Transform Stem Cells By Turning Off One Gene

New research from the Univ. of Virginia could assist scientists in understanding how specific genes affect the bodies development. It could show how they play in diseases that are developmental and could possibly help develop new therapies.

A team was able to alter a stem cells course which made them change from turning into heart cells into brain cells just by disengaging one gene.

Previously, it has been understood that the path a cell takes upon changing into a nerve cell or a heart cell is quite rigid. But now the study shows that the process is actually quite fluid.

The method used was CRISPR genome editing to disconnect the Brm gene in the stem cells of mice that were in the process of canalization into heart cells. The result was that the cells of the mice were missing a particular protein known as Brahma. This challenged basic ideas in regards to the stem cells progression to body cells that are mature and it noted that stem cells can be looked at as a blank slate. This is the first to analyze the impact Brahma’s has on cardiac differentiation.

The scientist who made the computer model used in the study, noted the approach was unconventional. Through using the computational models, they got a better perceptive of the Brahma mechanism that can encourage changes in the fate of the cell or the process of differentiation.

There is more to be studied including what happens afterwards and what is the means that these cells turn into highly mature contractile cells? The team believes that there is a significant challenge in this field as to which implications are therapeutic. There is the need to have the ability to develop cells that are mature for transplantation into humans or to develop new drugs.

To view the original scientific study click below:
Brahma safeguards canalization of cardiac mesoderm differentiation

Gene Regulation Could be The Secret of a Longer Lifespan

A team has investigated genes that could be linked to lifespan and has found specific characteristics of certain genes. They have discovered that there are 2 regulatory systems that control gene expression. They are the pluripotency and circardian networks and are crucial to longevity. This information has important implications in the understanding of the evolution of longevity and also in offering new objectives to combat diseases that are age related.

Mammals age at significantly different rates naturally. One of these is the naked mole rat. The mole rat can live up to 41 years, which is nearly ten times longer than similar sized rodents, such as a mouse.

So what is the reason for the longer lifespan? The new research has discovered an important piece to the answer – it could be in the mechanisms that control expression of genes.

The team compared the expression of gene combinations of 26 species of mammals with different maximum lifespans. A shrew was 2 years and the naked mole rate at 41 years. They revealed genes, by the thousands, that were involved to a species’s maximum lifespan were either negatively or positively related to longevity.

They discovered that the species that were long lived usually have gene expression that was low in metabolism of energy and inflammation. The high expression of genes contributed to the repair of RNA transport, repair of DNA, and cellular skeleton organization. Earlier research had shown that attributes such as more effective repair of DNA and a less weak inflammatory response are attributes of mammals that have a long lifespan.

The short lived species had the opposite reaction with high gene expression involved in inflammation and energy metabolism and low gene expression involved in RNA transport, repair of DNA, and skeleton organization.

When the team analyzed the systems that control expression of these genes, they discovered two major systems that play a role. The negative life span gene, which are involved in inflammation and energy metabolism, are regulated by circadian networks. Their expression is confined to a specific time of day which could help control the overall gene expression in the species that were long lived. This means, some exercise can be controlled over the negative lifespan genes.

To live a longer life, we need to curb exposure to light in the evening and have healthy sleep habits, therefore inhibiting the expression of lifespan genes that can be negative.

Positive lifespan genes that are involved in RNA transport, repair of DNA and skeleton organization, are controlled by what is known as the pluripotency network. It involves reprogramming somatic cells. These are any cells that do not reproduce into embryonic cells which can more easily regenerate and rejuvenate by repackaging DNA that has become disorganized through the aging process.

They team found that the pluripotency network evolution is activated to attain longer lifespan.

The pluripotency network and its relation to positive lifespan genes is an important discovery to understand the evolution of longevity. It can show the path for new anti-aging interventions that can activate the main positive lifespan genes. The team expects that successful anti-aging interventions could add to the increase of the expression of lifespan genes that are positive and lower the expression of the lifespan genes that are negative.

To view the original scientific study click below:
Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation

Prevention of Inflammation With a Diet Rich in Polyphenols

Foods that contain polyphenols can help counter inflammation in the older population by altering the microbiota in the intestines. They also activate the production of IPA (indole 3-propionic acid), which is a metabolite that comes from the decline of tryptophan caused by bacteria in the intestines.

Polyphenols are compounds that are natural, thought to be probiotics, and are mainly found in vegetables and fruits. A variety of polyphenols in the diet are known to have anti-inflammatory and antioxidant properties. In addition they can interact with gut bacteria to produce postbiotics such as IPA which have positive and beneficial effects on health.

The evidence is increasing verifying that a consistent diet of polyphenols can add to healthy aging. This is especially true if they are also combined with a healthy diet, routine physical activity and no alcohol and tobacco.

The study indicates that gut microbiota and polyphenols interaction can activate the growth of bacteria and is able to synthesize useful metabolites like IPA. This postbiotic has antioxidant, neuroprotective properties, and being anti-inflammatory, contributes to improving intestinal wall health. This compound will help in the avoidance of a variety of diseases that are linked with aging.

In consideration of the favorable effects of IPA on the microbiota in the gut and general health, it is vital to find strategies that can be reliable to enhance the creation of this metabolite.

The team executed a varied analysis to watch the IPA levels in the serum without analyzing the gut microbiota composition. They used fecal samples from 51 participants, 65 and older, who followed a polyphenol rich diet such as bitter chocolate, green tea, and fruits such as blueberries, pomegranates and apples.

The study results indicate that a polypheonol rich diet produced a notable increase in the IPA blood levels and a reduction in levels of inflammation and changes in the microbiota bacteria.

Surprisingly, the team did not notice similar effects in the participants who had kidney disease. This can be explained from the changes in the gut microbiota composition. These participants showed decreased amounts of the IPA at the start of the study in comparison to participants with kidneys that functioned normally.

The results may be relevant clinically because the low levels of IPA have been linked with function of the kidneys rapidly declining and chronic kidney disease.

Therefore, a diet rich in polyphenols including macrobiotic foods could increase the supply of IPA from changes in the gut microbiota composition. Increased levels of a postbiotic, such as IPA in the older population, could be helpful in preventing or delaying chronic diseases that decrease quality of life.

To view the original scientific study click below:
A Polyphenol-Rich Diet Increases the Gut Microbiota Metabolite Indole 3-Propionic Acid in Older Adults with Preserved Kidney Function

Lack of Sleep Can Disrupt Activity in Cornea Stem Cells

A new study has indicated that not getting enough sleep can negatively affect corneal stem cells in both the long term and short term potentially leading to the development of eye disease and impairment of vision.

Failing to get enough sleep is a serious health issue. In the shorter term, the condition can lead to itchy, dry eyes and hyperemia of the eye. Longer term, those who suffer from lack of sleep are at a larger risk of developing eye diseases.

A significant part of good health of the eye is having a cornea that is healthy. The transparent layer of tissue which cover the eye is the cornea. It is maintained by stem cells that are constantly replacing dying cells and mending minor eye injuries. If the corneal processes of the stem cells are dysregulated, a person might develop impaired vision or eye disease.

In the study the team looked at how lack of sleep affects stem cells of the cornea. The study conducted on mice, showed that short term lack of sleep increased the multiplication rate of stem cells of the cornea. Also, there were less antioxidants in the tear film’s composition which is protective. This composition directly affects the activity of the stem cells causing the extra cell multiplication. When eye drops, which contained antioxidants were used, activity of the stem cells returned to their normal rate.

The study suggests that lack of sleep negatively affects stem cells of the cornea which might cause vision impairment on a long term basis. Additional studies are need to confirm these processes occur in human stem cells of the cornea. And other studies are needed to test the effectiveness of local antioxidant therapies in treating health issues with the cornea due to lack of sleep.

To view the original scientific study click below:
Sleep deprivation induces corneal epithelial progenitor cell over-expansion through disruption of redox homeostasis in the tear film

Youthful Function of Old Skin Cells Reprogrammed

Researchers have discovered a new approach that will rejuvenate skin cells. The approach has enabled them to reverse the cellular biological clock by about 30 years based on molecular measures. The cells that were somewhat rejuvenated indicated signs of acting more like cells that were younger in experiments that involved imitating a wound to the skin. The study, still in its early stages, might have indications for regenerative medicine, primarily if it is able to replicate in other types of cells.

The study devised a procedure to “time jump” human skin cells 30 years, which turned back the clock of aging for cells that didn’t lose their specialized function. The work has had the ability to partially restore the behavior of older cells in addition to rejuvenating the molecular measures of biological age. The study while early in exploration, could revolutionize the field of regenerative medicine.

As people age, the function of the cells in our body begin to decline and genome gather aging marks. The goal of regenerative medicine is to replace or repair cells including old ones. An important tool in regenerative biology is the body’s capability to create “induced” stem cells. This process is due to several steps with each deleting a variety of markers that make cells specialized. These cells can possibly turn into any type of cell, but researchers are not able yet to dependently recreate the circumstances that re-differentiate stem cells into all types of cells.

The newest method overcomes the issue of completely deleting the identity of cells by stopping reprogramming part way throughout the process. The team was able to find the perfect balance amid reprogramming cells, thus making them younger biologically yet still able to recapture their specialized objective.

In 2007, the first team turned normal cells which had specific functions into stem cells with specialized capability to develop into any type of cell. The whole process of reprogramming stem cells takes about 50 days utilizing 4 key molecules known as Yamanaka factors. This new method is called “maturation phase transient reprogramming” and exposes cells to the Yamanaka factors for 13 days. Afterwards, changes that are related to aging are eliminated and the cells identity is temporarily lost. The cells that have been partly reprogrammed were allowed time to grow under conditions that were normal to see if their specific function of skin cells (fibroblasts) returned. The results from the genome analysis indicated that cells had retrieved certain markers that were distinctive of skin cells. This was confirmed by observing the production of collagen in the cells that were reprogrammed.

To show the rejuvenation of the cells, the team noticed any changes in aging hallmarks. Their understanding of aging on a molelcular level has advanced over the last few years allowing techniques that scientists can measure age related biological changes in human cells. They had the ability to apply this to their experiment to see if the extent of reprogramming in their new method was achieved.

The team looked at a variety of measures of a cells age. One is the epigenetic clock which is where chemical tags will present throughout the geonome show age. Another is the transcriptome, which is all the gene characteristics which are produced by the cell. Through these measures, the cells that were reprogrammed matched the cell profiles that were 30 years younger when compared to reference data sets.

The possible applications of the method are dependent on the cells not just appearing more youthful, but also functioning like younger cells. Fibroblasts will produce collagen which is a molecule found in skin tendons, bones and ligaments and helps to provide structure for wounds and tissues that are healing. The fibroblasts that were rejuvenated were able to produce extra collagen proteins when compared to controlled cells that didn’t undergo the process of reprogramming.

Fibroblasts will also go into areas that are needing repair. Testing was done on the partially rejuvenated cells through making an artificial cut in cell layers in a dish. They discovered that the treated fibroblasts were able to move into the opening much faster than the old cells. This is an encouraging sign that some day research could create cells that are much better at wound healing.

For the future, the team may find other therapeutic possibilities. They noted that the method can also have an effect on other genes which are related to symptoms and diseases that are age related. The MAF gene plays a role in cataract developmentment, and the APBA2 gene is linked with Alzheimer’s Disease – both indicated changes towards transcription youthful levels.

The mechanism that shows the successful transient reprogramming is not fully understood at this time, and is the next puzzle piece to explore. The team speculates that main areas of the genome which was involved in shaping the identify of the cells might escape the process of reprogramming.

The results show a large step forward to their understanding of reprogramming of cells. They have shown that cells can be rejuvenated and not lose their function and that rejuvenation appears to restore some function to older cells. Observing a reverse in aging indicators in genes linked with diseases is very encouraging for the work’s future.

To view the original scientific study click below:
Multi-omic rejuvenation of human cells by maturation phase transient reprogramming

Exercise That Is Intense May Reduce Fatty Food Cravings

Recent research has offered hope for human dieters. In the study, rats were put on a diet for 30 days and were intensely exercised. The results showed that they resisted cues for normally favored pellets that were high fat. The procedure tested the level of resistance known as “incubation of craving”, which states that the longer a desired item is denied, the more difficult it can be to ignore signals for it.

While more study is necessary, the research does imply that exercise can bolster restraint when it comes to certain food types.

A very integral part of staying on a diet is brain power – being able to say “no” to something a person might be craving but wants to abstain from. Exercise may not only be physically beneficial for loss of weight, it also can mentally help to get control over cravings for foods that are not healthy.

The study included 28 rats that were put through a training. There was a lever that could be pressed to turn on a light and then made a sound before it dispensed a pellet that was high fat. Following the period of training, testing was done to observe how many times the rats would actually press the lever just to get the light and the tone cue.

The team then split the rats into 2 groups – one group was put on a regiment of high intensity running on a treadmill, the other group had no additional exercise besides their current activity. For a period of 30 days both groups were denied access to the pellets that were high fat.

After the 30 day period, the team gave the rats back access to the levers that earlier dispensed the pellets. However, this time when the rats pressed the lever, they only got the light and sound. The rats that were denied any extra exercise now pressed the levers much more than the rats that had been put through intense exercise. This shows that exercise had reduced the desire for the high fat pellets.

In studies in the future the team plans to see the effect of different levels of exercise for this type of craving. In addition, they want to see exactly what happens in the brain with exercise to curb the craving for foods that are unhealthy.

The study is novel, however it does build on work the team did that initially defined “incubation of craving”and has studied other ways to destabilize it. The team leader also credits research that shows exercise can also curb cravings for cocaine.

It is an unsettled study question as to if food can be as addictive as drugs. Not all foods see to have have an effect that is addictive. No one really binges on broccoli for example. But, people do appear to respond to cues such as fast food ads which encourage consuming foods that are high in sugar or fat. These cues might be harder to abstain from the longer they are dieting. Being able to disregard these signals may be another way exercise will improve health.

Exercise is, of course, beneficial in a number of ways. It helps with obesity, cardiac disease and diabetes. It may also help with avoidance of some of the maladaptive foods. People are always looking for a magic pill, and exercise, which is right in front of us, has all these benefits.

To view the original scientific study click below:
Acute high-intensity interval exercise attenuates incubation of craving for foods high in fat

Breathing is the Master Clock of the Sleeping Brain

Neuroscientists have discovered that breathing will coordinate neuronal activity in the brain while it is at rest or sleep.

The brain does not switch off when we are at sleep. Instead, it is saving important memories that happened during the day. For this to occur the regions of the brain syhchronize to coordinate transmission of data between them. But it is still not understood how these mechanisms work. The thought has been that the brain has correlated activity patterns in it. However, the team has shown that breathing will act as a pacemaker that enables these brain regions to synchronize between them.

The most essential and persistent body rhythm is breathing. It exerts a powerful physiological effect on the autonomous nervous system. It also modulates a broad area of cognitive functions which include attention, perception, and thought formation. But the components of its impact on the brain and these functions are mostly unknown.

The team performed in vivo electrophysiological recordings on a large scale in mice including thousands of neuron activity across the limbic system. The results were that respiration coordinates and entrains neuronal activity in all the brain regions investigated. These included the hippocampus, visual cortex, medial prefrontal, thalamus, nucleus accumbens and the amygdala. It did this by regulating the excitability of circuits in an olfaction independent way. They were able to prove the existence of a novel non-olfactory, intracerebral mechanism that accounted for the entrainment of distributed circuits by breathing. They deemed this as “respiratory corollary discharge”.

The findings identify the existence of a link between limbic and respiratory circuits that was currently unknown. This is a deviation from the traditional idea that breathing is modulated by brain activity through the nose-olfactory route.

Coordination of sleep related activity is mediated by this mechanism in brain regions which are important for memory consolidation. It also provides the means for the co-modulation of the cortico-hippocampul circuits synchronous dynamics. These results show a significant step forward to providing the foundation for new theories that will incorporate respiratory rhythm as a fundamental mechanism underlying the communication of distributed systems during consolidation of memory.

To view the original scientific study click below:
Breathing coordinates cortico-hippocampal dynamics in mice during offline states

New Discovery for Reprogramming Lost Hearing Cells in the Inner Ear

Loss of hearing due to noise, certain cancer drugs and aging cannot be reversed due to researchers not being able to reprogram cells to evolve into the inner and outer ear sensory cells. This is fundamental for hearing after they have died. However, researchers have now found a particular master gene to program ear hair cells into an inner or outer cell. This overcomes a significant hurdle that has prevented these cells from developing and hearing to be restored.

The findings are the first time that it has been shown that a cell can switch to one type or the other type. It will supply a formerly unavailable tool that will make an outer and inner hair cell.

Approximately 8.5% of adults in the U.S. between the ages of 55-64 have disabling loss of hearing. In adults aged 65-74 it increases to almost 25% and 50% in adults who are older than 75.

Right now scientists can create an artificial hair cell. However, it is not able to tell the difference between an outer or inner cell which provides crucial functions in producing hearing. The findings are a major advancement to development of those specific cells.

When hair cells that are made by the cochlea die, hearing loss and deafness occur. The cell develops in the embryo but does not reproduce. Outer hair cells contract and expand responding to pressure of sound waves and turn up sound to the inner hair cells. They carry the vibrations to the neurons to make the sound that we hear.

The scientists found the master gene switch known as TBX2 which programs the ear cells. An inner cell is created when this gene is expressed. If the gene becomes blocked, it then becomes an outer hair cell. The capability to create one of these cells requires a gene mix. The GF1 and the ATOH1 genes are required to create a cochlear hair cell from a non-hair cell. TBX2 is then able to be turned off or on to create the needed outer or inner cell.

The aim is to reprogram the supporting cells that are laced among the hair cells to provide them with basic support into outer and inner hair cells.

The team can now work on how to make a specific inner cell and outer cell and why the outer cells are more susceptible to die and cause deafness. The scientists stress that the research is experimental.

To view the original scientific study click below:
Tbx2 is a master regulator of inner versus outer hair cell differentiation

As You Age Seven Hours of Sleep Is Optimal

A new study has shown that seven hours of sleep a night is optimal for those in their mid to older ages. And, too much or too little sleep is linked with poorer mental health and cognitive performance.

Sleep is important in maintaining great psychological health and cognitive performance. It additionally helps in keeping the brain healthy through removing products that are waste. As we age we often see changes in our patterns of sleep which includes trouble staying asleep and falling asleep and also decreased quality and quantity of sleep. It is thought that these disturbances of sleep might add to psychiatric disorders and cognitive decline in the older population.

In the study the scientists looked at data from almost 500,000 adults who were aged 38 to 73 years. Participants were questioned about their sleeping habits, well being and mental health and also participated in a group of cognitive tests. Genetic data and brain imaging were available for nearly 40,000 of the participants.

Through analyzing the data, the researchers discovered that both excessive and insufficient duration of sleep were linked with impaired performance of cognitive skills such as visual attention, processing speed, skills for problem solving and memory. Seven hours of sleep each night was the optimal quantity of sleep for performance of cognitive skills and also good for mental health. Participants experienced more symptoms of worse overall well being, depression and anxiety if they revealed sleeping for shorter and longer durations.

The team says one potential reason for the link between cognitive decline and insufficient sleep might be due to the disruption of deep sleep or slow wave sleep. This type of disruption has been known to have a close link to memory consolidation and also with the build up of amyloid. This is a significant protein that misfolds, causing “tangles” in the characteristics in the brain of some dementia forms. Also, lack of sleep may hinder the ability of the brain to get rid of toxins.

The researchers additionally discovered an association between the sleep amount and differences in the structure of regions in the brain that are involved in memory and cognitive processing. And, once again it also showed more changes linked to less or greater than seven hours of sleep.

Experiencing an unvarying seven hours of sleep every night without too much duration fluctuation was additionally important to good mental health, well being and performance of cognitive skills. Earlier research has also shown that sleep patterns that are interrupted are linked with increased inflammation which indicates a susceptibility to diseases that are age related.

While the team cannot say for sure that too much or too little sleep may cause cognitive problems, their analysis looking at participants over a longer time period seems to support this thought. However, the reasons why people who are older have poorer sleep appears to be complicated, influenced by a combination of brain structure and genetic makeup.

The findings have suggested that excessive or insufficient duration of sleep might be a risk factor for decline in cognition with aging. This is supported by earlier research that has reported an association between the risk of developing dementia and Alzheimer’s Disease and duration of sleep in which decline in cognition is a hallmark symptom.

Getting a good night of sleep is important during all the stages of life, but is particularly important as people age. Finding ways that will improve sleep for the older population could be imperative to helping them keep up good well being and mental health and in addition avoiding decline in cognition skills and particularly for people with dementias and psychiatric disorders.

To view the original scientific study click below:
The brain structure and genetic mechanisms underlying the nonlinear association between sleep duration, cognition and mental health

Hallmarks of Aging Reversed with Fecal Transplants

As we search for the fountain of youth, fecal transplants might seem to be an unlikely method in the process of reversing aging. However, researchers have shown evidence from their study on mice, that fecal microbiota transplanting from young mice into older mice may reverse signs of aging in the brain, eyes, and gut.

In the study, microbes from older mice created inflammation in young recipient’s brains and reduced an important protein which is needed for correct vision. The discoveries have shown that gut microbes have a part in the regulation of some negative effects of aging and opens up the opportunity of therapies that are gut microbe based to combat the decline in older life.

The ground breaking work provided exciting realizations for the involvement of microbes in the gut in aging and the decline of brain and vision function. It also provides a possible solution from replacement therapy with gut microbes.

It is known that the microbe population that people carry in the gut, which is collectively known as gut microbiota, is associated with health. Many diseases are linked to changes in the behavior and types of viruses, fungi, bacteria and other microbes in a person’s gut.

Some changes in the composition of the microbiota occur as people age, negatively affecting immunity and metabolism. This can be directly linked to age related disorders such as cardiovascular, inflammatory bowel disease, metabolic, neurodegenerative and autoimmune disorders.

In understanding the results of the changes as we age in the microbiota, the team transferred gut microbes from older mice into young healthy mice and vice versa. Then they observed what affects it had on inflammation of aging in the brain, vision and gut which all suffer from the decline of function as a person gets older.

This study discovered that the microbiota from the older donor mice led to a loss of stability of the gut lining. This allowed bacterial products to incorporate into circulation, which caused inflammation in the eyes, brain and the immune system.

Inflammaging which is chronic age related inflammation, has been linked with activation of very specific immune cells that are in the brain. These particular cells became greatly activated in the younger mice who had received microbiome transplants that were aged.

The researchers additionally noted specific proteins in the eye linked with degeneration of the retina that were at higher levels in the younger mice who had received microbiota from the older donors.

In aged mice, these negative developments in the eye, brain and gut could be restored through transplanting gut microbiota from the younger mice.

In continuing studies, the researchers are in the process to try and understand the long term effects that were positive can last. They also hope to identify the components that are beneficial of the young mice microbiota and what the impact is on organs that are far off from the gut.

The microbiota of the younger mice, and the older mice who had been given younger transplants of microbiota, were fortified in bacteria that was beneficial and had previously been linked with good health in both humans and mice.

The team also analyzed the products that these bacteria are producing by breaking down certain elements of what we eat. This has shown major changes in certain fats (lipids) and metabolism of vitamins which could be associated to the shifts that are seen in cells that are in the brain and eyes.

The same pathways live in people and the gut microbiota of humans also will change greatly as we get older, but the team caution that extrapolating the results of their research to humans until studies that are similar in older people can be made.

A new facility for MRT (Microbiota Replacement Therapy) which is also known as FMT (Fecal Microbiota Transplantation) is being built that will enable these trials in addition to new trials for conditions that are microbiota related.

The team was excited to discover that through changing the gut microbiota of older people, they could rescue indicators of age related decline which is commonly seen in conditions that are degenerative in the eye and brain.

The results provide additional evidence of the major links between gut microbes and the healthy aging of organs and tissues of the body. They hope their findings ultimately contribute to understanding how manipulation of diet and gut bacteria can maximize better health as we age.

Fecal transplants are relatively safe and rarely spread disease as long as they are lab tested for diseases and are from very healthy donors. At one time doctors could order them for their patients, however the FDA in the US now requires extreme illness before they are allowed. This is sad since side effects and complications have been rare.

To view the original scientific study click below:
Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain

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