lroot on March 1st, 2017

Autophagy

A molecular key to aging of the blood and immune system has been discovered in new research conducted at UC San Francisco, raising hope that it may be possible to find a way to slow or reverse many of the effects of aging.

The key is a link between the health of a rare population of adult stem cells that arise early in development and are responsible for replenishing all blood cell types throughout a lifetime, and a newly identified role for autophagy, an important cellular cleanup and recycling process that was the focus of the 2016 Nobel Prize in Physiology or Medicine.

In their new study, published online March 1 in Nature, the UCSF team discovered that in addition to its normal role in cellular waste-processing, autophagy also is needed for the orderly maintenance of blood-forming hematopoietic stem cells (HSCs), the adult stem cells that give rise to red blood cells, which carry oxygen, and to platelets, as well as the entire immune system.

The researchers found that autophagy keeps HSCs in check by allowing metabolically active HSCs to return to a resting, quiescent state akin to hibernation. This is the default state of adult HSCs, allowing their maintenance for a lifetime.

According to Emmanuelle Passegué, PhD, the senior scientist for the study, “This is a previously unknown role for autophagy in stem cell biology.”

Failure to activate autophagy has profound impacts on the blood system, Passegué’s team found, leading to the unbalanced production of certain types of blood cells. Defective autophagy also diminished the ability of HSCs to regenerate the entire blood system when they were transplanted into irradiated mice, a procedure similar to bone marrow transplantation.

The researchers determined that 70 percent of HSCs from old mice were not undergoing autophagy, and these cells exhibited the dysfunctional features common among old HSCs. However, the 30 percent of old HSCs that did undergo autophagy looked and acted like HSCs from younger mice.

Passegué led the study while she was a professor of medicine with the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCSF. In January she became an Alumni Professor in the Department of Genetics & Development and the director of the Columbia Stem Cell Initiative at Columbia University Medical Center.

Scientists have identified many different tissue-specific stem cells, all of whose performance declines with age, Passegué said. Finding out how this occurs has been an active area of research, and a focus of her laboratory group in recent years.

In a large series of experiments and analyses, many conducted by the study’s first author, Theodore Ho, a UCSF graduate student, the scientists compared characteristics of HSCs from old mice with those of HSCs from younger mice that had been genetically programmed so that they could not undergo autophagy. They found that loss of autophagy in young mice was sufficient to drive many of the defects that arise naturally in the blood of old mice, including changes in the cellular appearance of HSCs and a disruption in the normal proportions of the various types of blood cells, characteristics of old age.

Previous research had shown that autophagy causes the formation of “sacs” within cells that can engulf and enzymatically digest molecules and even major cellular structures, including mitochondria, the cell’s biochemical power plants. But in the new study, the researchers found that genetically programmed loss of autophagy resulted in the accumulation of activated mitochondria with increased oxidative metabolism that triggered chemical modifications of DNA in HSCs.

These “epigenetic” DNA modifications altered the activities of genes in a way that changed the developmental fate of HSCs. They triggered disproportionate production of certain blood cells and reduced the ability of HSCs to regenerate the entire blood system when transplanted. This result was similar to what the researchers observed in the majority of old HSCs that failed to activate autophagy.

In contrast, the minority of old HSCs that still exhibited significant levels of autophagy were able to keep their mitochondria and metabolism in check, and could re-establish a healthy blood system following transplantation, similar to HSCs from young mice.

However, in a hopeful sign for potential future therapies to rejuvenate blood stem cells, the researchers succeeded in restoring autophagy to old HSCs by treating them with pharmacological agents in a lab dish.

“This discovery might provide an interesting therapeutic angle to use in re-activating autophagy in all of the old HSCs, to slow the aging of the blood system and to improve engraftment during bone marrow or HSC transplantation,” Passegué said. “It is our hope that the end point will be a way to really improve the fitness of stem cells and to use that capability to help the immune systems.”

