Exercise Causes Epigenetic Changes to Your Cells

Exercise, even in small doses, changes the expression of our innate DNA. New research from Lund University in Sweden has described for the first time what happens on an epigenetic level in fat cells when we undertake physical activity.

“Our study shows the positive effects of exercise, because the epigenetic pattern of genes that affect fat storage in the body changes,” says Charlotte Ling, Associate Professor at Lund University Diabetes Centre.

The cells of the body contain DNA, which contains genes. We inherit our genes and they cannot be changed. The genes, however, have ‘methyl groups’ attached which affect what is known as ‘gene expression’ — whether the genes are activated or deactivated. The methyl groups can be influenced in various ways, through exercise, diet and lifestyle, in a process known as ‘DNA methylation’. This is epigenetics, a relatively new research field that in recent years has attracted more and more attention.

In the study, the researchers investigated what happened to the methyl groups in the fat cells of 23 slightly overweight, healthy men aged around 35 who had not previously engaged in any physical activity, when they regularly attended spinning and aerobics classes over a six-month period.

“They were supposed to attend three sessions a week, but they went on average 1.8 times,” says Tina R?nn, Associate Researcher at Lund University.

Using technology that analyses 480 000 positions throughout the genome, they could see that epigenetic changes had taken place in 7,000 genes (an individual has 20-25 000 genes). They then went on to look specifically at the methylation in genes linked to type 2 diabetes and obesity.

“We found changes in those genes too, which suggests that altered DNA methylation as a result of physical activity could be one of the mechanisms of how these genes affect the risk of disease,” says Tina R?nn, adding that this has never before been studied in fat cells and that they now have a map of the DNA methylome in fat.

In the laboratory, the researchers were able to confirm the findings in vitro (studying cell cultures in test tubes) by deactivating certain genes and thus reducing their expression. This resulted in changes in fat storage in fat cells.

Adult Stem Cells to Grow New Bone

Preparations are underway for the first known human trial to use stem cells collected from adults to grow new bone.

The cells technology, called VSEL stem cells, or very small embryonic-like stem cells, are derived from adults — not fetuses. This eliminates ethical arguments and potential side effects associated with using actual embryonic stem cells derived from a fetus, say researchers at the University of Michigan School of Dentistry and New York-based NeoStem Inc.

The research partners hypothesize that the VSEL stem cells, which mimic properties of embryonic stem cells, can provide a minimally invasive way to speed painful bone regeneration for dental patients and others with bone trauma.

U-M’s role in the study involves design, patient care and data analysis, while NeoStem provides the cells and patented technology to purify the special stem cells. Study leaders include Russell Taichman, U-M professor of dentistry; Laurie McCauley, professor and newly named dean of the U-M Dental School; and Denis Rodgerson, director of grants and academic liaisons for NeoStem. U-M’s work will take place at the Michigan Center for Oral Health Research and the U-M Health System.

“Within a year, researchers hope to begin recruiting roughly 50 patients who need a tooth extraction and a dental implant,” Taichman said.

Before extracting the tooth, U-M researchers harvest the patient’s cells, and then NeoStem’s VSEL technology is used to purify and isolate those VSEL stem cells from the patient’s other cells.

This allows U-M researchers to implant pure populations of the VSEL stem cells back into test patients. Control patients receive their own cells, not the VSELs. After the new bone grows, researchers remove a small portion of it to analyze, and replace it with an implant.

“We’re taking advantage of the time between extraction and implant to see if these cells will expedite healing time and produce better quality bone,” Taichman said. “They are natural cells that are already in your body, but NeoStem’s technology concentrates them so that we can place a higher quantity of them onto the wound site.”

U-M has applied for initial patent protection to use the VSEL stem cells to grow bone. Robin Smith, chairman and CEO of NeoStem, emphasized the importance of this study for the development of embryonic-like stem cells from the patient’s own body to treat a wide range of diseases.

World’s Oldest Person Reveals Longevity Secret

The world?s oldest living person reached another milestone Sunday when she celebrated her Sweet 116. When asked for her secret to living such a long life she said ?I mind my own business and I don?t eat junk food.?

Besse Cooper has become only the 8th person in the world and the 4th American verified to have turned that age, according to Guinness World Records.

Cooper, whose maiden name was Brown, was born on Aug. 26, 1896, in northern Tennessee the same year as comedian George Burns and writer F. Scott Fitzgerald.

In 1917 during World War I, she moved to Georgia to work as a schoolteacher. She later married Luther Cooper, and they raised four children together. He died in 1963 at age 68, according to The Walton Tribune.

The newspaper reported last year that the supercentenarian is also a grandmother of 12, great-grandmother of 15 and great-great-grandmother of one.

Walton County officials held a ribbon cutting Friday to name a bridge in honor of Cooper, who resides in a nursing home and was unable to attend the ceremony.

?The older she has gotten the more wittier she has gotten,? Cooper?s third child, Sidney, reportedly said, adding that she had a message for the bridge-naming ceremony: ?I?m glad I gave them a reason to name it.?

Although Guinness World Records first called her the world?s oldest living person in January 2011, she lost the title when it was discovered Maria Gomes Valentin, of Brazil, was born 48 days earlier.

Valentin died on June 21, 2011, just shy of her 115th birthday, and Cooper was again crowned the world?s super senior.

Cooper could still surpass another Tennessean, Elizabeth Bolden, who was 116 years and 118 days when she died in 2006.

The person with the longest human lifespan ever recorded was Jeanne Calment, of France, who was born in 1875 and died in 1997 at the age of 122.

Georgia Man’s Foot Regrown After Being Decimated by Flesh-Eating Bacteria

Once they stripped away the infected flesh, the next step was to cut off the remaining foot bone. But Osiris (USA’s leading Repair Stem Cell company) donated its products to see if it could fix the largest problem ever proposed for stem cells anywhere!

Dalton, Georgia May 2012: By the time Dr. Spencer Misner had carved away the dead and diseased flesh from Bobby Rice?s right foot last year, little remained other than bones and tendons.

?I couldn?t believe it. It didn?t look real. It looked like something out of a movie,? recalled Rice.

Today, the ankle has almost completely healed. It looks like Rice had simply scraped it. And Rice?s foot has largely healed, too. Misner credits cutting-edge stem cell treatments for saving Rice?s foot and leg.

Rice, who has diabetes, stepped on a piece of glass last fall and his foot quickly became infected. After trying a home remedy, Rice eventually went to Hamilton Medical Center in Dalton, GA, where doctors found he had a rapidly spreading necrotizing fasciitis, or in layman?s terms, flesh-eating bacteria.

Physicians treated the infection with antibiotics. However, Rice had one toe amputated. Doctors had to strip away much of the flesh from Rice?s foot and a great deal of flesh along his ankle.

?We did what we had to do,? Misner said. ?We got the infection out. We saved his life. But what do you do next? We?d normally say all you can do now is cut of his leg so he can get on with his life.?

But Misner had another idea. He contacted Ed Fickey, a sales representative for Osiris Therapeutics and asked about using the company?s new stem cell technologies to rebuild the foot and ankle.

Stem cells can grow and differentiate into many different types of cells. Stem cell treatments introduce these cells into damaged or diseased organs to repair them.

?The problem is that Bobby is an indigent patient and didn?t have the financial resources. Ed spoke to the company, and they agreed to donate the products for free,? Misner said.

Osiris provided two products called Grafix and Ovation. Fickey said they are made from adult stem cells derived from donated placenta and do not come from embryos.

?They hadn?t had a case of this magnitude before,? Misner said. ?Stem cells are starting to be used pretty extensively. They are used on burn patients to regenerate skin. But this involves muscle, bone, tendon, fat, skin, so many types of tissues.?

Misner said he asked the company for some guidelines.

?They basically said, ?You let is know what the guidelines are because we don?t have a record of anything like this being done before.? I did a literature search, and I couldn?t find anything like this before,? Misner said. ?They did connect me with a doctor in Washington, D.C. who has used stem cells quite a bit. But when I sent him the pictures (of Rice?s foot and ankle), he basically said ?Good luck.? He helped me with some general guidelines, but there was no recipe to follow.?

Misner started the treatments in November 2011, and Fickey recalls just how tricky it was.

?He (Misner) had a syringe, and he was looking for some tissue to push it into. But there was nothing but bone there,? he said. ?Now, there?s a whole fleshy foot.?

Misner has applied the stem cell treatments nine times now, and he describes the foot as more than 90 percent healed. He had to perform the first treatments in an operating room at Hamilton Medical Center because of how complicated they were. But he has been able to do the last few treatments in his office. He expects to have to do at least three more before the foot has completely regenerated.

Fickey said Osiris has been watching ?the Dalton foot? very closely.

?Each time we do an application, I send the latest pictures back, and they have always been very impressed. They wanted to see if there has been muscle growth and the answer has been yes. They wanted to see if there has been vascularization, blood flow, and there has been,? Fickey said. ?The most impressive thing is that Bobby has feeling back. We were here a couple of weeks ago and the nurse tickled his foot and he kind of jumped. We didn?t expect that. Now, we are starting to have some other cases around and we can tell them ?This is what we want to see.??

Rice said he never dreamed he would regain his foot.

?I know what it looked like. I expected he would just have to take it off. To see where it is today is just amazing,? he said.

Hearing Loss Regenerated in Damaged Mammal Ear

Hearing loss is a significant public health problem affecting almost 50 million people in the United States alone. Sensorineural hearing loss is the most common form and is caused by the loss of sensory hair cells in the cochlea. Hair cell loss results from a variety of factors including noise exposure, aging, toxins, infections, and certain antibiotics and anti-cancer drugs. Although hearing aids and cochlear implants can ameliorate the symptoms somewhat, there are no known treatments to restore hearing, because auditory hair cells in mammals, unlike those in birds or fish, do not regenerate once lost. Auditory hair cell replacement holds great promise as a treatment that could restore hearing after loss of hair cells.

In the Jan. 10 issue of Neuron, Massachusetts Eye and Ear and Harvard Medical School researchers demonstrate for the first time that hair cells can be regenerated in an adult mammalian ear by using a drug to stimulate resident cells to become new hair cells, resulting in partial recovery of hearing in mouse ears damaged by noise trauma. This finding holds great potential for future therapeutic application that may someday reverse deafness in humans.

“Hair cells are the primary receptor cells for sound and are responsible for the sense of hearing,” explains senior author, Dr. Albert Edge, of Harvard Medical School and Mass. Eye and Ear. “We show that hair cells can be generated in a damaged cochlea and that hair cell replacement leads to an improvement in hearing.”

In the experiment, the researchers applied a drug to the cochlea of deaf mice. The drug had been selected for its ability to generate hair cells when added to stem cells isolated from the ear. It acted by inhibiting an enzyme called gamma-secretase that activates a number of cellular pathways. The drug applied to the cochlea inhibited a signal generated by a protein called Notch on the surface of cells that surround hair cells. These supporting cells turned into new hair cells upon treatment with the drug. Replacing hair cells improved hearing in the mice, and the improved hearing could be traced to the areas in which supporting cells had become new hair cells.

“The missing hair cells had been replaced by new hair cells after the drug treatment, and analysis of their location allowed us to correlate the improvement in hearing to the areas where the hair cells were replaced,” Dr. Edge said.

This is the first demonstration of hair cell regeneration in an adult mammal. “We’re excited about these results because they are a step forward in the biology of regeneration and prove that mammalian hair cells have the capacity to regenerate,” Dr. Edge said. “With more research, we think that regeneration of hair cells opens the door to potential therapeutic applications in deafness.”

Gene Associated with Active Personality Traits Also Linked to Longevity

A variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life, UC Irvine and other researchers have found.

This derivative of a dopamine-receptor gene — called the DRD4 7R allele — appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.

Robert Moyzis, professor of biological chemistry at UC Irvine, and Dr. Nora Volkow, a psychiatrist who conducts research at the Brookhaven National Laboratory and also directs the National Institute on Drug Abuse, led a research effort that included data from the UC Irvine-led 90+ Study in Laguna Woods, Calif. Results appear online in The Journal of Neuroscience.

The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals’ reactivity to their environment.

People who carry this variant gene, Moyzis said, seem to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors.

“While the genetic variant may not directly influence longevity,” Moyzis said, “it is associated with personality traits that have been shown to be important for living a longer, healthier life. It’s been well documented that the more you’re involved with social and physical activities, the more likely you’ll live longer. It could be as simple as that.”

Numerous studies — including a number from the 90+ Study — have confirmed that being active is important for successful aging, and it may deter the advancement of neurodegenerative diseases, such as Alzheimer’s.

Prior molecular evolutionary research led by Moyzis and Chuansheng Chen, UC Irvine professor of psychology & social behavior, indicated that this “longevity allele” was selected for during the nomadic out-of-Africa human exodus more than 30,000 years ago.

In the new study, the UC Irvine team analyzed genetic samples from 310 participants in the 90+ Study. This “oldest-old” population had a 66 percent increase in individuals carrying the variant relative to a control group of 2,902 people between the ages of 7 and 45. The presence of the variant also was strongly correlated with higher levels of physical activity.

Next, Volkow, neuroscientist Panayotis Thanos and their colleagues at the Brookhaven National Laboratory found that mice without the variant had a 7 percent to 9.7 percent decrease in lifespan compared with those possessing the gene, even when raised in an enriched environment.

While it’s evident that the variant can contribute to longevity, Moyzis said further studies must take place to identify any immediate clinical benefits from the research. “However, it is clear that individuals with this gene variant are already more likely to be responding to the well-known medical adage to get more physical activity,” he added.

A Better Treatment for Neck, Back and Joint Pain

Chronic musculoskeletal pain is the number one cause of chronic disability in North America and chronic back pain is the leading cause of disability in Americans under the age of 45. This rampaging epidemic of pain can conceivably be eliminated in 80-90% of sufferers with prolotherapy. This treatment which relies on the body’s own healing process is performed by specially trained medical doctors. It has been shown to be effective for pain associated with: the back, the neck, all joints throughout the body, arthritis, migraines, fibromyalgia, sciatica, herniated discs, tension headaches, sports injuries, fibromyalgia, loose joints, TMJ Syndrome, tendinitis, sciatica and degenerated joints. Many people have been able to avoid spinal surgery or joint replacement with this much safer and often more effective treatment.

Prolotherapy relies on the body’s own healing process to eliminate pain. Most neck, back and other musculoskeletal pain is due to weakness of ligaments and tendons. Since ligaments and tendons are the connective tissue that hold our muscles to bone, and bone to bone, both must be taut and strong.

Back pain results when weak ligaments and tendons cause the spine to become “unstable.” Vertebrae begin to slip, move and rotate from their proper position, causing pressure on the nerves. Limited results in pain alleviation may be achieved with cortisone and other anti-inflammatory agents but these do not address the cause of the pain. Temporary pain suppression is not a cure for the underlying problem: ligament and tendon weakness. Advocates of the technique say Prolotherapy is the long-term solution to chronic pain because it strengthens the ligaments and tendons so they can move the vertebrae back into their proper places.

Prolotherapy involves the injection of an “irritant” solution such as dextrose, salt solution or cod liver oil into the area where the ligaments have either been weakened or damaged through injury, degeneration or aging. The injection is given at the point where the ligament connects to the bone. With this injection, the Prolotherapy doctor causes the body to heal itself through the process of inflammation.

When an irritant is introduced, at the site of injury, the immune system is summoned to the area. The body begins a healing process exactly where the painful area is located. New fibrous tissue is laid, repairing and strengthening the ligaments so that they can pull the vertebrae back where they belong and alleviate pain.

Prolotherapy treatment sessions are generally given every four to six weeks to allow time for the growth of the new connective tissue. Patients usually require four to six treatment sessions for complete recovery, some experience more immediate results.

Standard medical and surgical procedures cannot match Prolotherapys 80-90% effectiveness in eliminating chronic pain, nor can standard medicine match the relative low cost of treatment. Prolotherapy treatments can range from $100-$500, where a typical surgical procedure may cost over 100 times that amount!

There are currently about 300 physicians who practice Prolotherapy in the United States. With the recent rise in popularity, however, this number is expected to multiply greatly within the next few years. A list of doctors in each state can be found at www.getprolo.com

Do Visible Signs of Aging Predict Heart Disease?

If you look old, your heart may feel old, according to research presented at the American Heart Association’s Scientific Sessions 2012.

In a new study, those who had three to four aging signs — receding hairline at the temples, baldness at the head’s crown, earlobe crease, or yellow fatty deposits around the eyelid (xanthelasmata) — had a 57 percent increased risk for heart attack and a 39 percent increased risk for heart disease .

“The visible signs of aging reflect physiologic or biological age, not chronological age, and are independent of chronological age,” said Anne Tybjaerg-Hansen, M.D., the study’s senior author and professor of clinical biochemistry at the University of Copenhagen in Denmark.

Researchers analyzed 10,885 participants 40 years and older (45 percent women) in the Copenhagen Heart Study. Of these, 7,537 had frontoparietal baldness (receding hairline at the temples), 3,938 had crown top baldness, 3,405 had earlobe crease, and 678 had fatty deposits around the eye.

In 35 years of follow-up, 3,401 participants developed heart disease and 1,708 had a heart attack.

Individually and combined, these signs predicted heart attack and heart disease independent of traditional risk factors. Fatty deposits around the eye were the strongest individual predictor of both heart attack and heart disease.

Heart attack and heart disease risk increased with each additional sign of aging in all age groups and among men and women. The highest risk was for those in their 70s and those with multiple signs of aging.

In the study, nurses and laboratory technicians noted the quantity of gray hair, prominence of wrinkles, the type and extent of baldness, the presence of earlobe crease and eyelid deposits.

“Checking these visible aging signs should be a routine part of every doctor’s physical examination,” Tybjaerg-Hansen said.

Co-authors are Mette Christoffersen, Ph.D. candidate; Ruth Frikke-Schmidt, M.D.; Peter Schnohr, M.D.; Gorm Jensen, M.D.; and Borge Nordestgaard, M.D.

Life Expectancy in the Wild Birds Predicted by Telomere Lengths

seychelles-warblerResearchers at the University of East Anglia have found that biological age and life expectancy can be predicted by measuring an individual’s DNA.

They studied the length of chromosome caps — known as telomeres — in a 320-strong wild population of Seychelles Warblers on a small isolated island.

Published Nov. 20 in Molecular Ecology, their research shows that individuals differ radically in how quickly their telomeres shorten with age, and that having shorter telomeres at any age is associated with an increased risk of death. Telomere length is a better indicator of future life-expectancy than actual age and may, therefore, be an indicator of biological age.

The 20-year research project is the first of its kind to measure telomeres across the entire lifespan of individuals in a wild population.

Telomeres are found at the end of chromosomes. They act as protective caps to stop genes close to the end of the chromosome degenerating — like the hard plastic ends of a boot lace.

Lead researcher Dr David S Richardson said: “Over time these telomeres get broken down and become shorter. When they reach a critical short length they cause the cells they are in to stop functioning. This mechanism has evolved to prevent cells replicating out of control — becoming cancerous. However the flip side is that as these zombie cells build up in our organs it leads to their degeneration — aging — and consequently to health issues and eventually death.

“Telomeres help safeguard us from cancer but result in our aging.”

Researchers studied the warbler population on Cousin Island. Blood samples were collected twice a year and telomere length analysed.

“We wanted to understand what happens over an entire lifetime, so the Seychelles Warbler is an ideal research subject. They are naturally confined to an isolated tropical island, without any predators, so we can follow individuals throughout their lives, right through to old age.

“We investigated whether, at any given age, their telomere lengths could predict imminent death. We found that short and rapidly shortening telomeres were a good indication that the bird would die within a year.

“We also found that individuals with longer telomeres had longer life spans overall.

“It used to be thought that telomere shortening occurred at a constant rate in individuals, and that telomere length could act as an internal clock to measure the chronological age of organisms in the wild.

“However while telomeres do shorten with chronological age, the rate at which this happens differs between individuals of the same age. This is because individuals experience different amounts of biological stress due to the challenges and exertions they face in life. Telomere length can be used as a measure of the amount of damage an individual has accumulated over its life.

“We saw that telomere length is a better indicator of life expectancy than chronological age — so by measuring telomere length we have a way of estimating the biological age of an individual — how much of its life it has used up.”

The research is important because while these ideas have been researched in the lab, they have never been tested in a wild environment.

“It would be virtually impossible to do such a study in humans,” said Dr Richardson. “For one thing it would take a very long time to study a human lifespan. Also in humans we would normally, quite rightly, intervene in cases of disease, so it wouldn’t be a natural study.

“We found that telomeres are linked to body condition and reflect the history of oxidative stress that has occurred within an individual’s lifetime. The healthier you are, or have been, the better telomeres you have. But it’s hard to know whether this is a consequence of being healthy, or a cause.

“Oxidants attack telomeres. So things like smoking, eating foods that are bad for you, and putting your body through extreme physical or mental stress all have a shortening affect on telomeres.

“All these stresses do damage to our bodies. You hear people saying ‘oh they look like they’ve had a hard life’. This is why. A shortened telomere shows an accumulation of damage life has done to you.”

‘Telomere length and dynamics predict mortality in a wild longitudinal study’ is authored by Dr David S Richardson and Emma Barrett from the University of East Anglia (UK), Terry Burke from the University of Sheffield (UK), and Jan Komdeur and Martijn Hammers from the University of Gronigen (Netherlands).

The study was funded by the Natural Environment Research Council (NERC) and carried out in collaboration with conservation group Nature Seychelles.

Eating Egg Yolks Almost as Bad as Smoking?

Egg YolkNewly published research led by Western’s Dr. David Spence shows that eating egg yolks accelerates atherosclerosis in a manner similar to smoking cigarettes.

Surveying more than 1200 patients, Spence found regular consumption of egg yolks is about two-thirds as bad as smoking when it comes to increased build-up of carotid plaque, a risk factor for stroke and heart attack. The research is published online in the journal Atherosclerosis.

Atherosclerosis, also called coronary artery disease, is a disorder of the arteries where plaques, aggravated by cholesterol, form on the inner arterial wall. Plaque rupture is the usual cause of most heart attacks and many strokes.

We suspect that eggs yolks cause increased atherosclerosis because of the way the hens are fed not because there is anything inherently bad about eating the. It is likely a problem similar to the increase in atherosclerosis when people eat beef. The animals are fed large amounts of soy meal and grains which contain much more omega-6 fatty acids than the animals normally eat and close to zero omega-3 fatty acids. As a result the meat and egg yolks are high in arachidonic acid. When consumed by humans that is converted into series 2 prostaglandins which produces inflammation and as a result atherosclerosis and other degenerative diseases.

The study looked at data from 1,231 men and women, with a mean age of 61.5, who were patients attending vascular prevention clinics at London Health Sciences Centre’s University Hospital. Ultrasound was used to establish a measurement of total plaque area and questionnaires were filled out regarding their lifestyle and medications including pack-years of smoking (number of packs per day of cigarettes times the number of years), and the number of egg yolks consumed per week times the number of years consumed (egg yolk-years).

The researchers found carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and egg yolk-years. In other words, compared to age, both tobacco smoking and egg yolk consumption accelerate atherosclerosis. The study also found those eating three or more yolks a week had significantly more plaque area than those who ate two or fewer yolks per week.

“The mantra ‘eggs can be part of a healthy diet for healthy people’ has confused the issue. It has been known for a long time that a high cholesterol intake increases the risk of cardiovascular events, and egg yolks have a very high cholesterol content. In diabetics, an egg a day increases coronary risk by two to five-fold,” said Spence, a professor of Neurology at Western’s Schulich School of Medicine & Dentistry and the director of its Stroke Prevention and Atherosclerosis Research Centre at the Robarts Research Institute.

“What we have shown is that with aging, plaque builds up gradually in the arteries of Canadians, and egg yolks make it build up faster — about two-thirds as much as smoking. In the long haul, egg yolks are not okay for most Canadians.”

Spence added the effect of egg yolk consumption over time on increasing the amount of plaque in the arteries was independent of sex, cholesterol, blood pressure, smoking, body mass index and diabetes. And while he says more research should be done to take in possible confounders such as exercise and waist circumference, he stresses that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease.