New Gene Therapy

Researchers have developed a new technique for gene therapy by transforming human cells into mass producers of nano sized particles which are full of genetic material. This genetic material has the potential to reverse a variety of disease processes.

Although the recent research was initially intended as proof of concept, the experimental therapy slowed down tumor growth and prolonged survival in mice who had gliomas. Gliomas’ constitute close to 80% of malignant brain tumors in humans.

The technique developed takes advantage of exosomes which are fluid filled sacs that cells release as a method to communicate with other cells. While they are gaining ground as biologically friendly carriers of therapeutic materials due to the fact that there is a lot of them and they do not prompt an immune response, the trick with gene therapy is finding a method to fit those comparatively large genetic instructions inside their very tiny bodies on a scale that would have a therapeutic effect.

The newly developed method relies on patented technology that will prompt donated human cells such as adult stem cells to spit out millions of exosomes. After these exosomes are collected and purified, they function as nanocarriers containing a drug. When they are then injected into the bloodstream, they know exactly where to find their target in the body even in the brain.

The team refers to these “gifts” that keep on giving as Mother Nature induced therapeutic nanoparticles.

Previously the team made waves when they released news of a regenerative medicine discovery called tissue nanotransfection or TNT. This technique uses a nanotechnology based chip to deliver biological cargo directly into skin. This is an action that will convert adult cells into any type of cell interest for treatment within a patient’s own body.

Through looking further into the mechanism behind the success of TNT’s, the team discovered that exosomes were the secret to delivering regenerative goods to tissue far below the surface of the skin.
This technology was adapted in the current study into a technique termed cellular nanoporation.

The team placed approximately 1 million donated cells (such as mesenchymal cells which were collected from human fat) on a nano engineered silicon wafer and then used an electrical stimulus to inject synthetic DNA into the donor cells. As a result of the DNA force feeding, the cells need to eject unwanted material as part of DNA transcribed messenger RNA and also repair holes that have been poked in the membranes.

Essentially they fix the leak to the cell membrane and dump garbage out. The garbage they throw out is the exosome. What is expelled from the cell is the drug.

The electrical stimulation had a bonus effect of a thousand fold increase of therapeutic genes in a large number of exosomes released by the cells. This is a sign that the technology is scalable to be able to produce enough nanoparticles for use in humans.

Essential to any gene therapy is knowing which genes need to be delivered to fix a medical problem. The researchers chose to test the results on glioma brain tumors. They delivered a gene known as PTEN which is a cancer suppressor gene. Mutations of PTEN that turn off the suppression role can allow cancer cells to grow unchecked.

Producing the gene is the easy part. The synthetic DNA which is force fed to donor cells is copied into a new molecule which consists of messenger RNA which contains instructions required to produce a specific protein. Every exosome bubble containing messenger RNA is transformed into a nanoparticle which is ready for transport with no blood brain barrier to be concerned about.

The advantage to this is there is no toxicity or nothing to provoke an immune response. Exosomes will go almost everywhere in the body including passing the blood brain barrier. Most drugs cannot go to the brain. They don’t want the exosomes to go the wrong place. They are programmed to not only kill cancer cells, but to know where to go to find cancer cells.

Testing in mice models showed the labeled exosomes were much more likely to travel to the brain tumors and slow their growth compared to substances used as controls. Due to the exosomes safe access to the brain, the drug delivery system has promise for applications in the future for neurological diseases.

It is the hope that one day this can be used for medical needs. The team has provided the method and if somebody knows which kind of gene combination can cure a particular disease but they need a therapy, they have it.

To view the original scientific study click here: Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation

How Many Steps Per Day For a Longer Life?

For years 10,000 steps per day has been the target for many people! But there is actually nothing magical about it! The original basis for establishing that number was never based on scientific basis. In fact it was part of a marketing campaign launched in Japan in1965 to help promote a pedometer. And it is a big number that many people find hard to reach!

