Physical Activity May Play a Stronger Role Than Genes In Longevity

A recent study has asked whether there are links between a person being physically active or being sedentary can be associated with a higher risk of death. The question became – does the risk change at all if a person is genetically predisposed to live a longer life? Earlier research has indicated that low physical activity and more time spent sitting are linked with a higher risk of death.

The study’s goal was to see if there is an association between sedentary time and physical activity with death varied, based on a variety of levels with a person living a longer life based on genetic predisposition.

For this research, a team in 2012, began to measure the physical activity of 5,446 women in the U.S. who were 63 years of age of older. They followed them for 8 years to determine their mortality. The women wore a research grade accelerometer for up to 7 days measuring the amount of time they were sedentary, moving and the intensity of their physical activity and sedentary time.

The ensuing study discovered that a higher level of light activity and moderate to vigorous activity were linked to the risk of death at a lower level. The findings also found that a higher sedentary time was linked with death at a higher risk. These links were consistent among women who had a variety of levels of genetic predisposition for a longer life.

The study indicated that even if a person isn’t likely to live long based on their genes, they can still extend their lifespan by participating in positive lifestyle behaviors such as sitting less and regular exercise. Conversely, even in a person’s genes predispose them to a long life, being physically active is still crucial to achieve a longer life.

With the aging population in the U.S. and longer time spend participating in lower intensity activities, the study supports recommendations for older women to participate in physical activity of any intensity to reduce their risk of disease and premature death.

To view the original scientific study click below:
Associations of Accelerometer-Measured Physical Activity and Sedentary Time With All-Cause Mortality by Genetic Predisposition for Longevity

Aging Reversed / ABC News

Now researchers have found a way not just to stop, but, reverse the aging process. The key is something called a telomere. We all have them. They are the tips or caps of your chromosomes. They are long and stable in young adults, but, as we age they become shorter, damaged and frayed. When they stop working we start aging and experience things like hearing and memory loss.

In a recent study published in the peer reviewed journal Nature scientists took mice that were prematurely aged to the equivalent of 80-year-old humans, added an enzyme and essentially turned their telomeres back on. After the treatment they were the physiological equivalent of young adults. You can see the before and after pictures in the videos above. Brain function improved, their fertility was restored it was a remarkable reversal of the aging process. In the top video the untreated mouse shows bad skin, gray hair and it is balding. The mouse with it’s telomeres switched back on has a dark coat color, the hair is restored and the coat has a nice healthy sheen to it. Even more dramatic is the change in brain size. Before treatment the aged mice had 75% of a normal size brain like a patient with severe Alzheimers. After the telomeres were reactivated the brain returned to normal size. As for humans while it is just one factor scientists say the longer the telomeres the better the chances for a more graceful aging.

The formal study Telomere dysfunction induces metabolic and mitochondrial compromise was published in Nature.

Additional information published by Harvard can be found in the following articles.

Scientists Find Root Molecular Cause of Declining Health in the Old

Decoding Immortality – Smithsonian Channel Video about the Discovery of Telomerase

While scientists are not yet able to accomplish the same results in humans we believe we have developed a nutraceutical to help prolong youth and possibly extend life until age reversal therapy for humans becomes available.

Stem Cell Secret’s of 115 Year Old Woman

New evidence that adult stem cells are critical to human aging has recently been published on a study done on a super-centenarian woman that lived to be 115 years. At death, her circulating stem cell pool had declined to just two active stem cells from stem cell counts that are typically more than a thousand in younger adults. Super-centenarians have survived all the normal diseases that kill 99.9% of us before 100 years of age, so it has been a mystery as to what actually kills these hardy individuals. This recent data suggest that stem cell decline may be the main contributor to aging. If so, stabilizing stem cells may be the best thing one can do to slow your rate of aging.

There are many theories of aging that have been proposed. For example, damage to cells and tissues from oxidative stress has been one of the most popular fundamental theories of aging for more than half a century. Yet antioxidant substances or genes that code antioxidant enzymes have proven largely ineffective in slowing aging when tested in model animals. Thus, interest by scientists has shifted to other hypotheses that might provide a better explanation for the slow declines in function with age.

Stem cells provide one such promising mechanism of aging. Of course, we all know that babies are young and vigorous, independent of the age of their parents. This is because adults have embryonic stem cells that can generate young new cells needed to form a complete young baby. Indeed, these embryonic stem cells are the product of continuously evolving stem cell populations that go back to the beginning of life on earth over 3.5 billion years ago!

