Soluble Corn Fiber Helps Build and Protect Bone

Corn

Supplementing with soluble corn fiber can help build and retain calcium in bone, according to new research from Purdue University. The study focused on two critical times in a woman’s life adolescence and post-menopause, however the results may be beneficial to all adolescents and adults regardless of age.

“We are looking deeper in the gut to build healthy bone in girls and help older women retain strong bones,” said Connie Weaver, distinguished professor and head of nutrition science. “Soluble corn fiber, a prebiotic, helps the body better utilize calcium during both adolescence and post-menopause. The gut microbiome is the new frontier in health.”

The post-menopause findings are published in the American Journal of Clinical Nutrition, and the adolescent findings are published in Journal of Nutrition. The studies are funded by Tate & Lyle Ingredients America LLC. Weaver serves on the scientific advisory board for Pharmative LLC.

A prebiotic fiber passes through the gut for the microbes in the lower gut to digest. Here is where Weaver found that soluble corn fiber is broken down into short chain fatty acids to aid in bone health.

In the post-menopausal study, calcium retention was measured in 14 women by using an isotope to measure the excretion of 41Ca to measure bone loss. The women consumed 0 grams, 10 grams or 20 grams of this nondigestible carbohydrate each day for 50 days. Bone calcium retention was improved by 4.8 percent and 7 percent for those who consumed 10 grams and 20 grams, respectively. These amounts of soluble corn fiber would be found in supplement form.

“If projected out for a year, this would equal and counter the average rate of bone loss in a post-menopausal woman,” said Weaver, an expert in mineral bioavailability, calcium metabolism, botanicals and bone health.

The calcium 41 technology, an isotope measure to trace calcium deposits through accelerator mass spectrometry in the Purdue Rare Isotope Measurement Laboratory (PRIME Lab), can measure atomic quantities. In the adolescent study, 44Ca and 43Ca were used.

Thirty-one girls either consumed 0 grams, 10 grams or 20 grams of soluble corn fiber carbohydrate each day for three weeks while maintaining their regular diets. Both 10 grams and 20 grams led to improved calcium absorption by 12 percent for female adolescents, which would build 1.8 percent more skeleton a year.

In both studies, gastrointestinal symptoms were minimal and the same for the control groups, as well as in those who consumed soluble corn fiber.

“Most studies looking at benefits from soluble corn fiber are trying to solve digestion problems, and we are the first to determine that this relationship of feeding certain kind of fiber can alter the gut microbiome in ways that can enhance health,” Weaver said. “We found this prebiotic can help healthy people use minerals better to support bone health.”

Calcium is considered a shortfall nutrient, and few people meet the recommended intake of 1,300 milligrams of calcium for healthy bone mass.

“The finding doesn’t mean we should diminish our recommendation to consume calcium and follow a well-balanced diet. This is a strategy to better utilize your minerals,” Weaver said. “Calcium alone suppresses bone loss, but it doesn’t enhance bone formation. These fibers enhance bone formation, so they are doing something more than enhancing calcium absorption.”

Weaver’s team is looking into the mechanisms of how soluble corn fiber boosts calcium absorption and retention, as well as if the prebiotic fiber benefits the body in other ways.

Soluble Corn Fiber can be purchased at many health food stores.

References:

S. A. Jakeman, C. N. Henry, B. R. Martin, G. P. McCabe, L. D. McCabe, G. S. Jackson, M. Peacock, C. M. Weaver. Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial. American Journal of Clinical Nutrition, 2016; doi: 10.3945/ajcn.116.132761

Corrie M Whisner, Berdine R Martin, Cindy H Nakatsu, Jon A Story, Claire J MacDonald-Clarke, Linda D McCabe, George P McCabe, and Connie M Weaver. Soluble Corn Fiber Increases Calcium Absorption Associated with Shifts in the Gut Microbiome: A Randomized Dose-Response Trial in Free-Living Pubertal Females. J. Nutr. jn227256; 2016; doi: 10.3945/jn.115.227256

Fasting Promotes Stem Cell Regeneration

Adult Stem Cells

Fasting as little as eight days a year could help bodies become healthier, according to new research from the University of Southern California.

Fasting two to four days at a time every six months causes stem cells to awake from their normal dormant state, and start regenerating. Researchers discovered this practice eliminated damaged and older cells, and caused new cells to be born, effectively renewing the immune system. This is the first time any natural intervention has ever been shown to trigger this self-renewal.

In mice and humans, white blood cell counts were significantly lowered after long periods without food. These bodies are vital to the human immune system. But, when their numbers decline to a critical point, pathways for hematopoietic stem cells were switched on. These cells manage the immune system and generate new blood.

“When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged,” Valter Longo of the USC Davis School of Gerontology, said.

Going without food for 48 to 96 hours shifts human bodies to consume stores of fat, glucose (sugar), and ketones (created when fats are broken down for energy). Unhealthy white blood cells are also broken down, so that their components can be reused for the next generation of cells. This process is akin to recycling for the immune system.

After a period of fasting, human immune systems generate new blood cells when nutrients start flowing back into the body. Researchers at USC wanted to know what drives body systems to rebuild the cells.

Protein kinase A, an enzyme known to inhibit cell regeneration, was reduced in the systems of people who are fasting, the study found. Concentrations of a growth-factor hormone called IGF-1 were also lowered in those who have not eaten in days.

Of course most people would not want to fast on only water for two to four days at a time and it is probably not safe except under medical supervision. There are several alternatives that produce some of the same benefits including juice fasting and time restricted eating for people that are healthy enough to do a less extreme form of fasting.

Juice fasting involves drinking raw fruit and vegetable juices usually for one day at a time. Some people juice fast once a week and others once a month. It is important to use at least 50% vegetables to make juice and not overdue the fructose sugars that are concentrated in fruit juice. Typically between 2 and 3 quarts of juice are consumed per day. There are now many brands of pressure pasteurized juices available in health food stores that are raw. High pressure is used to destroy the bacteria instead of heat. Water is not restricted on a juice fast.

Another approach to fasting which has produced beneficial results is time restricted eating. It involves eating with no limit on quantity during an 8 hour consecutive period and then going without food until the next day. Water is available to drink 24 hours each day and not restricted. Some people eat this way every day. A scientific study of time restricted eating which showed impressive results was published in Cell Metablolism.

Reference: Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression. Cell Stem Cell, Volume 14, Issue 6, p810?823, 5 June 2014

Meditation Improves the Brain’s Physical Structure

Meditation

Several years ago, researchers at UCLA found that specific regions in the brains of long-term meditators were larger and had more gray matter than the brains of individuals in a control group. This suggested that meditation may indeed be good for all of us since, alas, our brains shrink naturally with age.

Now, a follow-up study suggests that people who meditate also have stronger connections between brain regions and show less age-related brain atrophy. Having stronger connections influences the ability to rapidly relay electrical signals in the brain. And significantly, these effects are evident throughout the entire brain, not just in specific areas.

Eileen Luders, a visiting assistant professor at the UCLA Laboratory of Neuro Imaging, and colleagues used a type of brain imaging known as diffusion tensor imaging, or DTI, a relatively new imaging mode that provides insights into the structural connectivity of the brain. They found that the differences between meditators and controls are not confined to a particular core region of the brain but involve large-scale networks that include the frontal, temporal, parietal and occipital lobes and the anterior corpus callosum, as well as limbic structures and the brain stem.

“Our results suggest that long-term meditators have white-matter fibers that are either more numerous, more dense or more insulated throughout the brain,” Luders said. “We also found that the normal age-related decline of white-matter tissue is considerably reduced in active meditation practitioners.”

The study consisted of 27 active meditation practitioners (average age 52) and 27 control subjects, who were matched by age and sex. The meditation and the control group each consisted of 11 men and 16 women. The number of years of meditation practice ranged from 5 to 46; self-reported meditation styles included Shamatha, Vipassana and Zazen, styles that were practiced by about 55 percent of the meditators, either exclusively or in combination with other styles.

