In a research area that will generate blockbuster profits if/when it pans out, a science team reported creating new hair cells from pluripotent stem cells in a recent issue of PLOS (Proceedings of the Library of Science) One.

The team, led by the Sanford Burnham Medical Research Institute, got their results using two different kinds of cells: embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. ES cells can form all body cells. IPS cells can, as well. The difference is iPS cells are derived from adult cells, not in vitro fertilization (IVF) clinic embryos. The clock is turned back on the adult cells, until they reach a pluripotent state like that of ES cells.

?The relative simplicity of the procedure to derive [dermal-papilla]-like cells was a pleasant surprise,? Sanford Burnham developmental biologist Alexey Terskikh told Drug Discovery & Development. Terskikh is senior author on the paper. ?To the best of my knowledge, we are the first team to report the generation of hair inducing cells? from embryonic stem cells. ?The most critical next step is to investigate whether this approach works in humans.?

The new approach

Terskikh?s group believes their creation of neural crest cells from ES cells, which then formed dermal papilla cells, was a key step. Dermal papilla cells regulate hair-follicle formation and growth cycle. Limited adult dermal papilla (DP) cells do not work as hair transplants as they generally can?t be obtained in the large amounts, and can quickly lose hair-follicle forming ability in culture.

But neural crest cells transiently arise from the dorsal neural tube during development, and give rise to many tissues at that time, including hair follicle cells. So Terskikh?s group first worked on persuading their pluripotent cells to become neural crest cells. Human ES cells ?have been directed to various cell fates including hair follicle epidermal cells?keratinocytes; however, the derivation of DP cells have not been reported? from ES cells, the team wrote. ?Here we describe for the first time the derivation of functional DP-like cells human embryonic stem cells.?

Alexey Terskikh, Ph.D, the Sanford Burnham Medical Research Institute developmental biologist behind a recent effort to create hair cells from stem cells Alexey Terskikh, Ph.D, the Sanford Burnham Medical Research Institute developmental biologist behind a recent effort to create hair cells from stem cells The group reported their human ES-cell derived neural crest cells, cultured in serum, progressively acquired the markers of DP cells, and gave rise to cell populations with ?robust? hair-inducing potential in mice. They speculated the superior hair-creation capacity of their pluripotent cell derived DPs to most reported adult DPs may have to do with the resemblance of their cells to embryonic or neonatal DP precursor cells.

The group also reported their cells are heterogeneous, a ?mixed population? of neural-crest-derived cells that ?contain DP-like cells with hair-inducing properties, but also might contain melanocyte- and keratinocyte-forming cells.? Therefore, ?further analysis?is needed to address this question.?

The group also noted they had more success with human ES cells than with human IPS cells. They only achieved hair cells with one of three iPS cell lines. However, if many lines are used, hair cells should ultimately result, they wrote.

Overall, the group reported, ?our results suggest that the intermediate step of hESC differentiation into the NC [neural crest] lineage seems critical, skipping the NC induction results in a complete loss of hair-inducing activity.? The group believes that directing human ES cells to neural crest cells ?might limit the variety of mesenchymal cell types to the subset that is developmentally specified downstream from NC cells in skin (e.g. cephalic DP during development, melanocytes, cephalic bulge).? Resulting cultures become ?enriched in hair-inducing DP-like cells using relatively common mesenchymal-enriching conditions, such as differentiation in serum containing medium and selection for the adherent cell types.?

The group said adult skin-derived precursors have been found in the past to be ?highly potent in hair induction, but progressive loss? of those cells during aging ?might hamper the process of isolation? of those cells.

In 2013, a Columbia University and Durham University team reported pairing up to generatesignificant hair growth, for the first time, from adult DP cells using unique 3-D cultures. Results varied between donor cells, but those groups reported they were perfecting that approach.