Reference: Theodore T. Ho, Matthew R. Warr, Emmalee R. Adelman, Olivia M. Lansinger, Johanna Flach, Evgenia V. Verovskaya, Maria E. Figueroa & Emmanuelle Passegué; Autophagy maintains the metabolism and function of young and old stem cells, Nature (2017). DOI: 10.1038/nature21388

lroot on February 22nd, 2017

Stem Cells

Our blood stem cells generate around a thousand billion new blood cells every day. But the blood stem cells’ capacity to produce blood declines as we age. This leads to lowered immunity and other age related problems. Now for the first time, a research team at Lund University in Sweden has succeeded in rejuvenating blood stem cells that had become less functional in aging mice. The study is published in Nature Communications.

When we are young, our blood stem cells produce an even and well-balanced number of red and white blood cells according to need. As we age, however, the capacity of the blood stem cells to produce the number of blood cells we need declines.

“This type of age-related change can have major consequences as it can lead to an imbalance in stem cell production. For example, a reduced production of immune cells or excessive production of other types of cells” explains David Bryder, who headed the study at Lund University.

A fundamental question was whether blood stem cells age differently within a single individual or whether all blood stem cells are equally affected by advancing age. In an initial stage, it was therefore important to genetically mark old blood stem cells, to enable the identification and tracking of those most affected by age. In the next step, these traceable cells were reprogrammed to another type of stem cell known as iPS cells, which can generate all cells in an individual and not only blood cells. When the cells are reprogrammed, their identity is ?re-set”; when these reprogrammed iPS cells formed new blood stem cells, the researchers observed that the re-set had entailed a rejuvenation of the cells.

“We found that there was no difference in blood-generating capacity when we compared the reprogrammed blood stem cells with healthy blood stem cells from a young mouse. This is, as far as we know, the first time someone has directly succeeded in proving that it is possible to recreate the function of young stem cells from a functionally old cell?, says Martin Wahlestedt, the first author of the study.

The research team’s studies have also thereby shown that many age-related changes in the blood system cannot be explained by mutations in the cells’ DNA. If the changes depended on permanent damage at the DNA level, the damage would still be present after the re-set. Instead, epigenetic changes appear to underlie the decline in function associated with advancing age.

“Our findings justify further research to improve the function of human blood stem cells” concludes David Bryder.

Reference: Martin Wahlestedt, Eva Erlandsson, Trine Kristiansen, Rong Lu, Cord Brakebusch, Irving L. Weissman, Joan Yuan, Javier Martin-Gonzalez, David Bryder. Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate. Nature Communications, 2017; 8: 14533 DOI: 10.1038/ncomms14533

lroot on February 18th, 2017

Adult Stem Cells

Adult stem cells collected directly from human fat have been used in stem cell treatments in many countries during the past 10 years. They are more stable than other cells such as fibroblasts from the skin and have the potential for use in anti-aging treatments, according to researchers from the Perelman School of Medicine at the University of Pennsylvania. They made the discovery after developing a new model to study chronological aging of these cells. They published their findings this month in the journal Stem Cells.

Chronological aging shows the natural life cycle of the cells as opposed to cells that have been unnaturally replicated multiple times or otherwise manipulated in a lab. In order to preserve the cells in their natural state, Penn researchers developed a system to collect and store them without manipulating them, making them available for this study. They found stem cells collected directly from human fat called adipose-derived stem cells (ASCs) can make more proteins than originally thought. This gives them the ability to replicate and maintain their stability, a finding that held true in cells collected from patients of all ages.

“Our study shows these cells are very robust, even when they are collected from older patients,” said Ivona Percec, MD, director of Basic Science Research in the Center for Human Appearance and the study’s lead author. “It also shows these cells can be potentially used safely in the future, because they require minimal manipulation and maintenance.”

Stem cells are currently used in a variety of anti-aging treatments and are commonly collected from a variety of tissues. But Percec’s team specifically found ASCs to be more stable than other cells, a finding that can potentially open the door to new therapies for the prevention and treatment of aging-related diseases.

“Unlike other adult human stem cells, the rate at which these ASCs multiply stays consistent with age,” Percec said. “That means these cells could be far more stable and helpful as we continue to study natural aging.”

