating” them and delaying aging symptoms. Cavadas and colleagues also identified the biochemical pathways involved in the NPY effect. This, however, is not the whole story, as it still does not explain why in some species, such as wild mice, calorie restriction has no effect.

But by adding a new piece to the puzzle of aging, the group’s research is an important step toward delaying the the body’s deterioration, allowing individuals to have healthier lives until the end, particularly with regard to the brain. Age-related neurodegenerative diseases seem to be unstoppable at the moment, and are not only an economic but also a huge social burden as patients became totally dependent on their families or the state.

In fact, in the US, more than 5 million people already suffer from Alzheimer’s (1 million have Parkinson’s), while in the UK this number is reaching 1 million. Just in the care of dementia patients, the UK health system is spending more than ?26 billion yearly (the equivalent to 38 billion dollars or 36 billion Euros). Age-related neurodegenerative diseases are already the fourth highest disease burden in the western world, and growing.

It will be interesting to further understand the long-debated mystery of the mechanism behind calorie restriction, and test to see if it works on humans as some believe (it does not work, for example, on wild mice). In fact, during World War II in Europe, when food was short, there was a sharp decrease in heart diseases (which are age-related) that rapidly rose once the war ended. The same reduction is observed in Okinawa island in Japan, where people eat on average less 30% of calories than the rest of the country. Whether a coincidence or not, it should be interesting to know what that that means in our “junk-food” society.

Using sugar, silicone, and a 3D printer, bioengineers at Rice University and surgeons at the University of Pennsylvania have created an implant with an intricate network of blood vessels that points toward a future of growing replacement tissues and organs for transplantation.

The research may provide a method to overcome one of the biggest challenges in regenerative medicine, i.e., how to deliver oxygen and nutrients to all cells in an artificial organ or tissue implant that takes days or weeks to grow in the lab prior to surgery.

The new study was performed by a research team led by Jordan Miller, Ph.D., assistant professor of bioengineering at Rice, and Pavan Atluri, M.D., assistant professor of surgery at Penn. The study showed that blood flowed normally through test constructs that were surgically connected to native blood vessels. The study (?In vivo anastomosis and perfusion of a 3D printed construct containing microchannel networks?) was published in Tissue Engineering Part C: Methods.

Dr. Miller said one of the hurdles of engineering large artificial tissues, such as livers or kidneys, is keeping the cells inside them alive. Tissue engineers have typically relied on the body’s own ability to grow blood vessels, for example, by implanting engineered tissue scaffolds inside the body and waiting for blood vessels from nearby tissues to spread to the engineered constructs. Dr. Miller noted that that process can take weeks, and cells deep inside the constructs often starve or die from lack of oxygen before they’re reached by the slow-approaching blood vessels.

“We had a theory that maybe we shouldn’t be waiting,” he explained. “We wondered if there were a way to implant a 3D printed construct where we could connect host arteries directly to the construct and get perfusion immediately. In this study, we are taking the first step toward applying an analogy from transplant surgery to 3D printed constructs we make in the lab.”

Dr. Miller and his team thought long-term about what the needs would be for transplantation of large tissues made in the laboratory. “What a surgeon needs in order to do transplant surgery isn’t just a mass of cells; the surgeon needs a vessel inlet and an outlet that can be directly connected to arteries and veins,” he added.

The research team worked together to develop a proof-of-concept construct, a small silicone gel about the size of a small candy gummy bear, using 3D printing. But rather than printing a whole construct directly, the scientists fabricated sacrificial templates for the vessels that would be inside the construct.

It’s a technique pioneered by Dr. Miller in 2012 and inspired by the intricate sugar glass cages crafted by pastry chefs to garnish desserts.

Using an open-source 3D printer that lays down individual filaments of sugar glass one layer at a time, the researchers printed a lattice of would-be blood vessels. Once the sugar hardened, the investigators placed it in a mold and poured in silicone gel. After the gel cured, Dr. Miller’s team dissolved the sugar, leaving behind a network of small channels in the silicone.

“They don’t yet look like the blood vessels found in organs, but they have some of the key features relevant for a transplant surgeon,” said Dr. Miller. “We created a construct that has one inlet and one outlet, which are about 1 millimeter in diameter, and these main vessels branch into multiple smaller vessels, which are about 600 to 800 microns.”