In adults, the mostly immortal embryonic stem cells give rise to mortal adult stem cells in all the tissues of the body. These adult stem cells can regenerate your cells and tissues as they wear out and need replacement. Unfortunate, adult stem cells also age, which leads to fewer cells and/or loss of function in cell replacement. As functional stem cells decline, skin and organs decline with age.

Blood from world’s oldest woman suggests life limit

Time Magazine: Long-Life Secrets From The 115-Year-Old Woman

Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis

Abstract
The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.

Growing Transplantable Arteries From Stem Cells

From the early 1900’s blood banks have been crucial in medical care. A team is now wanting to take the concepts a step further by utilizing stem cells in creating new arteries for people that have cardiovascular diseases. They have discovered a drug that might help decrease complications in people who undergo bypass surgery.

There are 2 cellular building blocks of arteries that are functional, one of which is smooth muscle cells. A team was able to perfect the process of building them by using pluripotent stem cells along with a drug called RepSox. The identical compound may additionally lower the risk of a possibly dangerous complication that is frequently seen in people who undergo restorative surgeries like stents, balloon angioplasty and arterial disease bypass surgery.

The team used single cell CRISPR-Cas9 and single cell RNA sequencing to determine the pathways that can control differentiation of arterial endothelial cells, which are pillars of arteries. From manipulation of the pathways they were successful at generating arterial cells that were functional. They focused on cells that are smooth muscle.

Growth factors that have been widely used for production of smooth muscle cells from stem cells can account for an irregular thickening known as intimal hyperplasia. Initial hyperplasia can lead to blood vessel narrowing known as restenosis. It is a frequent problem in differentiation of smooth muscle cells and if you want an artery that is useful, you do not want this risk.

Restoring the contractile ability of cells that are smooth muscle and hence facilitate better flow of blood, the team utilized high throughput screening in order to find small molecules that can overcome the problem. RepSox emerged from 4,804 different drugs. In comparison to frequently used growth factors, they discovered that RepSox inhibited intimal hyperplasisa in a rat balloon model of injury and it is less expensive and more stable.

The team thinks RepSox may additionally serve as a medication to treat restenosis in people after surgery. At the present, there are 2 FDA approved medications to address the problems and they are not cell type specific leading to side effects. The team found that RepSox suppresses intimal hyperplasia with fewer side effects.

It is hard to repair the cardiac system when damages occur, therefore, scientists are looking into various regenerative methods. One team discovered a protein known as CXCL12 could grow ancillary arteries when the major arteries of the heart are blocked. It has been found that the Hippo signaling pathway, which controls the size of organs and cell death, can prevent damage to heart muscles from repairing themselves. When the team silenced it, the heart’s ability to pump in mouse models that had heart failure was restored.

From this study the team is now nearing their goal of building arteries, but there is still lots of work ahead. This cell type is an improvement from earlier efforts, but it still isn’t mature. The team needs to generate these cells to become more mature which would make them like a native artery and make it more functional.

To view the original scientific study click below:
A Human Pluripotent Stem Cell-Based Screen for Smooth Muscle Cell Differentiation and Maturation Identifies Inhibitors of Intimal Hyperplasia

Reprogramming Skin Cells Into Neurons For Brain Disorders

A new study has developed a novel method for studying age related disorders of the brain. The team has focused on the neurodegenerative disorder Huntington’s Disease for the research.

The difficulty in recreating adequate animal or cellular models of disease is an issue that has limited progress towards new treatment. For example, Huntington’s disease, which affects about 30 thousand people globally, is characterized by uncontrollable jerky movements of specific limbs. This makes it difficult to study because there are no human cell cultures available for research purposes. However, one way around these obstacles could be through reprogramming cells again rather than using traditional methods.

The study on Huntington’s disease provides an innovative process by reprogramming skin cells into neurons. This allows them for the first time ever, not just at a cellular level but also on an emotional one too. This could be important when it comes down to studying age related brain disorders such as Alzheimer’s or Parkinson’s.

Researchers were able to reprogram skin cells from patients that have Huntington’s disease converting them into neurons. They then compared the “reprogrammed” brain cell samples against people that are healthy. The findings showed several defects unique only among those suffering from HD; namely an inability to break down certain proteins that may cause energy shortage or increased trafficking rates within the body’s system leading up toward illness onset (traffic overload).

They found that these reprogrammed neurons keep their biological age, which could make them an excellent model system This means they are old and can be used as a reference in studying other neurodegenerative disorders such Alzheimer’s or Parkinson’s disease. The findings are important for future studies using this model system and may also provide insight into how aging affects our health over time.