ASCs are not currently approved for direct use by the Food and Drug Administration in the United States. Percec said the next step for her team is to study how chromatin is regulated in ASCs. Essentially, they want to know how tightly the DNA is wound around proteins inside these cells and how this affects aging. The more open the chromatin is, the more the traits affected by the genes inside will be expressed. Percec said she hopes to find out how ASCs can maintain an open profile with aging.

lroot on February 2nd, 2017

Jack LaLanne

You can rebuild them, even if you are middle-aged or older.

“Our lab and others have shown repeatedly” that older muscles will grow and strengthen, says Marcas Bamman, a professor of integrative biology at the University of Alabama at Birmingham. In his studies, men and women in their 60s and 70s who began supervised weight training developed muscles that were as large and strong as those of your average 40-year-old. Jack LaLanne continued to work out and maintain large and strong muscles until he passed away at the age of 96 years old.

The process of bulking up works differently in older people than in the young. Skeletal muscles are composed of various types of fibers and “two things happen” to those fibers after we reach middle age, Dr. Bamman says. Some muscle fibers die, especially if we have not been exercising our muscles much. Sedentary adults can lose 30 to 40 percent of the total number of fibers in their muscles by the time they are 55, Dr. Bamman says.

Others of the fibers remain alive but shrink and atrophy as we age.

Young people who work out add new muscle fibers and also plump up their existing ones. Older people do not. We increase the size of our atrophied muscle fibers with exercise but, for a variety of physiological reasons, do not add to the number of fibers, Dr. Bamman says.

But in practical terms, who cares? Older muscles will become larger and stronger if you work them, Dr. Bamman says.

The key, he continues, is regular and progressive weight training. If you don’t belong to a gym, consider joining one, and then plan on tiring yourself. In order to initiate the biochemical processes that lead to larger, stronger fibers, Dr. Bamman says, you should push your muscles until they are exhausted.

In his studies, volunteers used weights calibrated so that the lifters could barely complete a set of eight to 12 repetitions before their arms or legs grew leaden and they had to rest. They repeated each set two or three times and visited the gym three times per week. If you are new to weight workouts, ask for an orientation at your gym or consult an athletic trainer who often works with older clients.

Reference: Bickel CS1, Cross JM, Bamman MM. Exercise dosing to retain resistance training adaptations in young and older adults. Med Sci Sports Exerc. 2011 Jul;43(7):1177-87.

lroot on February 1st, 2017

BPA Free

Companies advertise “BPA-free” as a safer version of plastic products ranging from water bottles to sippy cups to toys. Many manufacturers stopped using Bisphenol A to strengthen plastic after animal studies linked it to early puberty and a rise in breast and prostate cancers.

Yet new UCLA research demonstrates that BPS (Bisphenol S), a common replacement for BPA, speeds up embryonic development and disrupts the reproductive system.

Reported in the Feb. 1 edition of the journal Endocrinology, the animal study is the first to examine the effects of BPA and BPS on key brain cells and genes that control the growth and function of organs involved in reproduction.

“Our study shows that making plastic products with BPA alternatives does not necessarily leave them safer,” explained senior author Nancy Wayne, a reproductive endocrinologist and a professor of physiology at the David Geffen School of Medicine at UCLA.

Using a zebrafish model, Wayne and her colleagues found that exposure to low levels of BPA and BPS—equivalent to the traces found in polluted river waters—altered the animals’ physiology at the embryonic stage in as quickly as 25 hours.

“Egg hatching time accelerated, leading to the fish equivalent of premature birth,” said Wayne, who is also UCLA’s associate vice chancellor for research. “The embryos developed much faster than normal in the presence of BPA or BPS.”

The UCLA team, which included first author Wenhui Qiu, a visiting graduate student from Shanghai University, chose to conduct the study in zebrafish because their transparent embryos make it possible to “watch” cell growth as it occurs.

Using fluorescent-green protein tags, the researchers tracked the fishes’ development of reproductive endocrine brain cells, which control puberty and fertility. In a second finding, the team discovered that the number of endocrine neurons increased up to 40 percent, suggesting that BPA overstimulates the reproductive system.

“Exposure to low levels of BPA had a significant impact on the embryos’ development of brain cells that control reproduction, and the genes that control reproduction later in life,” said Wayne. “We saw many of these same effects with BPS found in BPA-free products. BPS is not harmless.”

Wayne suspects that overstimulation of the neurons that regulate reproduction could lead to premature puberty and disruption of the reproductive system. Her lab plans to investigate this question in a future study.

After uncovering her first finding about BPA in 2008, Wayne immediately discarded all of the plastic food containers in her home and replaced them with glass. She and her family purchase food and drinks packaged in glass whenever possible.

“Our findings are frightening and important,” emphasized Wayne. “Consider it the aquatic version of the canary in the coal mine.”

Finally, the researchers were surprised to find that both BPA and BPS acted partly through an estrogen system and partly through a thyroid hormone system to exert their effects.

“Most people think of BPA as mimicking the effects of estrogen. But our work shows that it also mimics the actions of thyroid hormone,” said Wayne. “Because of thyroid hormone’s important influence on brain development during gestation, our work holds important implications for general embryonic and fetal development, including in humans.”

Researchers have proposed that endocrine-disrupting chemicals may be contributing to the U.S.’ rise in premature human births and early onset of puberty over the past couple of decades.

“Our data support that hypothesis,” said Wayne. “If BPA is impacting a wide variety of animal species, then it’s likely to be affecting human health. Our study is the latest to help show this with BPA and now with BPS.”

BPA can leach into food, particularly under heat, from the lining of cans and from consumer products such as water bottles, baby bottles, food-storage containers and plastic tableware. BPA can also be found in contact lenses, eyeglass lenses, compact discs, water-supply pipes, some cash register and ATM receipts, as well as in some dental sealants and composites. The U.S. and Europe were expected to manufacture more than 5 million tons of products containing the additives in 2015.

Telomeres

A recent study showed that “cells age faster with a sedentary lifestyle. Chronological age doesn’t always match biological age,” according to Aladdin Shadyab, PhD, lead author of the study with the Department of Family Medicine and Public Health at UC San Diego School of Medicine.

Telomeres are tiny caps found on the ends of DNA strands, like the plastic tips of shoelaces, that protect chromosomes from deterioration. As a cell ages, its telomeres naturally shorten and fray, but health and lifestyle factors, such as obesity and smoking, may accelerate that process.

The study, publishing online January 18 in the American Journal of Epidemiology, found elderly women with less than 40 minutes of moderate-to-vigorous physical activity per day and who remain sedentary for more than 10 hours per day have shorter telomeres.

The researchers also found that elderly women who sit for more than 10 hours a day with low physical activity have cells that are biologically older by eight years compared to women who are less sedentary.

Shadyab and his research team believe they are the first to objectively measure how the combination of sedentary time and exercise can impact the aging biomarker.

Nearly 1,500 women, ages 64 to 95, participated in the study. The women are part of the larger Women’s Health Initiative (WHI), a national, longitudinal study investigating the determinants of chronic diseases in postmenopausal women. The participants completed questionnaires and wore an accelerometer on their right hip for seven consecutive days during waking and sleeping hours to track their movements.

“We found that women who sat longer did not have shorter telomere length if they exercised for at least 30 minutes a day, the national recommended guideline,” said Shadyab. “Discussions about the benefits of exercise should start when we are young, and physical activity should continue to be part of our daily lives as we get older, even at 80 years old.”

Shadyab said future studies will examine how exercise relates to telomere length in younger populations and in men.

Reference: Aladdin H. Shadyab et al. Associations of Accelerometer-Measured and Self-Reported Sedentary Time With Leukocyte Telomere Length in Older Women. American Journal of Epidemiology, January 2017 DOI: 10.1093/aje/kww196

Abstract: Few studies have assessed the association of sedentary time with leukocyte telomere length (LTL). In a cross-sectional study conducted in 2012–2013, we examined associations of accelerometer-measured and self-reported sedentary time with LTL in a sample of 1,481 older white and African-American women from the Women’s Health Initiative and determined whether associations varied by level of moderate- to vigorous-intensity physical activity (MVPA). The association between sedentary time and LTL was evaluated using multiple linear regression models. Women were aged 79.2 (standard deviation, 6.7) years, on average. Self-reported sedentary time was not associated with LTL. In a model adjusting for demographic characteristics, lifestyle behaviors, and health-related factors, among women at or below the median level of accelerometer-measured MVPA, those in the highest quartile of accelerometer-measured sedentary time had significantly shorter LTL than those in the lowest quartile, with an average difference of 170 base pairs (95% confidence interval: 4, 340). Accelerometer-measured sedentary time was not associated with LTL in women above the median level of MVPA. Findings suggest that, on the basis of accelerometer measurements, higher sedentary time may be associated with shorter LTL among less physically active women.