Results showed pronounced structural connectivity in meditators throughout the entire brain’s pathways. The greatest differences between the two groups were seen within the corticospinal tract (a collection of axons that travel between the cerebral cortex of the brain and the spinal cord); the superior longitudinal fasciculus (long bi-directional bundles of neurons connecting the front and the back of the cerebrum); and the uncinate fasciculus (white matter that connects parts of the limbic system, such as the hippocampus and amygdala, with the frontal cortex).

“It is possible that actively meditating, especially over a long period of time, can induce changes on a micro-anatomical level,” said Luders, herself a meditator.

As a consequence, she said, the robustness of fiber connections in meditators may increase and possibly lead to the macroscopic effects seen by DTI.

“Meditation, however, might not only cause changes in brain anatomy by inducing growth but also by preventing reduction,” Luders said. “That is, if practiced regularly and over years, meditation may slow down aging-related brain atrophy, perhaps by positively affecting the immune system.”

But there is a “but.” While it is tempting to assume that the differences between the two groups constitute actual meditation-induced effects, there is still the unanswered question of nature versus nurture.

“It’s possible that meditators might have brains that are fundamentally different to begin with,” Luders said. “For example, a particular brain anatomy may have drawn an individual to meditation or helped maintain an ongoing practice — meaning that the enhanced fiber connectivity in meditators constitutes a predisposition towards meditation, rather than being the consequence of the practice.”

Still, she said, “Meditation appears to be a powerful mental exercise with the potential to change the physical structure of the brain at large. Collecting evidence that active, frequent and regular meditation practices cause alterations of white-matter fiber tracts that are profound and sustainable may become relevant for patient populations suffering from axonal demyelination and white-matter atrophy.”

While the study looked at more traditional meditation there is also evidence from other studies that similar improvements may apply to moving forms such as Tai Chi, Qigong and Shen Zhen.

Reference: Luders E., Clark K., Narr K. L., Toga A. W. (2011). Enhanced brain connectivity in long-term meditation practitioners. Neuroimage 57, 1308?1316. 10.1016/j.neuroimage.2011.05.075

How much exercise makes up for sitting all day?

Walking my way to 100

Last year a study showed that sitting continuously for one hour or more was unhealthy. Now a newer and more extensive study of data of over 1 million individuals specifically looked at how much exercise is needed to counter the negative effects of sitting. According to an international team of researchers the health risks associated with sitting for eight or more hours a day whether at work, home or commuting can be eliminated with an hour or more of physical activity a day.

Ever since a study back in 1953 discovered that London bus drivers were at greater risk of heart disease compared to bus conductors, scientists have found increasing evidence that lack of physical activity is a major risk factor for several diseases and for risk of early death. Recent estimates suggest that more than 5 million people die globally each year as a result of failing to meet recommended daily activity levels.

Studies in high-income countries have suggested that adults spend the majority of their waking hours sitting down. A typical day for many people is driving to work, sitting in an office, driving home and watching TV. Current physical activity guidelines recommend that adults do at least 150 minutes of moderate intensity exercise per week. But, is that enough?

In an analysis published today in The Lancet that draws together a number of existing studies, an international team of researchers asked the question: if an individual is active enough, can this reduce, or even eliminate, the increased risk of early death associated with sitting down?

In total the researchers analysed 16 studies, which included data from more than one million men and women. The team grouped individuals into four quartiles depending on their level of moderate intensity physical activity, ranging from less than 5 minutes per day in the bottom group to over 60 minutes in the top. Moderate intensity exercise was defined as equating to walking at 3.5 miles/hour or cycling at 10 miles/hour, for example.

The researchers found that 60 to 75 minutes of moderate intensity exercise per day were sufficient to eliminate the increased risk of early death associated with sitting for over eight hours per day. However, as many as three out of four people in the study failed to reach this level of daily activity.

The greatest risk of early death was for those individuals who were physically inactive, regardless of the amount of time sitting — they were between 28% and 59% more likely to die early compared with those who were in the most active quartile — a similar risk to that associated with smoking and obesity. In other words, lack of physical activity is a greater health risk than prolonged sitting.

“There has been a lot of concern about the health risks associated with today’s more sedentary lifestyles,” says Professor Ulf Ekelund from the Medical Research Council Epidemiology Unit at the University of Cambridge. “Our message is a positive one: it is possible to reduce — or even eliminate — these risks if we are active enough, even without having to take up sports or go to the gym.