It?s been known for decades that some metals, including iron, accumulate in human tissues during aging and that toxic levels of iron have been linked to neurologic diseases. Common belief has held that iron accumulation happens as a result of the aging process. But research in the nematode C. elegans in the Lithgow lab at the Buck Institute shows that iron accumulation itself may also be a significant contributor to the aging process, causing dysfunction and malfolding of proteins already implicated in the aging process. The research is online in Aging

Similar to what happens in humans and other mammals, researchers found that levels of calcium, copper, iron and manganese increased as the worms aged. But iron accumulated much more than the others, said Buck faculty Gordon Lithgow, PhD, senior scientist on the project. ?We were drawn to iron because there is all this literature that links excess iron to Alzheimer?s and Parkinson?s.?

Researchers began manipulating the nematode?s diet. ?We fed iron to four day-old worms, and within a couple of days they looked like 15 day-old worms,? said Lithgow. ?Excess iron accelerated the aging process.? Lithgow says excess iron is known to generate oxidative stress and researchers expected to see changes in the worm based on that toxicity. ?Instead, what we saw looked much more like normal aging,? said Lithgow. ?The iron was causing dysfunction and aggregation in proteins that have already been associated with the aging process. Now we?re wondering if excess iron also drives aging. ?

Researchers, led by graduate student Ida Klang, also treated normal nematodes with the FDA-approved metal chelator CaEDTA ? a drug that?s used in humans at risk for lead poisoning. The drug slowed age-related accumulation of iron and extended the healthspan and lifespan of the nematodes. Klang also gave the drug to worms genetically bred to develop specific protein aggregations implicated in human disease. The chelator was also protective in those animals.

Lithgow says the work has implications for the aging research field. ?Maintaining the proper balance of metals is key to good health throughout the lifespan, and it?s pretty obvious that this delicate balance can go off-kilter with age,? he said. ?This is a phenomena that has not been extensively studied by aging researchers and it?s an area that has potential for positive exploitation.? As far as the general public is concerned, Lithgow was quick to warn people away from taking CaEDTA and other available metal chelators as anti-aging medication. ?CaEDTA has a very blunt mechanism of action and is associated with dangerous side effects in humans and the track record for other chelators is not well established,? said Lithgow, who urged people to talk to their physicians about the use of iron supplementation, especially for postmenopausal women.

Lithgow said his lab wants to find new chelators that act more like drugs and then move those drugs into testing in mice.

Reference: Iron promotes protein insolubility and aging in C. elegans

Just three years ago, a patient at Sahlgrenska University Hospital received a blood vessel transplant grown from her own stem cells.

Professors Sumitran-Holgersson and Olausson have published a new study in EBioMedicine based on two other transplants that were performed in 2012 at Sahlgrenska University Hospital. The patients, two young children, had the same condition as in the first case they were missing the vein that goes from the gastrointestinal tract to the liver.

“Once again we used the stem cells of the patients to grow a new blood vessel that would permit the two organs to collaborate properly,” Professor Olausson says.

This time, however, Professor Sumitran-Holgersson, found a way to extract stem cells that did not necessitate taking them from the bone marrow.

“Drilling in the bone marrow is very painful,” she says. “It occurred to me that there must be a way to obtain the cells from the blood instead.”

The fact that the patients were so young fueled her passion to look for a new approach. The method involved taking 25 milliliter (approximately 2 tablespoons) of blood, the minimum quantity needed to obtain enough stem cells.

Professor Sumitran-Holgersson’s idea turned out to surpass her wildest expectations — the extraction procedure worked perfectly the very first time.

“Not only that, but the blood itself accelerated growth of the new vein,” Professor Sumitran-Holgersson says. “The entire process took only a week, as opposed to a month in the first case. The blood contains substances that naturally promote growth.”

Professors Olausson and Sumitran-Holgersson have treated three patients so far. Two of the three patients are still doing well and have veins that are functioning as they should. In the third case the child is under medical surveillance and the outcome is more uncertain.