lroot on January 12th, 2017

Red Chili Peppers

Like spicy food? If so, you might live longer, say researchers at the Larner College of Medicine at the University of Vermont, who found that consumption of hot red chili peppers is associated with a 13 percent reduction in total mortality in a large prospective study.

For centuries, peppers and spices have been thought to improve health and longevity, but only one other scientific study conducted in China and published in 2015 has previously examined chili pepper consumption and its association with mortality. This new study corroborates the earlier study’s findings.

Using National Health and Nutritional Examination Survey (NHANES) III data collected from more than 16,000 Americans who were followed for up to 23 years, medical student Mustafa Chopan ’17 and Professor of Medicine Benjamin Littenberg, M.D., examined the baseline characteristics of the participants according to hot red chili pepper consumption. They found that consumers of hot red chili peppers tended to be “younger, male, white, Mexican-American, married, and to smoke cigarettes, drink alcohol, and consume more vegetables and meats,” in comparison to participants who did not consume red chili peppers. They examined data from a median follow-up of 18.9 years and observed the number of deaths and then analyzed specific causes of death.

“Although the mechanism by which peppers could delay mortality is far from certain, Transient Receptor Potential (TRP) channels, which are primary receptors for pungent agents such as capsaicin (the principal component in chili peppers), may in part be responsible for the observed relationship,” say the study authors.

There are some possible explanations for red chili peppers’ health benefits, state Chopan and Littenberg in the study. Among them are the fact that capsaicin is believed to play a role in cellular and molecular mechanisms that prevent obesity and modulate coronary blood flow, and also possesses antimicrobial properties that “may indirectly affect the host by altering the gut microbiota.”

“Because our study adds to the generalizability of previous findings, chili pepper or even spicy food consumption may become a dietary recommendation and/or fuel further research in the form of clinical trials,” says Chopan.

Reference: Mustafa Chopan, Benjamin Littenberg. The Association of Hot Red Chili Pepper Consumption and Mortality: A Large Population-Based Cohort Study. PLOS ONE, 2017; 12 (1): e0169876 DOI: 10.1371/journal.pone.0169876

Abstract: “The evidence base for the health effects of spice consumption is insufficient, with only one large population-based study and no reports from Europe or North America. Our objective was to analyze the association between consumption of hot red chili peppers and mortality, using a population-based prospective cohort from the National Health and Nutritional Examination Survey (NHANES) III, a representative sample of US noninstitutionalized adults, in which participants were surveyed from 1988 to 1994. The frequency of hot red chili pepper consumption was measured in 16,179 participants at least 18 years of age. Total and cause-specific mortality were the main outcome measures. During 273,877 person-years of follow-up (median 18.9 years), a total of 4,946 deaths were observed. Total mortality for participants who consumed hot red chili peppers was 21.6% compared to 33.6% for those who did not (absolute risk reduction of 12%; relative risk of 0.64). Adjusted for demographic, lifestyle, and clinical characteristics, the hazard ratio was 0.87 (P = 0.01; 95% Confidence Interval 0.77, 0.97). Consumption of hot red chili peppers was associated with a 13% reduction in the instantaneous hazard of death. Similar, but statistically nonsignificant trends were seen for deaths from vascular disease, but not from other causes. In this large population-based prospective study, the consumption of hot red chili pepper was associated with reduced mortality. Hot red chili peppers may be a beneficial component of the diet.”

lroot on January 10th, 2017

Walking my way to 100

Like everything else in the body, the white-matter fibers that allow communication between brain regions also decline with age. In a new study, researchers found a strong association between the structural integrity of these white-matter tracts and an older person’s level of daily activity not just the degree to which the person engaged in moderate or vigorous exercise, but also whether he or she was sedentary the rest of the time.