“For many people who commute to work and have office-based jobs, there is no way to escape sitting for prolonged periods of time. For these people in particular, we cannot stress enough the importance of getting exercise, whether it’s getting out for a walk at lunchtime, going for a run in the morning or cycling to work. An hour of physical activity per day is the ideal, but if this is unmanageable, then at least doing some exercise each day can help reduce the risk.”

The researchers acknowledge that there are limitations to the data analyzed, which mainly came from participants aged 45 years and older and living in western Europe, the US and Australia. However, they believe that the strengths of the analysis outweigh these limitations. Most importantly, the researchers asked all included studies to reanalyze their data in a harmonized manner, an approach that has never before been adopted for a study of this size and therefore also provides much more robust effect estimates compared with previous studies.

Reference: Ulf Ekelund, Jostein Steene-Johannessen, Wendy J Brown, Morten Wang Fagerland, Neville Owen, Kenneth E Powell, Adrian Bauman, I-Min Lee. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. The Lancet, 2016; DOI: 10.1016/S0140-6736(16)30370-1

Nanog Gene Reverses Aging in Adult Stem Cells

Nanog Gene

The ability to reverse aging may reside in a stem cell gene named Nanog.

In a series of experiments at the University at Buffalo, the gene kicked into action dormant cellular processes that are key to maintaining healthy bones, arteries and other telltale signs of growing old.

The findings, published June 29 in the journal Stem Cells, also show promise in counteracting premature aging disorders.

“Our research into Nanog is helping us to better understand the process of aging and ultimately how to reverse it,” says Stelios T. Andreadis, PhD, professor and chair of the Department of Chemical and Biological Engineering at the UB School of Engineering and Applied Sciences, and the study’s lead author.

Additional authors come from UB’s Department of Biomedical Engineering, a joint program between UB’s engineering school and the Jacobs School of Medicine and Biomedical Sciences at UB, and the Department of Biostatistics and Bioinformatics at Roswell Park Cancer Institute in Buffalo.

To battle aging, the human body holds a reservoir of nonspecialized cells that can regenerate organs. These cells are called adult stem cells, and they are located in every tissue of the body and respond rapidly when there is a need.

But as people age, fewer adult stem cells perform their job well, a scenario which leads to age-related disorders. Reversing the effects of aging on adult stem cells, essentially rebooting them, can help overcome this problem.

Andreadis previously showed that the capacity of adult stem cells to form muscle and generate force declines with aging. Specifically, he examined a subcategory of muscle cells called smooth muscle cells which reside in arteries, intestines and other tissues.

In the new study, Panagiotis Mistriotis, a graduate student in Andreadis’ lab and first author of the study, introduced Nanog into aged stem cells. He found that Nanog opens two key cellular pathways: Rho-associated protein kinase (ROCK) and Transforming growth factor beta (TGF-?).

In turn, this jumpstarts dormant proteins (actin) into building cytoskeletons that adult stem cells need to form muscle cells that contract. Force generated by these cells ultimately helps restore the regenerative properties that adult stem cells lose due to aging.

“Not only does Nanog have the capacity to delay aging, it has the potential in some cases to reverse it,” says Andreadis, noting that the embryonic stem cell gene worked in three different models of aging: cells isolated from aged donors, cells aged in culture, and cells isolated from patients with Hutchinson-Gilford progeria syndrome.

Additionally, the researchers showed that Nanog activated the central regulator of muscle formation, serum response factor (SRF), suggesting that the same results may be applicable for skeletal, cardiac and other muscle types.

The researchers are now focusing on identifying drugs that can replace or mimic the effects of NANOG. This will allow them to study whether aspects of aging inside the body can also be reversed. This could have implications in an array of issues to improve quality of life and lifespan.