Collaborating surgeons at Penn in Dr. Atluri’s group connected the inlet and outlet of the engineered gel to a major artery in a small animal model. Using Doppler imaging technology, the team observed and measured blood flow through the construct and found that it withstood physiologic pressures and remained open and unobstructed for up to three hours.

“This study provides a first step toward developing a transplant model for tissue engineering where the surgeon can directly connect arteries to an engineered tissue,” said Dr. Miller. “In the future we aim to utilize a biodegradable material that also contains live cells next to these perfusable vessels for direct transplantation and monitoring long term.”

Back in the 1950s in a weird, vampiric experiment, scientists first showed that connecting the circulatory systems of old and young mice seems to rejuvenate the more elderly animals. A handful of labs have recently been racing to find factors in young blood that may explain this effect. Now, a Harvard University group that claims to have found one such antiaging protein has published a study countering critics who dismissed the work on the molecule as flawed.

Harvard stem cell biologist Amy Wagers, cardiologist Richard Lee of the Harvard-affiliated Brigham and Women?s Hospital in Boston, and their colleagues claim that a specific protein, GDF11, may explain young blood?s beneficial effects. They have reported that blood levels of GDF11 drop in mice as the animals get older and that injecting old mice with GDF11 can partially reverse age-related thickening of the heart. In two papers last year in Science, Wagers and collaborators also reported that GDF11 can rejuvenate the rodents? muscles and brains.

Last May, however, a group led by muscle disease researcher David Glass of the Novartis Institutes for Biomedical Research in Cambridge, Massachusetts, reported that the antibody the Harvard team used to measure levels of GDF11 also detected myostatin (also known as GDF8), a similar protein that hinders muscle growth. The Novartis group concluded from a different assay that GDF11 levels in blood actually rise with age in rats and people. And in their lab, GDF11 injections inhibited muscle regeneration in young mice.

Now, the Wagers and Lee group says the assay Novartis used to detect GDF11 and GDF8 was itself flawed. They found that the main protein detected by the antibody test is immunoglobulin, another protein that rises in blood level with age. Mice lacking the gene for immunoglobulin tested negative for the active form of GDF11/8 that the Novartis assay was thought to reveal, they report today online in Circulation Research.

?They actually had very consistent findings to ours with respect to the blood levels of GDF11/8 with the antibody we all used,? Wagers says. But ?their interpretation was confused by this case of mistaken identity.? A recently published study by University of California, San Francisco, researchers finding that GDF11/8 blood levels decline with age in people and are low in those with heart disease supports the contention that GDF11 has an antiaging role, her paper notes.

The Harvard team?s paper also disputes a recent study in which cardiac physiologist Steven Houser?s group at Temple University in Philadelphia, Pennsylvania, found that GDF11 injections have no effect on heart thickness in older mice. The problem, according to Wagers, is that commercially purchased GDF11 can vary in the actual level and activity of protein. ?It wasn?t something that affected us early on, but we figured out it was an issue,? she says. That lot-to-lot variability likely explains why the Houser group didn?t see any effects from GDF11 at the same apparent dose the Harvard group reported using, she adds. (Lee says his group now suspects that the dose was higher than they realized.)

To back up their earlier results, Wagers and collaborators again show in the new paper that daily GDF11 injections can shrink heart muscle in both old and new mice. But this time they note another observation: The mice also lost weight. ?We don?t have much insight into that right now, but we?re looking into it,? Wagers says. She says the findings suggest that as with other hormones, GDF11 may have ?a therapeutic window? for beneficial effects?too much may cause harm.

Houser says he agrees that one of the Novartis team?s assays for GDF11 was probably detecting immunoglobulin. But Houser notes that the group also used a different assay to detect GDF11 and that isn?t challenged by the new paper. (David Glass makes the same point.) Sorting out what role GDF11 may play in aging is important, Houser adds. ?I’m going to be 65 in a couple months. I’d love to have something that improves my heart, brain, and muscle function,? Houser says. ?I think the field is going to figure this out and this is another piece of the puzzle.?