The study, reported in the journal PLOS ONE, tracked physical activity in 88 healthy but “low-fit” participants aged 60 to 78. The participants agreed to wear accelerometers during most of their waking hours over the course of a week, and also submitted to brain imaging.

“To our knowledge, this is the first study of its kind that uses an objective measure of physical activity along with multiple measures of brain structure,” said University of Illinois postdoctoral researcher Agnieszka Burzynska, who conducted the research with U. of I. Beckman Institute director Arthur Kramer and kinesiology and community health professor Edward McAuley.

Most studies ask subjects to describe how much physical activity they get, which is subjective and imprecise, Burzynska said. The accelerometer continuously tracks a person’s movement, “so it’s not what they say they do or what they think they do, but we have measured what they are actually doing,” she said.

The researchers assumed that participants’ activity levels over a week accurately reflected their overall engagement, or lack of engagement, in physical activity.

The study also relied on two types of brain imaging. The first, diffusion tensor imaging, offers insight into the structural integrity of a tissue by revealing how water is diffused in the tissue. The second method looks for age-related changes in white matter, called lesions. Roughly 95 percent of adults aged 65 and older have such lesions, Burzynska said. While they are a normal part of aging, their early onset or rapid accumulation may spell trouble, she said.

The team found that the brains of older adults who regularly engaged in moderate-to-vigorous exercise generally “showed less of the white-matter lesions,” Burzynska said.

The association between physical activity and white-matter structural integrity was region-specific, the researchers reported. Older adults who engaged more often in light physical activity had greater structural integrity in the white-matter tracts of the temporal lobes, which lie behind the ears and play a key role in memory, language, and the processing of visual and auditory information.

In contrast, those who spent more time sitting had lower structural integrity in the white-matter tracts connecting the hippocampus, “a structure crucial for learning and memory,” Burzynska said.

“This relationship between the integrity of tracts connecting the hippocampus and sedentariness is significant even when we control for age, gender and aerobic fitness,” she said. “It suggests that the physiological effect of sitting too much, even if you still exercise at the end of the day for half an hour, will have a detrimental effect on your brain.”

The findings suggest that engaging in physical activity and avoiding a sedentary lifestyle are both important for brain health in older age, Burzynska said.

“We hope that this will encourage people to take better care of their brains by being more active,” she said.

Reference: Agnieszka Zofia Burzynska ,Laura Chaddock-Heyman,Michelle W. Voss,Chelsea N. Wong,Neha P. Gothe,Erin A. Olson,Anya Knecht,Andrew Lewis,Jim M. Monti,Gillian E. Cooke,Thomas R. Wojcicki,Jason Fanning,Hyondo David Chung,Elisabeth Awick,Edward McAuley,Arthur F. Kramer. Physical Activity and Cardiorespiratory Fitness Are Beneficial for White Matter in Low-Fit Older Adults. PLoS ONE 9(9): e107413. doi:10.1371/journal.pone.0107413

lroot on January 9th, 2017

healthy-teeth

The stem cells in our teeth can be energized to fill in chips, cracks, and cavities, researchers say, and the findings could one day possibly make dental cement obsolete.

The work has been conducted just in mice so far, but the research, published Monday in the journal Scientific Reports, highlights a way to motivate stem cells to repair tooth defects at a scale they normally can’t, with a drug that already has some safety testing behind it. It also demonstrates the potential of a type of stem cell therapy in which the cells are stimulated in place, rather than taken out, manipulated, and put back in.

“We’re mobilizing stem cells in the body and it works,” said Paul Sharpe, a researcher at King’s College London and an author of the new paper. “If it works for teeth, chances are it could work for other organs.”

Experts not involved with the work noted that while it is in early stages, the simplicity of the approach should ease its path into the next phases of research that show whether it might produce the same results in people.

“These important steps close down the translational gap and bring this discovery a step closer to future clinical applications,” Dr. Vanessa Chrepa, a researcher at the University of Washington, wrote in an email. “This work will hopefully set the stage for clinical studies in the near future.”