Reference: Mistriotis, P., Bajpai, V. K., Wang, X., Rong, N., Shahini, A., Asmani, M., Liang, M.-S., Wang, J., Lei, P., Liu, S., Zhao, R. and Andreadis, S. T. (2016), NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression. STEM CELLS. doi: 10.1002/stem.2452

Vibrating Stem Cells Create New Bone

Stem Cells Grow Bone

New treatments for osteoporosis or broken bones are on the horizon after scientists discovered they can grow new bone simply by vibrating stem cells.

Currently the only option for patients who suffer complicated breaks is to undergo painful surgery where doctors remove bone from a healthy part of their body and transplant it in the damaged site.

But now Scottish scientists have discovered that stem cells can be coaxed into turning into bone cells ? known as osteoblasts ? using low frequency vibrations in the lab, a technique dubbed ?nanokicking.?

Stem cells are thought to be the future of medicine because they can become any cell in the body depending on their environment.

Researchers at the University of West Scotland and the University of Glasgow believe that the 1000Hz frequency mimics conditions experienced by natural bone in the body and induces stem cells to turn into bone in around 28 days, which can then be implanted.

The scientists also hope the same frequency could be used to encourage healing from within the body without the need for a transplant.

?Our bodies are continuously experiencing mechanical stimuli, such as from our walking steps and our heart beat,? said Professor Stuart Reid of the University of West Scotland.

?We know that natural bone has some interesting mechanoelectrical properties, the piezoelectric effect – converting mechanical stress to electricity, which are optimal close to 1000Hz.

?It is also well known that bone can only remain healthy when it is actively being loaded, hence why astronauts lose bone mass when in space. So we believe that we are mimicking something that the cells experience in our bodies, however the exact details are still being untangled.?

Bone is the second most commonly transplanted tissue in the world, behind blood transplants, and is used in many common procedures.

The UK?s aging population means demand is increasing due to conditions such as osteoporosis and hip fractures.

Using a patient?s own stem cells to build new bone would mean there was no risk of rejection. The stem cells could be retrieved from a patient?s bone marrow or even from fat cells from liposuction.

The stem cells are ?jiggled? in petri dishes on a specially built vibrating platform called a bioreactor which uses the same technology that astrophysicists use to hunt for gravitational waves ? the distortions in space time which occur when black holes collide.

Professor Matt Dalby, of the University of Glasgow said: ?The bioreactor we have designed brings together fields of research from different ends of the spectrum: stem cell research on the building blocks of our bodies, to technology used to detect the ripples in space and time caused by the collisions of massive objects.

?It?s amazing that technology developed to look for gravitational waves has a down-to-earth application in revolutionizing bone treatments for cleaner, safer and more effective therapy.?

Prof Reid, added: ?The scale of movement that triggers the cells to transform is so small it would be the same as ?sliding a single sheet of paper in and out from under a football on a table?.?

The team aims to test their lab-grown bone in people within 3 years and that therapy could be available in 10 years.

Further down the line they hope it will be possible to stimulate stem cells directly to heal fractures without surgery.

Avoid Saturated and Trans Fats For Health and Long Life

Healthy Fats

Consuming higher amounts of unsaturated fats was associated with lower mortality, according to a study from Harvard T.H. Chan School of Public Health. In a large study population followed for more than three decades, researchers found that higher consumption of saturated and trans fats was linked with higher mortality compared with the same number of calories from carbohydrates. Most importantly, replacing saturated fats with unsaturated fats conferred substantial health benefits. This study provides further support for the 2015-2020 Dietary Guidelines for Americans that emphasize the types of fat rather than total amount of fat in the diet.

The study is the most detailed and powerful examination to date on how dietary fats impact health. It suggests that replacing saturated fats like butter, lard, and fat in red meat with unsaturated fats from plant-based foods — like olive oil, nuts, seeds, and avocados — can confer substantial health benefits and should continue to be a key message in dietary recommendations. Coconut oil is a type of saturated fat, however it has a different molecular structure than animal fats so the study does not apply to it.

“There has been widespread confusion in the biomedical community and the general public in the last couple of years about the health effects of specific types of fat in the diet,” said Dong Wang, a doctoral candidate, SD ’16, in the Departments of Nutrition and Epidemiology at Harvard Chan School and lead author of the study. “This study documents important benefits of unsaturated fats, especially when they replace saturated and trans fats.”

The study included 126,233 participants from two large long-term studies — the Nurses’ Health Study and the Health Professionals Follow-Up Study — who answered survey questions every 2-4 years about their diet, lifestyle, and health for up to 32 years. During the follow-up, 33,304 deaths were documented. Researchers from Harvard Chan School and Brigham and Women’s Hospital examined the relationship between types of fats in the participants’ diets and overall deaths among the group during the study period.

Different types of dietary fat had different associations with mortality, the researchers found. Trans fats–on their way to being largely phased out of food — had the most significant adverse impact on health. Every 2% higher intake of trans fat was associated with a 16% higher chance of premature death during the study period. Higher consumption of saturated fats was also linked with greater mortality risk. When compared with the same number of calories from refined carbohydrate, every 5% increase in saturated fat intake was associated with an 8% higher risk of overall mortality.

Conversely, intake of unsaturated fats — both polyunsaturated and monounsaturated — was associated with between 11% and 19% lower overall mortality compared with the same number of calories from refined carbohydrates. Among the polyunsaturated fats, both omega-6, found in most plants, and omega-3 fatty acids, found in fish and flax seeds, were associated with lower risk of premature death.

The health effects of specific types of fats depended on what people were replacing them with, the researchers found. For example, people who replaced saturated fats with unsaturated fats had significantly lower risk of death overall during the study period compared with those who maintained high intakes of saturated fats. The findings are consistent with many earlier studies showing reduced total and LDL (“bad”) cholesterol when unsaturated fats replace trans or saturated fats.

People who replaced saturated fats with refined carbohydrates had only slightly lower mortality risk. In addition, replacing total fat with refined carbohydrates was associated with modestly higher mortality. This was not surprising, the authors said, because carbohydrates in the American diet tend to be primarily refined starch and sugar, which have a similar influence on mortality risk as saturated fats.

“Our study shows the importance of eliminating trans fat and replacing saturated fat with unsaturated fats.” said senior author Frank Hu, professor of nutrition and epidemiology at Harvard Chan School and professor of medicine at Harvard Medical School. In practice, this can be achieved by replacing excessive saturated fat from animal sources with a variety of fats from vegetable sources and cold water fish such as avocados, olives, nuts, seeds, and wild salmon. This does not mean becoming a vegetarian only reducing animal fat consumption. Finding sources of meat that are from 100% grass/pasture fed animals which have a much lower fat content is also a good idea. Modern ranching where animals are fed a diet high in grain and soy produces meat that is many times higher in saturated fat which is much of the problem.

Tai Chi and Brisk Walking Increase Stem Cells

Stem Cells

Tai Chi has been shown to have many great health benefits. However, few research attempts have been made to explore the effects of practicing TCC on life span. A study published in Cell Transplantation provides direct evidence of Tai Chi?s anti-aging effects. The study compared the rejuvenating and anti-aging effects among a Tai Chi group, a brisk walking group, and a no exercise group. Thirty-two participants were selected based on a survey of their activity level during the previous year so that each fit into one of the three groups.

The CD34+ stem cell counts in peripheral blood of the participants was determined, and the Kruskal Wallis test was used to evaluate and compare the anti-aging effects of the three groups. Of the 32 participants in this study, the participants in the Tai Chi group (10 participants) had a significantly higher number of CD 34+ stem cells than the no exercise group (12 participants). No significant difference was found between the Tai Chi group and the brisk walking group. Tai Chi practice sustained for more than 1 year may be an intervention against aging as effective as brisk walking in terms of its benefits on the improvement of the number of CD34+ stem cells.

CD 34+ cells express the CD 34 protein and are “cluster markers” for hematopoietic stem cells (blood stem cells) involved in cell self-renewal, differentiation and proliferation.

“It is possible that Tai Chi may prompt vasodilation and increase blood flow,” said study corresponding author Dr. Shinn-Zong Lin of the Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan. “Considering that brisk walking may require a larger space or more equipment, Tai Chi seems to be an easier and more convenient choice of anti-aging exercise.”