Dr. I-Min Lee at Brigham and Women’s Hospital along with a professor at Harvard Medical School and a researcher on physical activity, set out to discover the basis for 10,000 steps and also study its validity. Their study published in JAMA Internal Medicine set out to answer 2 questions about mortality…how many steps per day are associated with lowering the mortality rate and does stepping up the intensity level make a difference with the same number of steps?

A study was designed that included about 17,000 older women with the average age of 72. This group tends to be less active and health issues occur and become more important as people age. Between 2011 and 2015, the participants wore tracking devices during waking hours to track their steps as they went about their daily activities.

Key findings showed that sedentary women averaged 2,700 step per day. The women who averaged 4,400 steps per day had a 41% reduction in mortality. Mortality rates continued to improve progressively before leveling off at bout 7,500 steps per day. About nine fewer deaths occurred per 1,000 person years among the most active group compared to the least active group.

The research shows that if mortality is a person’s major concern, then the study suggests that you can reap benefits from 7,500 steps per day. That is 25% fewer steps than the common goal of 10,000 steps. The study indicates that even light walking can result in benefits for older women.

The study was designed to look at just two factors. Since it was about mortality, it did not relate steps per day to anything related to cognitive functions, quality of life, or physical conditions. It does not tell us how many steps are needed in order to maximize those things. And in answer to the researchers second question, they did not find that the intensity of the steps mattered.

To view the original scientific study click below:

Association of Step Volume and Intensity With All-Cause Mortality in Older Women

New Bone Healing Mechanism

Researchers at Baylor College of Medicine have revealed a new mechanism that will contribute to adult bone maintenance and repair. This new development opens up the possibility for developing new therapeutic strategies for the improvement of bone healing.

Bone repair in adults relies on the activation of bone stem cells. These cells remain poorly characterized. Periosteal stem cells have been the least understood. They comprise heterogeneous population of cells which can contribute to bone shaping, thickness and fracture repair. However, scientists have not been able to distinguish between the different subtypes of bone stem cells so they can study how the different functions are regulated.

In the new study, the researchers have developed a method which identifies different sub populations of periosteal stem cells, defines their particular function to repair fractures in bones in live mouse models, and also identifies specific factors that regular their migration and proliferation under physiological situations.

The team discovered specific markers in mouse models for periosteal stem cells. These markers identified a distinct subset of stem cells which contribute to life long bone regeneration in adults. They also discovered periosteal stem cells will respond to mechanical injury through engaging in healing of the bone. They are vital to bone fracture healing in adult mice and their contribution to regeneration of the bone is higher than the stem cells in the bone marrow.

They also discovered periosteal stem cells respond to inflammatory molecules known as chemokines. These molecules are typically produced during injury of bone. They respond to chemokine CCL5.

Periosteal stem cells contain receptors, molecules on their cell surface, that will bind to CCL5. This sends a signal to the cells telling them to migrate toward the injured bone and begin repairing it. By deleting the CCL5 gene in mice, marked defects in bone repair occurred and delayed the healing process. When CCL5 was supplied t the CCL5 deficient mice, bone healing accelerated.

The team’s findings suggest possible therapeutic applications. For example, in people who suffer from osteoporosis or diabetes in which bone healing can be slow and can lead to a variety of complications which can result in limited mobility, accelerated bone healing could reduce hospital stays and improve their prognosis.

The findings contribute to a much better understanding of the mechanisms behind bone healing. This is one of the first studies to indicate that bone stem cells are heterogeneous and that a variety of subtypes have unique properties which are regulated by specific mechanisms. The team has identified markers which enabled them to identify the bone stem cell subtypes and have identified what each subtype contributes to the health of bone.

To view the original scientific study click below

Identification of Functionally Distinct Mx1 SMA Periosteal Skeletal Stem Cells

Stress Speeds Up Chromosone Aging

New research has provided the first evidence that along with pollution, smoking, obesity, and diesel exhaust, oxidative stress acts directly on telomeres to speed up cellular aging. The research has shown how stress can cause our biochemical body clock built into our chromosomes to tick faster.

DNA which is the genetic material found in our cells, doesn’t freely float in cell nuclei, but is organized into clumps of chromosomes. When a cell divides and produces a replica of itself, it has to make a DNA copy of itself. During this process a tiny portion is always lost at one end of the DNA molecule.

To protect some of the vital portions of DNA from being lost in this process, the ends of the chromosomes are capped with telomeres. These telomeres are gradually shortened during cell division. Gradual shortening of the telomeres acts like a cellular clock. Each replication causes them to get shorter and they eventually reach a point when they become too short sending the cell into a programmed death process.

Cellular aging is just one of the components related to aging. But it is one of the most important. The gradual deterioration of tissues in our body and the irreversible death of cells are responsible for some of the most visible effects of aging. This includes wrinkles, physical fitness and neurodegenerative diseases.

So far answers to what are some of the factors that may slow down or speed up the loss of our telomere clock have so far been inconclusive. Some studies have shown glimpses of potential mechanisms which suggest things like infections and even dedicating extra energy to reproduction may could possibly accelerate shortening of the telomeres and thus speed up cellular aging.

Although the evidence so far is piecemeal, these factors all seem to have one thing in common. They all cause physiological stress. Our cells become stressed when their biochemical processes are disrupted either by a lack of resources or for some other reason. If cells lose too much water they become subject to dehydration stress.

Other types of stress also count. Overwork and tiredness can put us under chronic stress. Anxiety for prolonged periods, emotional stress, and lack of sleep can also alter internal cellular pathways which includes telomere functioning. The question then becomes, can a variety of stress factors experienced by a person actually accelerate their rate of aging?

Many studies have looked at this question in specific species such as rats, mice, and various bird and fish species, both in the wild and in the lab. Findings from these studies suggest that telomere loss is profoundly affected by stress. The type of stress is important with the strongest negative effects caused by competition for resources, pathogen infections, and investment of energy into reproduction. Other kinds of stress such as a poor diet and human disturbance or urban living, also hastened cellular aging although to a lesser extent.

Oxidative stress was identified as a possible factor as to why stress can exert such a powerful influence on our cellular clocks. When cells are exposed to stress, it often manifests itself through an accumulation of oxidizing molecules such as free radicals. Free radicals are chemically reactive molecules that can attack the protective telomere end caps. These end caps which are exposed ends of our chromosomes are perfect targets for these chemically reactive molecules.

Analysis does suggest that no matter the type of stress experienced, this oxidative stress just might be the actual biochemical process that links stress to telomere loss.

Additional research is needed to determine if the results mean that we should consume more antioxidants to help combat oxidative stress and therefore guard our telomeres. The researchers note that this is not the secret to stop the aging process. It is too fundamental to biology to simply get rid of completely. It does however highlight that reducing stress can have great beneficial benefits on our bodies. By ensuring we are drinking enough water, getting enough sleep, maintaining a healthy balanced diet, and engaging in physical activity, it will help keep our cells functioning nicely.

To view the original scientific study click below:

The association between stressors and telomeres in non-human vertebrates: a meta analysis.

Low Fat Milk Linked to Less Aging in Adults

A study conducted at Brigham Young University by exercise scientists has found that people who consume low fat milk experience several years less biological aging when compared to those who drink high fat milk, both 2% and whole milk. This supports existing dietary guidelines which do not recommend high fat milk as part of a healthy diet.

The study assessed 5,834 adults and included data from the National Health and Nutrition Examination Survey as well as questionnaires for the participants. They looked at the relationship between telomere length along with milk intake frequency (daily drinkers vs. weekly drinkers or less) and the milk fat content that was consumed (whole vs. 2% vs. 1% vs. skim).

Telomeres are the end caps of human chromosomes and act like biological clocks. They are correlated with age. As people get older, their telomeres get shorter. People who consumed more high fat milk showed telomeres that were significantly shorter.

For every 1% increase in milk fat consumed (drinking 2% vs. 1% milk), telomeres were 69 base pairs shorter in the adults in the study. This translates into more than four years in biological aging. In the very extreme milk drinkers, the adults who drank whole milk had telomeres that were a striking 145 base pairs shorter.

Half of the adult participants in the study consumed milk on a daily basis with another quarter consuming milk at least weekly. Less than a third of the adults consumed full fat milk and an additional 30% reported drinking 2% milk. Approximately 10% consumed 1% milk and another 17% consumed non fat milk. 13% did not drink any cow milk.

Surprisingly, the study found that people who did not consume milk at all had shorter telomeres than adults who drank low fat milk meaning they aged quicker than skimmed milk drinkers. This suggests that there may be some anti aging benefits to consuming milk, but there is sweet spot to be found.

The study suggests that the milk fat and subsequent link with cellular aging was most likely due at least in part to increases inflammation and oxidative stress caused by the increase in saturated fat consumption. The team believes that this saturated fat in high fat milk is the culprit that causes the damage and contributes to the death of tissues in the human body.

Milk is one of the most controversial foods in the U. S. Current dietary guidelines for Americans encourage adults to consume low fat milk, both 1% and non-fat, and avoid high fat milk altogether. It isn’t necessarily a bad thing to drink milk, but according to the study, the type of milk matters.

To view the original scientific study click below

Milk Fat Intake and Telomere Length in U.S. Women and Men: The Role of the Milk Fat Fraction

New Discovery May Extend Healthy Lifespan by 50%

Scientists have identified pathways that could enable humans to live for well over 100 healthy years according to one of the scientists who participated in the research. The synergistic cellular pathways for longevity that increase the lifespan five fold were discovered in C. elegans which are a nematode worm used as models in aging research. This translates to extending human lifespan by about 50%.

C. elegans are popular models for aging research because they share many of its genes with humans and due to its short lifespan of three to four weeks, scientists can quickly assess the effects of genetic and environmental interventions for extending healthy lifespan.

The discovery of two major pathways governing aging in C. elegans has created intensive research. These pathways are conserved which means they have been passed down to humans through the evolutionary process. A variety of drugs that can extend healthy lifespan through altering these pathways are currently under development. The discovery of the synergistic effect has opened the door to more effective therapies aimed at anti aging.

The recent research used a double mutant in which the insulin signaling IIS and TOR pathways were genetically altered. Because an alteration of the IIS pathways will yield a 100% increase in lifespan and an alteration of the TOR pathway yields a 30% increase, the double mutant would be expected to live 130% longer. However, its lifespan was amplified by 500%.

Despite this discovery in C. elegans of cellular pathways that govern aging, it wasn’t clear how these pathways interact with each other. Through helping to characterize these interactions, the research team is paving the way for needed therapies to increase healthy lifespan for the rapidly aging population.

The synergistic extension is something the team calls “wild”. The effect wasn’t one plus one equals two. It was one plus one equals five. The findings demonstrate that nothing throughout nature exists in a vacuum. To develop the most effective treatments for anti aging, longevity networks rather than individual pathways needs to be looked at.

This discovery of the synergistic interaction might lead to the use of combination therapies with each affecting a different pathway to extending human healthy lifespan. The synergistic interaction might also explain why researchers have not be able to identify a single gene that is responsible for the ability of some humans to live to very old ages free of major diseases.

To view the original scientific study click below

Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity.

High Levels of Exercise and Slower Cellular Aging

New research has revealed how a high level of exercise can slow one type of aging. This is the kind of aging that occurs within our cells. We just have to be willing to put in some sweat equity!

Researchers at Brigham Young University have found that people who consistently perform physical activity at a high level have significantly longer telomeres when compared to those have live a sedentary lifestyle as well as those who are moderately active.

Telomeres are protein end caps on our chromosomes. The are like our biological clock and are strongly tied to aging. Every time a cell replicates, it loses a tiny bit of the end caps. As a result, the process of aging gradually shrinks or shortens our telomeres.

The team analyzed data from 5,823 adults who participated in the CDC’s National Health and Nutrition Examination Survey. This survey is one of the few indexes that includes telomere length values for the study participants. The index also includes data for 62 activities participants may have participated in over a 30 day period. This data was analyzed to calculate the participant’s levels of physical activity.

The research found that adults with high physical activity levels have telomeres with a biological aging boost of nine years when compared to those who live comparably idle lifestyles. They also have a 7 year advantage compared to those who engage in moderate levels of physical activity.

In order to be considered to be a highly active person, men must engage in 40 minutes of jogging 5 days per week and women must engage in 30 minutes of jogging 5 days per week. To see a significant difference in slowing biological aging, a little exercise won’t make it. People have to work out regularly and at high levels.

The study showed that the shortest telomeres came from people who were considered sedentary. They had 140 base pairs of DNA less at the endpoints of their telomeres compared to the highly active participants. Surprisingly, the study showed that there was no significant or meaningful difference in telomere length between the participants who were sedentary and those who engaged in low or moderate physical activity.

The exact mechanism responsible for how exercise preserves the telomeres is unknown. The team believes the mechanism may be tied to the combination of oxidative stress and inflammation. Earlier studies have determined telomere length is closely tied to those two factors. And it is well known that physical activity can suppress both these factors over time.

It is well known that regular physical activity can help reduce mortality and prolong life. Now it is known that part of that advantage might be related to the preservation of telomeres that occurs with high physical activity.

To view the original scientific study click below

Physical activity and telomere length in U.S. men and women: An NHANES investigation.

New Research into Tendon Stem Cells for Recovery

Due to the buildup of scar tissue from a variety of tendon injuries such as jumper’s knee and rotator cuffs, secondary tendon ruptures along with painful and challenging recoveries can occur. New research has shown that the existence of stem cells in tendons can potentially be harnessed to not only improve the healing of tendons but also even avoid surgery.

Tendons are the connective tissue that tethers our muscles to our bones. These tendons improve not only our stability but also facilitate the transfer of force which allows us to move. However, they are particularly susceptible to damage and injury.

Once tendons are injured they rarely fully recover. This can result in mobility limitations and often times requires long term pain management and even surgery. The problem is the fibrous scars which disrupt the tissue structure of the tendons.

The research which was conducted at the Carnegie Institution for Science, revealed all of the cell types which are found to be present in the Patellar Tendon which is found below the kneecap. This included previously undefined tendon stem cells.

Because injuries to the tendons rarely heal completely, it has been thought that tendon stem cells did not even exist. Many researchers have searched for them but to no avail until the recent work which defined them for the first time.

Stem cells are blank cells which are associated with nearly even tissue type which have not fully differentiated into a specific function. They can self renew which creates a pool from which newly differentiated types of cells can form to support a particular tissue’s function. Muscle stem cells for example differentiate into muscle cells.

The research team showed that both tendon stem cells and fibrous scar tissue cells originate in the identical space which is the protection cells that surround our tendons. Additionally, the tendon stem cells are part of a competitive system with precursors of fibrous scars. This explains why healing of injured tendons is so challenging.

The researchers demonstrated that both scar tissue precursor cells and tendon stem cells are stimulated into action by a protein known as platelet derived growth factor A. When tendon stem cells become altered so they do not respond to this particular growth factor, then only scar tissue and no new tendon cells form following an injury.

Tendon stem cells must outcompete scar tissue precursors so they can prevent the formation of difficult fibrous scars. Discovering a therapeutic way to block these scar forming cells and instead enhance the tendon stem cells could be a huge game changer for treating tendon injuries.

To view the original scientific study click below

A Tppp3+Pdgfra+ tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis.

Does Elderberry Really Minimize Flu Symptoms?

A new study by researchers at the University of Sydney’s Faculty of Engineering and IT have found that compounds contained in elderberries can directly inhibit the flu virus’s entry and also replication in human cells. These compounds can additionally help strengthen the immune response to this virus. While modern scientists have struggled to explain the medicinal benefits of herbal products and folk medicine, these methods have been used for millennia to help combat a variety of ailments.

Although the flu fighting properties of the elderberry fruit have been previously observed, the team sought to perform a more comprehensive examination of the mechanisms through which phytochemicals found in elderberries can help combat the flu virus.

The study involved the use of commercially farmed elderberries which were made into a juice serum. This serum was applied to cells at all stages after they had been infected with the flu virus…before, during and after. The phytochemicals from the juice were shown to be effective at stopping the flu virus infecting the cells.

And surprisingly to the research team, they were even more effective at inhibiting viral propagation at the later stages of the flu cycle when the cells had been infected with the virus. The study showed that this common fruit has a direct and potent antiviral effect against the flu. It inhibits the initial sages of the infection by blocking key viral proteins that are responsible for viral attachment and entry into host cells.

In addition, the team identified that the solution from the elderberry also stimulated the cells to release certain cytokines. These are chemical messengers which the immune system uses for communication between different cells types in an effort to coordinate a better response against invading pathogens.

They also found that the antiviral activity of the elderberry can be attributed to its anthocyanidin compounds. These are phytonutrients which are responsible for the vivid purple coloring of the fruit.

The elderberry which is also known as sambucus nigra, is an antioxidant rich fruit most common to North America and Europe. It is commonly consumed as wine or jam. For the medicinal benefits, elderberry extract is available in table or syrup form.

The flu virus is one of the leading cause of worldwide mortality. It affects almost 10% of the world’s population and contributes to one million deaths on an annual basis.

To view the original scientific study click here: Anti-influenza activity of elderberry.

Can Intermittent Fasting Help you Live Longer?

Typically for many people a New Year is the perfect time to adopt new habits both in the gym and at the grocery store. People can be eager to try out new diets, but does scientific evidence actually support claims made for these diets?

Mark Mattson, Ph. D., a neuroscientist at John Hopkins Medicine, has studied intermittent fasting for 25 years and adopted it himself about 20 years ago. He concludes that intermittent fasting does live up to the claims that it can be a part of a healthy lifestyle.

Generally, intermittent fasting diets fall into two categories: 5:2 intermittent fasting in which people will limit themselves to one moderate sized meal two days each week, and daily time restricted eating which narrows eating times to 6 to 8 hours per day.

A variety of animal and human studies have shown that alternating between eating and fasting supports cellular health. The thought is that most likely this happens by triggering an age old adaptation to periods of food scarcity referred to as metabolic switching. This switch occurs when cells use up stores of rapidly accessible sugar based fuel and begin converting fat into energy which occurs in a slower metabolic process.

Studies have shown that this metabolic switch improves the regulation of blood sugar, suppresses inflammation, and increases the resistance to stress. Most Americans consume three meals in addition to snacks every day so they do not experience the switch and the suggested benefits.

Mattson also notes that four different studies in both people and animals found intermittent fasting also decreases blood pressure, resting heart rates, and blood lipid levels. There is also mounting evidence that this type of fasting can modify risk factors which that are associated with diabetes and obesity.

Two studies conducted at the University Hospital of South Manchester NHS Foundation Trust which involved 100 overweight women showed that the women on the 5:2 intermittent fasting diet lost the same amount of weight as women who restricted their calories. Additionally they did better with insulin sensitivity and reduced belly fat when compared to those in the reduced calorie group.

Recently, Mattson says preliminary studies have suggested that intermittent fasting could also benefit brain health. A multi center clinical trial at the University of Toronto found that 220 healthy and non obese adults who maintained a calorie restricted diet for a period of two years showed evidence of improved memory in a variety of cognitive tests. If further studies show the proof that fasting can improve learning and memory, interventions may be developed that can stave off dementia and neurodegeneration.

Mattson believes we are at a point where medical school curricula alongside advice and healthy diets and exercise may be developed. Although he recognizes that researchers do not completely understand the specific mechanisms of metabolic switching and that there are some people who or unwilling or unable to adhere to a fasting program.

With guidance and patience, most people are able to incorporate fasting regimes into their lives. It does take the body some time to adjust to intermittent fasting and to get past some of the initial hunger pangs and irritability that can accompany it. These symptoms typically pass after two weeks to a month as the brain and body become accustomed to this new habit.

To manage that hurdle, Mattson suggests that health care professionals advise patients to gradually increase the frequency and duration of the fasting periods over the course of several months, instead of going cold turkey.

To view the original scientific study click below

Effects of Intermittent Fasting on Health, Aging, and Disease.