When teeth lose some of their dentin — the bony tissue beneath the enamel that makes up the bulk of the tooth — the stem cells tucked deep inside mount a recovery effort and manufacture new dentin (which is also spelled dentine). The problem, Sharpe said, is that the natural repair mechanism can only regrow small amounts of dentin and can’t make up all that is lost when a tooth suffers a serious injury, contracts a major infection, or takes on the sharp end of a dentist’s drill.

Because of the limits of the teeth’s ability to repair themselves, dentists have to fill or seal teeth to prevent further infection and degradation. But dental cement also prevents the tooth from ever returning to its natural, pearly white self.

Sharpe and his team have been trying to understand how the natural repair mechanism works in hopes of converting that understanding into a way to super-power it. As part of their research, they discovered that a group of molecules called glycogen synthase kinase inhibitors (or GSK-3 inhibitors) boosts the stem cells’ ability to stimulate production of dentin beyond what normally occurs.

For the new study, the researchers drilled tiny holes into mice’s molars to expose the tooth’s pulp, where the stem cells live. They then inserted collagen sponges that had been soaked in one of three types of GSK-3 inhibitors and covered the tooth.

After six weeks, the researchers removed the teeth and found that the sponges had dissolved and the lost dentin had mostly been regenerated.

“They’ve harnessed the signaling pathway that promotes natural repair,” said Megan Pugach, a researcher at the Forsyth Institute in Cambridge, Mass., and at the Harvard School of Dental Medicine, who was not involved with the research.

Sharpe and his team are now conducting similar studies in rats to make sure the approach can generate enough dentin to fill in larger holes in larger teeth before trying to study the method in people. But two aspects of the approach could help ease its path into clinical trials.

mediterranean-diet

A new study shows that older people who followed a Mediterranean diet retained more brain volume over a three-year period than those who did not follow the diet as closely. The study is published in the January 4, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. But contrary to earlier studies, eating more fish and less meat was not related to changes in the brain.

The Mediterranean diet includes large amounts of fruits, vegetables, olive oil, beans, whole grains, moderate amounts of fish, dairy and wine, and limited red meat and poultry.

“As we age, the brain shrinks and we lose brain cells which can affect learning and memory,” said study author Michelle Luciano, PhD, of the University of Edinburgh in Scotland. “This study adds to the body of evidence that suggests the Mediterranean diet has a positive impact on brain health.”

Researchers gathered information on the eating habits of 967 Scottish people around age 70 who did not have dementia. Of those people, 562 had an MRI brain scan around age 73 to measure overall brain volume, gray matter volume and thickness of the cortex, which is the outer layer of the brain. From that group, 401 people then returned for a second MRI at age 76. These measurements were compared to how closely participants followed the Mediterranean diet.

The participants varied in how closely their dietary habits followed the Mediterranean diet principles. People who didn’t follow as closely to the Mediterranean diet were more likely to have a higher loss of total brain volume over the three years than people who followed the diet more closely. The difference in diet explained 0.5 percent of the variation in total brain volume, an effect that was half the size of that due to normal aging.

The results were the same when researchers adjusted for other factors that could affect brain volume, such as age, education and having diabetes or high blood pressure.

There was no relationship between grey matter volume or cortical thickness and the Mediterranean diet.

The researchers also found that fish and meat consumption were not related to brain changes, which is contrary to earlier studies.

“It’s possible that other components of the Mediterranean diet are responsible for this relationship, or that it’s due to all of the components in combination,” Luciano said.

Luciano noted that earlier studies looked at brain measurements at one point in time, whereas the current study followed people over time.

“In our study, eating habits were measured before brain volume was, which suggests that the diet may be able to provide long-term protection to the brain,” said Luciano. “Still, larger studies are needed to confirm these results.”

Reference: 1.Michelle Luciano, Janie Corley, Simon R. Cox, Maria C. Valdés Hernández, Leone C.A. Craig, David Alexander Dickie, Sherif Karama, Geraldine M. McNeill, Mark E. Bastin, Joanna M. Wardlaw, Ian J. Deary. Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort. Neurology, 2017; 10.1212/WNL.0000000000003559 DOI: 10.1212/WNL.0000000000003559