They researchers have now reached the point that they can avoid taking painful blood marrow samples and complete the entire process in the matter of a week.

“We believe that this technological progress can lead to dissemination of the method for the benefit of additional groups of patients, such as those with varicose veins or myocardial infarction, who need new blood vessels,” Professor Holgersson says. “Our dream is to be able to grow complete organs as a way of overcoming the current shortage from donors.”

Reference:

1.Michael Olausson, Vijay Kumar Kuna, Galyna Travnikova, Henrik B?ckdahl, Pradeep B. Patil, Robert Saalman, Helena Borg, Anders Jeppsson, Suchitra Sumitran-Holgersson. In vivo application of tissue-engineered veins using autologous peripheral whole blood: A proof of concept study. EBioMedicine, 2014; DOI: 10.1016/j.ebiom.2014.09.001

Recent studies have shown that added sugars, particularly those containing fructose, are a principal driver of diabetes and pre-diabetes, even more so than other carbohydrates. Clinical experts writing in Mayo Clinic Proceedings challenge current dietary guidelines that allow up to 25% of total daily calories as added sugars, and propose drastic reductions in the amount of added sugar, and especially added fructose, people consume.

Worldwide, approximately one in ten adults has type 2 diabetes, with the number of individuals afflicted by the disease across the globe more than doubling from 153 million in 1980 to 347 million in 2008. In the United States, 29 million adults (one in eleven) have type 2 diabetes and another 86 million (more than one in three) have pre-diabetes.

“At current levels, added-sugar consumption, and added-fructose consumption in particular, are fueling a worsening epidemic of type 2 diabetes,” said lead author James J. DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke’s Mid America Heart Institute, Kansas City, MO. “Approximately 40% of U.S. adults already have some degree of insulin resistance with projections that nearly the same percentage will eventually develop frank diabetes.”

The net result of excess consumption of added fructose is derangement of both overall metabolism and global insulin resistance say the authors. Other dietary sugars not containing fructose seem to be less detrimental in these respects. Indeed, several clinical trials have shown that compared to glucose or starch, isocaloric exchange with fructose or sucrose leads to increases in fasting insulin, fasting glucose, and the insulin/glucose responses to a sucrose load. “This suggests that sucrose (in particular the fructose component) is more harmful compared to other carbohydrates,” added Dr. DiNicolantonio. Dr. DiNicolantonio and his co-authors, James H O’Keefe, MD, Saint Luke’s Mid America Heart Institute, Kansas City, MO, and Sean C. Lucan, MD, MPH, MS, a family physician at Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, examined animal experiments and human studies to come to their conclusions.

Data from recent trials suggest that replacing glucose-only starch with fructose-containing table sugar (sucrose) results in significant adverse metabolic effects. Adverse effects are broader with increasing baseline insulin resistance and more profound with greater proportions of added fructose in the diet.

The totality of the evidence is compelling to suggest that added sugar, and especially added fructose (usually in the form of high-fructose corn syrup and table sugar), are a serious and growing public health problem, according to the authors.

The 2010 Dietary Guidelines for Americans say it is acceptable for some people to consume up to 19% of calories from added sugars, and the Institute of Medicine permits up to 25% of total calories from added sugars. In contrast, the World Health Organization recommends that added sugars should make up no more than 10% of an entire day’s caloric intake, with a proposal to lower this level to 5% or less for optimal health. Such levels would be more in line with what the authors would recommend and similarly restrictive to existing American Heart Association (AHA) recommendations–to consume no more than six teaspoons (24 grams) of sugar per day for women and no more than nine teaspoons (36 grams) of sugar per day for men.

While fructose is found naturally in some whole foods like fruits and vegetables, consuming these foods poses no problem for human health. Indeed, consuming fruits and vegetables is likely protective against diabetes and broader cardiometabolic dysfunction, explained DiNicolantonio and colleagues. The authors propose that dietary guidelines should be modified to encourage individuals to replace processed foods, laden with added sugars and fructose, with whole foods like fruits and vegetables. “Most existing guidelines fall short of this mark at the potential cost of worsening rates of diabetes and related cardiovascular and other consequences,” they wrote.

The authors also think there should be incentives for industry to add less sugars, especially fructose-containing varieties, to food-and-beverage products. And they conclude that at “an individual level, limiting consumption of foods and beverages that contain added sugars, particularly added fructose, may be one of the single most effective strategies for ensuring one’s robust future health.”

Eating one avocado a day as part of a heart healthy, cholesterol-lowering moderate-fat diet can help improve bad cholesterol levels in overweight and obese individuals, according to new research published in the Journal of the American Heart Association.

Researchers evaluated the effect avocados had on traditional and novel cardiovascular risk factors by replacing saturated fatty acids from an average American diet with unsaturated fatty acids from avocados.

Forty-five healthy, overweight or obese patients between the ages of 21 and 70 were put on three different cholesterol-lowering diets. Participants consumed an average American diet (consisting of 34 percent of calories from fat, 51 percent carbohydrates, and 16 percent protein) for two weeks prior to starting one of the following cholesterol lowering diets: lower fat diet without avocado, moderate-fat diet without avocado, and moderate-fat diet with one avocado per day. The two moderate fat diets both provided 34 percent of calories as fat (17 percent of calories from monounsaturated fatty acids/MUFAs), whereas the lower fat diet provided 24 percent of calories as fat (11 percent from MUFAs). Each participant consumed each of the three test diet for five weeks. Participants were randomly sequenced through each of the three diets.

Researchers found:

?Compared to the baseline average American diet, low-density lipoprotein (LDL) — the so called ‘bad cholesterol’ — was 13.5 mg/dL lower after consuming the moderate fat diet that included an avocado. LDL was also lower on the moderate fat diet without the avocado (8.3 mg/dL lower) and the lower fat diet (7.4 mg/dL lower), though the results were not as striking as the avocado diet.

?Several additional blood measurements were also more favorable after the avocado diet versus the other two cholesterol-lowering diets as well: total cholesterol, triglycerides, small dense LDL, non-HDL cholesterol, and others.

These measurements are all considered to be cardio-metabolic risk factors in ways that are independent of the heart-healthy fatty acid effects, said Penny M. Kris-Etherton, Ph.D., R.D., senior study author and Chair of the American Heart Association’s Nutrition Committee and Distinguished Professor of Nutrition at Pennsylvania State University, in University Park, Pennsylvania.

“This was a controlled feeding study, but that is not the real-world — so it is a proof-of-concept investigation. We need to focus on getting people to eat a heart-healthy diet that includes avocados and other nutrient-rich food sources of better fats,” Kris-Etherton said.

“In the United States avocados are not a mainstream food yet, and they can be expensive, especially at certain times of the year. Also, most people do not really know how to incorporate them in their diet except for making guacamole. But guacamole is typically eaten with corn chips, which are high in calories and sodium. Avocados, however, can also be eaten with salads, vegetables, sandwiches, lean protein foods (like chicken or fish) or even whole.”

For the study researchers used Hass avocados, the ones with bumpy green skin. In addition to MUFAs, avocados also provided other bioactive components that could have contributed to the findings such as fiber, phytosterols, and other compounds.

According to researchers, many heart-healthy diets recommend replacing saturated fatty acids with MUFAs or polyunsaturated fatty acids to reduce the risk of heart disease. This is because saturated fats can increase bad cholesterol levels and raise the risk of cardiovascular disease.

The Mediterranean diet, includes fruits, vegetables, whole grains, fatty fish, and foods rich in monounsaturated fatty acids–like extra-virgin olive oil and nuts. Like avocados, some research indicates that these not only contain better fats but also certain micronutrients and bioactive components that may play an important role in reducing risk of heart disease.

Animals fed a high fat diet were limited to time restricted feeding during an eight hour period each day. The mice consumed the same number of calories as those allowed to eat all day and night yet they did not develop obesity or other health problems associated with the unrestricted mice. The time restricted feeding mice even developed improved motor coordination. The regimen also improved CREB, mTOR and AMPK anti-aging pathway functions and oscillations of the circadian clock and their target genes’ expression. These changes in catabolic and anabolic pathways altered liver metabolome, improved nutrient utilization and energy expenditure. The study demonstrated in mice that the time restricted feeding regimen is a non-pharmacological strategy against obesity and associated diseases.

Improvements were found in the time restricted feeding group in the following areas:

• Fatty acid metabolism, body weight and liver health
• Glucose metabolism and tolerance
• Overt rhythms and attenuated body weight gain
• CREB, mTOR and AMPK activities and in circadian oscillator
• Diurnal rhythms in metabolic regulators and the circadian oscillator
• Hepatic glucose metabolism
• Lipid homeostasis
• Bile acid production, adipose tissue homeostasis and inflammation alleviation

The published study can be viewed at Cell Metab. 2012 Jun 6; 15(6): 848?860

After I first learned about the massive number of people suffering from Vitamin D deficiency I went to my doctor and had a blood test called 25-hydroxyvitamin D. I expected that since I have a very healthy diet, take lots of supplements and exercise outdoors (with sunscreen) that my level would be high. It turned out that my blood showed a low level of Vitamin D. Our main source is sun exposure, yet it is a double edged sword since being exposed to the sun without sunscreen can cause skin damage, premature aging of the skin and other more serious problems. When wearing sunscreen your body can’t make much Vitamin D. I started taking 5000 IU/day of Vitamin D3 and after a few months I tested in the middle of the normal range. I have continued to take that much Vitamin D for years now and my yearly blood tests continue to be in the middle of the normal range. Everyone is different so the recommendation is to get tested and if you are low take at least 1000 IU of Vitamin D3/day or even as much as 5000 IU/day depending upon your blood test results and your doctors recommendations. Given the large amount of time that most people spend indoors combined with the use of sunscreen the RDA of 400 IU of Vitamin D is not enough for a massive number of people.

Following is a summary of the article “The Vitamin D Epidemic and its Health Consequences” that was published in The Journal of Nutrition.

“Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children?s bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one?s vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination. ”

“Vitamin D, known as the ?sunshine vitamin,? has been taken for granted and, until recently, little attention has been focused on its important role for adult bone health and for the prevention of many chronic diseases. It has been assumed that vitamin D deficiency is no longer a health issue in the United States and Europe. However, it is now recognized that everyone is at risk for vitamin D deficiency.”

The full article published in The Journal of Nutrition can be found here: https://jn.nutrition.org/content/135/11/2739S.full

In a study of more than 17,000 Canadians published in 2009 by Dr Peter Katzmarzyk and colleagues at the Pennington Biomedical Research Center they found links between time spent sitting and mortality. “Individuals who sat the most were roughly 50% more likely to die during the follow-up period than individuals who sat the least, even after controlling for age, smoking, and physical activity levels.”

Now new research suggests that taking short but frequent walks can counteract the harm caused by sitting for long periods of time.

The researchers found that even just a five-minute stroll can help.

“American adults sit for approximately eight hours a day,” study author Saurabh Thosar, now a postdoctoral researcher at Oregon Health & Science University, said in an Indiana University news release. “The impairment in endothelial function is significant after just one hour of sitting. It is interesting to see that light physical activity can help in preventing this impairment.”

According to background information from Indiana University, sitting for a prolonged period of time can cause blood to pool in the legs. This happens because muscles are not contracting and pumping blood to the heart as effectively. As a result, the ability of blood vessels to expand from increased blood flow can become impaired. Being sedentary is also linked to high cholesterol and a larger waistline, which increase the risk for heart and metabolic disease.

“There is plenty of epidemiological evidence linking sitting time to various chronic diseases and linking breaking sitting time to beneficial cardiovascular effects, but there is very little experimental evidence,” said Thosar, who was a doctoral candidate at IU’s School of Public Health-Bloomington when the study was conducted. “We have shown that prolonged sitting impairs endothelial function, which is an early marker of cardiovascular disease, and that breaking sitting time prevents the decline in that function.”

The researchers examined the effects of three hours of sitting on 11 healthy men who were not obese. The men, who ranged in age from 20 to 35 years old, participated in two trials.

First, the men sat for three hours without moving their legs. When the study began and once every hour afterwards, the function of their femoral artery was measured with a blood pressure cuff and ultrasound technology.

During the second trial, the men sat for three hours but also walked on a treadmill for five minutes after 30 minutes, 1.5 hours and 2.5 hours. The men walked at a slow pace of 2 miles per hour. The function of their femoral artery was again measured with a blood pressure cuff and ultrasound technology.

Overall, the researchers found, the ability of the arteries in the legs to expand was reduced by as much as 50 percent after just one hour of sitting. The men who walked for five minutes for each hour they spent sitting, however, had no reduction in the function of their arteries during the three-hour period.

The researchers concluded that the increased muscle activity and blood flow from the small amount of exercise offset the negative impacts of sitting.

By Mary Elizabeth Dallas in HealthDay News. The research was published Sept. 8 in the journal Medicine & Science in Sports & Exercise.

UCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.

Working with fruit flies, the life scientists activated a gene called AMPK that is a key energy sensor in cells; it gets activated when cellular energy levels are low.

Increasing the amount of AMPK in fruit flies? intestines increased their lifespans by about 30 percent to roughly eight weeks from the typical six weeks and the flies stayed healthier longer as well.

Stem Cell 100^TM and Stem Cell 100+^TM both contain several compounds that activate AMPK. They also act on a number of additional anti-aging pathways which allowed us to double fruit fly lifespan as well as greatly increase their healthspan (the length of time they were healthy and active).

The research, published in the open-source journal Cell Reports, could have important implications for delaying aging and disease in humans, said David Walker, an associate professor of integrative biology and physiology at UCLA and senior author of the research.

?We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated,? Walker said.

Walker said that the findings are important because extending the healthy life of humans would presumably require protecting many of the body?s organ systems from the ravages of aging, but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. The study suggests that activating AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain.

Humans have AMPK, but it is usually not activated at a high level, Walker said.

?The ultimate aim of our research is to promote healthy aging in people.?

The fruit fly, Drosophila melanogaster, is a good model for studying aging in humans because scientists have identified all of the fruit fly?s genes and know how to switch individual genes on and off. The biologists studied approximately 100,000 of them over the course of the study.

Lead author Matthew Ulgherait, who conducted the research in Walker?s laboratory as a doctoral student, focused on a cellular process called autophagy, which enables cells to degrade and discard old, damaged cellular components. By getting rid of that ?cellular garbage? before it damages cells, autophagy protects against aging, and AMPK has been shown previously to activate this process.

Ulgherait studied whether activating AMPK in the flies led to autophagy occurring at a greater rate than usual.

?A really interesting finding was when Matt activated AMPK in the nervous system, he saw evidence of increased levels of autophagy in not only the brain, but also in the intestine,? said Walker, a faculty member in the UCLA College. ?And vice versa: Activating AMPK in the intestine produced increased levels of autophagy in the brain and perhaps elsewhere, too.?

?Matt moved beyond correlation and established causality,? he said. ?He showed that the activation of autophagy was both necessary to see the anti-aging effects and sufficient; that he could bypass AMPK and directly target autophagy.?

In research published last year, Walker and his colleagues identified another gene, called parkin, which delayed the onset of aging and extended the healthy life span of fruit flies.

Source: UCLA