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.

Can Lifespan Be Increased Starting in Middle or Old Age?

When we first tested Stem Cell 100 on drosophila we were very pleased that it doubled both their average (mean) and maximum lifespans. As far as we know no one had ever accomplished that before. The study was conducted with a control group that received a normal diet and the SC100 group which received the same diet with Stem Cell 100 added starting the second day after hatching.

People who take Stem Cell 100 are typically middle age or older. They did not start taking the nutraceutical supplement during childhood. So we wondered what would happen if the fruit flies started it much later in life. The study was repeated with a third group added which started Stem Cell 100 at the age of 36 days. For perspective the oldest 5% of the fruit flies in the control group typically live 45 – 50 days. In the first study the average (mean) lifespan was about 20 days for the control group and 40 days for the SC100 group. So 36 days is fairly old for a fruit fly.

The results of the study with the third group starting Stem Cell 100 much later in life were better than expected. As you can see in the graphs below the maximum lifespan of the oldest 5% averaged 120 days which was almost as old as the SC100 group that started with the supplement added to their food from the second day after hatching. This result implies that one can take Stem Cell 100 later in life and still get excellent longevity benefits! Also as we described in an earlier blog post the SC100 drosophila regardless of when they started Stem Cell 100 were still flying around, fertile and laying eggs long after the oldest of the control group had died of old age showing that they stayed youthful and healthy.

Stem Cell 100+ contains the same botanical extracts as Stem Cell 100 with additional ingredients and an improved formula that make it even more effective.

Caloric Restriction Benefits Without Eating Less Food

Luigi Cornaro

It has been known for some time that reducing caloric intake tends to lengthen lifespan and improve overall health. The history of caloric restriction goes all the way back to Luigi Cornaro a nobleman who lived during the 1400’s. At the age of 40 he was suffering from failing health so he began eating less to see if that would help. As a result he recovered his health, stayed on the limited diet, and lived to be 102 years old. Of course that was an amazing achievement back when the average lifespan was only 40 to 50 years. He even wrote several books on the subject which have been translated into English.

In modern animal studies that have been conducted on caloric restriction those that were given a lower calorie diet still received the same nutrient intake of vitamins, minerals, EFA’s, amino acids, etc., but ate food with less calories. The increase in lifespan was significant in many of the studies with the restricted animals living as much as 30% – 40% longer. The results were an increase in both average and maximum lifespan as well as better health.

While it is not possible to do a scientific test of lifespan on humans it is expected that it would have a similar effect. Of course few people would not want to go through life hungry all the time even if they knew they would live a much longer lifespan.

Is there a way to achieve the benefits of caloric restriction without eating less food? Scientists have discovered that reducing calories up regulates the SIRT1 gene. What is interesting is that resveratrol has a similar effect on SIRT1. The problem is that resveratrol has a very short half life of about 14 – 17 minutes. Because it degrades so rapidly it has limited effect on humans and animals.

Is there a better way to up regulate SIRT1? The solution is to take resveratrol analogs. They have half lives that are hours long and so can reach cells deep in the human body and continue to be active for a much longer time. So by taking resveratrol analogs it is possible that many of the benefits of caloric restriction can be achieved without limiting calories.

Stem Cell 100 and Stem Cell 100+ both contain resveratrol anaologs. That is just one example of the multi-pathway approach that was taken by Dr. Villeponteau to formulate supplements that act on many different anti-aging and regenerative mechanisms at the same time.

Sun Exposure May Increase Lifespan

Sun

A 20 year long study of nearly 30,000 women in Sweden showed that those who spent more time in the sun lived longer than those who reported less sun exposure. Those with the greatest sun exposure received an extra 7 months to 2 years of life.

Because the sun?s UV light triggers chemical reactions in the skin that lead to the production of vitamin D, it?s possible that vitamin D is responsible for the health benefits of sun exposure described in this study. And that could mean vitamin D supplements would promote longer life, even without sun exposure. However, that?s only speculation and prior studies have not been able to prove this.

The authors of this study speculate that recommendations to limit sun exposure might actually do more harm than good. As long as you avoid getting burned, they suggest that avoiding the sun could have a negative health impact similar in magnitude to smoking. That?s quite a statement!

While it is very important to avoid sunburn there are problems with some sunscreens that contain chemicals that are toxic or that become oxidized by the sun so they may do more harm than good. Wearing sunscreen hasn?t reduced skin cancer cases. In fact, melanoma rates have tripled since the 1970s.

The sun is our primary source of vitamin D, an important vitamin that strengthens our bone health, helps balance our hormones, boosts our immune system and nourishes brain function. But when we apply sunscreen, we block the sun?s rays and subsequently, the production of vitamin D in our bodies.

With these simple tips, you can protect yourself from toxic sunscreen chemicals and reap the sun?s benefits at the same time!

1. Get your sunshine during off-peak hours.

The sun can cause the most damage when it?s high in the sky: anywhere from 10am to 4pm., but that may differ slightly depending on where you live.

Stick to the sunshine early in the morning or later in the day, with one little caveat: spend 10-15 minutes in the sun during peak hours to get your daily dose of vitamin D. This is all the time you need to grab your essential amount of vitamin D.

2. Don’t wash off the vitamin D.

Vitamin D is formed on the surface of your skin when it’s exposed to UVB rays from the sun, but that vitamin D doesn’t sink in right away ? it can take up to 48 hours to absorb the majority of it. But at the end of a sunny day, most of us are in the shower scrubbing off the sunscreen, sweat and sand … and sending all that lovely vitamin D down the drain.

Try to rinse your body in the shower with just water if you can. Limit your soap usage to just your pits and your bits.

3. Eat your sunscreen.

UV radiation increases free radicals in our bodies. Boost your consumption of antioxidant-rich foods like berries, leafy greens, black beans, bell peppers, carrots, green tea, raw cacao, garlic and salmon.

There?s a reason nature offers us such a beautiful bounty of foods like berries in the summertime. Sure, they’re delicious, but they’ll also help us boost our consumption of important free radical-fighters.

4. Avoid sunburns and cover up.

Wearing sunscreen lulls us into a false sense of protection. Some people believe they can frolic through the surf for hours and be 100% shielded from the sun. This is how sunburns happen!

No one wants to end up looking like a leather handbag. Don?t spend too much time in the sun all at once, and wear lightweight clothing that’ll allow you to cover your skin and still beat the heat.

5. Buy sun block that is made from natural ingredients, oil free and based on titanium oxide and/or zinc oxide.

By using these sun protection strategies, you can get the essential sun nutrients that will ultimately benefit your health and well-being.

Reference:

Avoidance of sun exposure as a risk factor for major causes of death J Intern Med. 2016 Mar 16. doi: 10.1111/joim.12496; Lindqvist PG1, Epstein E2, Nielsen K3, Landin-Olsson M4, Ingvar C5, Olsson H6.