To find a cure for Huntington’s disease, scientists need to investigate the progression of this deadly condition in living organisms. Researchers are using cells taken from patients with HD and studying them outside their bodies- something that has never been done before.

The model was created for this purpose and so far it seems accurate. More research is needed on how useful these findings really are when applied towards human treatments or even prevention strategies.

To view the original scientific study click below:
Distinct subcellular autophagy impairments in induced neurons from patients with Huntington’s disease/a>

It Isn’t All In The Genes – Are We Inheriting More Than We Think?

Scientists have made a groundbreaking discovery about the mechanisms of healthy development in embryos, which could change our understanding on what we inherit from parents and how they shape us. The new research suggests that mothers may be passing on more of their DNA than we thought, with an epigenetic legacy for future generations.

It’s a recently discovered phenomenon called “epi-genetics”. The study, led by researchers from WEHI in Melbourne, Australia has significantly broadened our understanding of which genes have information passed down through generations and what proteins control this unusual process.

We all know that our genetics determine who we are, but what if there were other factors involved? DNA contains the instructions for producing all cells in your body. It’s really hard to change yourself and pass on these new changes because they happen through alterations of chromatin structure around genes which cause them not to be read by protein-coding regions any longer – so no products get made! This means you can have different versions or “epigenes” depending how much nutrition improves during development.

And it turns out that mothers can pass on their genes through epigenetics to a tiny extent. This means we need more research into how this works and what other factors come in play when determining whether or not an individual will have certain traits based off the DNA they’ve been given at birth. The new research has shown that a mother’s supply of protein can affect the genes which drive skeletal patterning in their offspring.

The discovery that mother’s DNA contains information passed on through generations has a deep impact on how we view ourselves. With this new understanding, there are many more questions than answers about what other types of environmental factors can affect our development and future health risks.

Researchers have recently discovered a new link between the mother’s eggs and her developing baby. This study focused on one protein, SMCHD1; it was found by Professor Blewitt back in 2008! The researchers wanted to see what would happen if they decreased or increased this level within an ovo- fertilized embryo before birth via maternal transfer. They monitored how many different types of Hox genes were activated throughout development as well because these play important roles during patterning for elegant structural formation.

It has been shown that mothers pass on their epigenetic information, rather than just the blueprint of genes. This is fascinating knowledge that we can now put to use. While there are more than 20,000 genes in our genome-the average human possesses around 150 of these coding regions which carry genetic information produced by mutation or choice over time. “This is the first time that we’ve seen this type of inheritance happen in human beings,” said Dr. Benetti, “and it gives us an idea about how few genes really matter over long periods.”

Research has shown that a gene called SMCHD1, which only exists in the fertilized egg after two days of conception and is unique to humans as well as other animals, can have an impact on life-long health problems. This discovery could help women with these variants live more comfortable lives by providing them opportunities for treatment options through our drug design efforts at WEHI.

To view the original scientific study click below:
Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo

New Way to Generate Human Heart Cells from Stem Cells

A new study is trying to understand early heart disease and development in relation to the mechanisms that determine cell fate. PSCs, or human pluripotent stem cells can conceivably produce a tissue the human body needs for repair. But developing technology for this to happen for a specialized cell, for example a beating heart muscle cell, has required intricate knowledge of developmental pathways and regulatory factors.

Although there has been important technological advances, types of cells that are obtained from human PSCs are still functionally immature. For example, in a human beating heart muscle cell (cardiomyocyte), the applications are limited in disease modeling and regenerative medicine. The cells that are generated don’t fully portray those that are found in the adult heart but are instead more similar to a fetal heart that is 20-weeks old.

The team utilized mouse embryo and cardiomyocytes to look into mechanisms that determine the fate of cells by modulating the peroxisome proliferator activated receptor (PPAR) signaling pathway. It plays a vital role in the development of cardiomyocytes to repeat in culture, and the cell in the womb to maturate and to progress to its specialization.

They were able to identify a response from isoform specific maturation, where PPARdelta signaling activation had the ability to augment the structural, metabolic and contractile maturation of hPSC-CMs. This being the first incident where PPAR signaling has been decoded in such an isoform specific way.

The specificity of PPARdelta, however, not PPARalha to show such an efficient effect on cardiac maturation was unexpected. The new strategy for maturation provided an easy and robust way to generate in culture mature heart cells. These can be used for a variety of applications such as disease modeling, drug screening or therapy for cell replacement in failing hearts.

The researchers were able to identify how the protein PPARdelta played a role by inducing a metabolic receptor from glycolysis to fatty acid oxidation in a heart muscle that was lab generated. This is a vital step in the controls and maturation no matter if these cells produce energy from fatty acids or glucose.

They showed that the signaling of PPARdelta plays an important role. It has the ability to turn on gene regulatory networks which increase the organization and number of mitochondria and peroxisomes, fatty acid oxidation, myofibril lay out, the contractility and the size of heart muscle cells.

To purify hPSC-CMs they are exposed to lactate and this treatment will trigger an independent molecular reaction for maturation of heart cells. In the study, the team exhibited lactate treatment along with activation of PPARdelta that increased further oxidative metabolism which allows energy generation from both fatty acids and carbohydrates.

The team developed a publicly and comprehensive accessible gene expression dataset of transcriptomic changes in hPSC-CMs which might be valuable to scientists studying PPAR lactate selection, PPAR signaling, or screening targets for drug or research testing.

The team is interested in analyzing disorders of fatty acid oxidation. This will depend on having CMs that primarily utilize fatty acid oxidation as a source of energy. They will investigate using the mature hPSC-CMs in transplants following an infarct.

The work will expand opportunities to further research biology of the human heart through multi-disciplinary avenues that incorporate transcriptomics, developmental biology, drug testing, and contractile measurements. They are headed to understanding how to use their knowledge of human development in order to improve access to human cell types that are mature.

To view the original scientific study click below:
PPARdelta activation induces metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes

How the Intestine Repairs and Replaces Itself

It is known that the intestinal lining needs to regenerate daily to be a powerful barrier to counter pathogens while allowing nutrients to be absorbed. The responsibility for this comes from the intestine’s stem cells. They need to meet a level of constant replenishment and repair. But, for this to happen, the stem cell needs to decide if the conditions of the intestine are receptive. If the stem cell makes the wrong decision or coordinates it poorly, intestinal cancer or diseases could occur.

From new research, it has been suggested that intestinal stem cells get cues from the surrounding area to decide what to do. They can then coordinate their activity over tissue through vasculature networks in the same area.

The team discovered that lymphatic capillaries, which are fine vessels responsible for transporting immune cells and draining tissue fluids, are a signaling station that communicate to the stem cell in order to control their action. From lymphatic molecular guidance, the stem cell produces daughter cells that can either self-renew to add to the reserve of stem cells or repopulate the intestinal lining.

The discoveries help understand how primary intestinal components communication disruption may add to intestinal disorders such as inflammation of the bowel. The solution to treating various diseases will be to find out who communicates with whom in this ecosystem and how it is able to reset communication networks.

Stem cells of the intestine live in crypts that reside at the bottom of thickly packed depressions in the lining of the intestine. The stem cells can stay in the crypt through renewal, or form into cells that are differentiated into specialized cells that can migrate out of the crypt replenishing the lining of the gut. In order to discern how a stem cell can balance self renewal with differentiation, there needs to be a complete profile of crypt niches.

In order to analyze the crypt, the researchers utilized various techniques which included single cell and spatial transcriptomics, allowing the team to identify types of cells at certain locations to study their signaling molecules. Results indicated that lymphatic capillaries will assemble a personal connection to the stem cells contained in the crypt and produce a variety of proteins which are crucial for their function.

One earlier protein, REELIN, appeared to be the main candidate for negotiating communication between stem cells and lymphatics. Through manipulation of the amount of REELN in laboratory grown organoid cultures in some of the experiments and genetically suppressing it in mice in other experiments, the team found the REELIN specifically controls the regenerative behavior of the stem cells in the intestine.

The lymphatic system involvement of the stem cells function is a new concept. An earlier study by the team disclosed that lymphatics are also involved closely with skin stem cells and play a crucial role in their regeneration. This leads to the suggestion that the lymphatics could be a core feature of niches of stem cells, however, their relationship to stem cells are probably tailored to the requirements of each tissue.

To view the original scientific study click below:
Lymphatics act as a signaling hub to regulate intestinal stem cell activity

People Generate Their Own Oxidation Field Changing Air Chemistry

The indoor environment is usually more dangerous than the outdoors, with 90% of people’s time spent indoors. Chemicals from a variety of sources such as outdoor pollutants can seep into your home and cause problems for you there too! When it comes to health risks our bodies are constantly being bombarded by new chemicals – some good (like oxygen), others bad such as viruses or bacteria which want nothing better then an opportunity to live off of us. You might be surprised to learn that we are extremely harmful traveling emission sources of chemicals, including those found in our skin and breath.