“This study provides the first step into providing scientific evidence for the possible health benefits of Tai Chi.” said Dr. Paul R. Sanberg, distinguished professor at the Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL. “Further study of how Tai Chi can elicit benefit in different populations and on different parameters of aging are necessary to determine its full impact.”

Hearing and the Atoh1 Gene

Non-mammals such as birds can recover from deafness as quickly as humans can recover from a cut or bruise. In contrast, when humans and other mammals sustain damage to the inner ear’s sensory cells, the resulting hearing loss is permanent.

In two studies published in the journal Development, researchers from the USC Stem Cell laboratory of Neil Segil examined how a key gene, called Atoh1, underpins the development and potential regeneration of the inner ear’s sensory cells, which are known as hair cells.

In the first study, researchers Zlatka P. Stojanova, Tao Kwan and Segil explored how Atoh1 is either “turned on” or “turned off” through a process called epigenetic regulation. By studying the mouse inner ear, the team documented the precise epigenetic signals that turn on or “upregulate” Atoh1 in the progenitor cells that become hair cells during embryonic development, and the epigenetic signals that turn off or “downregulate” Atoh1 during the first week after birth–when the newborn mouse loses its potential to regenerate hair cells and recover from hearing loss.

In the second study, researchers Yassan Abdolazimi, Stojanova and Segil showed that a group of genes called Hes/Hey directly interact with and repress Atoh1 to sculpt the developing structure in the inner ear called the organ of Corti into a complex mosaic of different cell types that ultimately enables hearing.

“These two studies advance our understanding of both the genetic and epigenetic signals that regulate Atoh1, a critical factor in the development of hair cells and the entire sensory structure,” said Segil, professor of research in the Department of Stem Cell Biology and Regenerative Medicine, and the USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery. “In the future, we hope to find drugs that target these genetic and epigenetic regulators of Atoh1, and that might provide new therapies to stimulate hair cell regeneration in individuals with hearing loss or deafness.”

Stress Associated With Decrease In Longevity Hormone

Women under chronic stress have significantly lower levels of klotho, a hormone that regulates aging and enhances cognition according to researchers at the University of California in San Francisco. They conducted a study that compared mothers of children on the autism spectrum to low-stress controls.

The researchers also found that the women with clinically significant depressive symptoms had even lower levels of klotho in their blood than those who were under stress but not experiencing such symptoms.

The study, published in Translational Psychiatry, is the first to show a relationship between psychological influences and klotho, which performs a wide variety of functions in the body.

“Our findings suggest that klotho, which we now know is very important to health, could be a link between chronic stress and premature disease and death,” said lead author, Aric Prather, PhD, an assistant professor of psychiatry at UCSF. “Since our study is observational, we cannot say that chronic stress directly caused lower klotho levels, but the new connection opens avenues of research that converge upon aging, mental health, and age-related diseases.”

Scientists know from their work in mice and worms that, when klotho is disrupted, it promotes symptoms of aging, such as hardening of the arteries and the loss of muscle and bone, and when klotho is made more abundant, the animals live longer.

In previous work, senior author Dena Dubal, MD, PhD, showed that a genetic variant carried by one in five people is associated with having more klotho in the bloodstream, better cognitive function and a larger region of the prefrontal cortex. Carriers also tend to live longer and have lower rates of age-related disease. Dubal and colleagues found that increasing klotho in mice boosted their cognition and increased resilience to toxins, suggesting a therapeutic role for klotho in the brain.

The current study included 90 high-stress caregivers and 88 low-stress controls, most of whom were in their 30s and 40s and otherwise healthy. Klotho is known to decline with age, but in this cross-sectional study of relatively young women, this decline only happened among the high-stress women. The low-stress women did not show a significant reduction in klotho with aging.

“Chronic stress transmits risk for bad health outcomes in aging” said Dubal, an assistant professor in the UCSF Department of Neurology and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease. “It will be important to figure out if higher levels of klotho can benefit mind and body health as we age. If so, therapeutics or lifestyle interventions that increase the longevity hormone could have a big impact on people’s lives.”

The researchers hypothesized that lower levels of klotho could contribute to stress and depression, since klotho acts on a variety of cellular, molecular and neural pathways that link to stress and depression.