The answer to why our atmosphere bothers cleaning up after us is that it’s a living thing. Atmospheric chemicals react with each other and rain to disappear. The sun UV light and water vapor in the air react with each other, forming molecules which then attach themselves (and any dirt) onto these reactive ingredients as “detergents.” These detergent-like components are mostly made when solar radiation strikes oxygen or hydrogen gas present amongst other things found on earth.

Indoor air is affected by rain and direct sunlight. UV rays are mainly filtered out through glass windows, so it’s been assumed that concentration of OH radicals in indoor environments isn’t as high compared to outdoor ones. This may be due mostly because there are no strong sources like solar radiation or wild fires burning nearby which can produce abundant quantities of ultra-violet light (which we know cause damage). It also seems likely than any ozone leaking into a building from outdoors will combine with other chemicals found inside a building.

OH radicals are a byproduct of skin oils and the ozone, which can be created indoors just due to people. It has now been discovered that humans are able to transform these reactive chemicals themselves- meaning we have even more control than previously thought over how much damage will be done or protective measures taken against it! The shape and strength of its oxidation field can be determined by things like ventilation patterns or space configuration. The research team found that even outside daytime concentrations of OHs were comparable.

The reaction of unsaturated fats and oil with ozone can be quite harmful to your skin, releasing a host of squalene degradation products. One type in particular is double-bonded gas phase chemicals that react further when exposed to the airfield generating OH radicals which have been shown as an important factor for aging signs such as wrinkles or age spots due their ability to damage DNA molecules by breaking apart hydrogen bonds between bases pairs. This study measured each individual level while also determining how much total reactivity there was so we could quantify what impact this has overall over time.

When scientists tested four different people to see how well they responded in an environment with higher indoor levels of ozone, they found that not only did all participants experience adverse effects such as headaches and difficulty breathing but even those who arrived without any pre-existing medical conditions experienced these same symptoms. The team monitored each individual’s OH value before their stay began along side assessments made at regular intervals during it.

To understand how the human activated OH field compared under a variety of conditions, results from an elaborate multiphase chemical kinetic model were connected with computational fluid dynamics models. The modeling team found that the human generated field varied under a variety of conditions, beyond those tested in lab. From their results it is clear OH radicals are abundant and present forming durable spatial gradients.

The model developed by this team has been the first of its kind that can accurately predict chemical processes happening at both molecular scales (in terms of individual molecules) as well room-sized regions. It does make sense why OH would be generated from your skin reaction when reacting with air particles; they’re essentially just small versions of you!

The team’s work has found that OH can oxidize many more spaces than ozone, which creates a myriad of products right in our immediate surroundings. These impacts on health are unknown as they have not yet been studied experimentally or clinically but could be serious due to how much time we spend near chemical signals like those present from plastics and other chemicals.

The research published today has implications for our health. Chemical emissions from a variety of furniture and materials are being tested before they can be approved to sell. It would also be wise to conduct tests in the presence of ozone because oxidation processes may generate respiratory irritants such as 4-oxopentanal or other OH radical generated oxygenated species that could have negative effects, especially on children.

To view the original scientific study click below:
The human oxidation field

Eating More Protein Will Not Enlarge Muscles Without Exercise

It has been found from reviewing 49 studies from 1800 weightlifters that increasing protein intake by double the amount increased strength by 9% and added about 1 lb of muscle growth. The participants worked out for 6 weeks and lifted weights at least twice per week.

The amount of protein used in the studies was the recommended dietary allowance (RDA), which is 0.4 grams for the average person per pound of body weight. When working out with strength training and increasing protein intake it was found that any additional gain in muscle strength levels off at 0.7 grams. The extra protein consumed presented less muscle growth with aging.

The researchers found that the type of protein consumed, whether dietary or from supplements, made no difference in the amount of muscle gained. You do need more protein when trying to increase muscle growth, but consuming more than double the RDA did not change the outcome.

To add additional muscle growth, it was found that going to the gym and performing resistance exercises is what increases muscle growth. It could be beneficial to consume up to twice the protein but any extra amounts of protein from any source did not grow larger muscles. Maximum muscle can be gained from eating protein up to 50-70 grams per day.

From 15 previous studies it was shown the supplementing protein for older weightlifters offered no benefit. You cannot just eat extra protein and expect to increase muscle. With aging, almost any person will lose muscle strength and size. But you can decrease this loss brought on by aging with performing resistance exercises on a regular basis.

When you work a muscle it breaks down. In order for it to heal and grow any combination of foods that contain protein and sugar will promote healing. Protein can be found in nuts and seeds, beans and all animal products such as dairy products, eggs, fish, poultry and meat. A variety of these foods can meet the protein needs for muscle growth.

To view the original scientific study click below:
A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults