Posts Tagged ‘telomere’

by Philip Perry

Researchers at the Salk Institute in La Jolla, California have discovered a way to turn back the hands of time. Juan Carlos Izpisua Belmonte led this study, published in the journal Cell. Here, elderly mice underwent a new sort of gene therapy for six weeks. Afterward, their injuries healed, their heart health improved, and even their spines were straighter. The mice also lived longer, 30% longer.

Today, we target individual age-related diseases when they spring up. But this study could help us develop a therapy to attack aging itself, and perhaps even target it before it begins taking shape. But such a therapy is at least ten years away, according to Izpisua Belmonte.

Many biologists now believe that the body, specifically the telomeres—the structures at the end of chromosomes, after a certain time simply wear out. Once degradation overtakes us, it’s the beginning of the end. This study strengthens another theory. Over the course of a cell’s life, epigenetic changes occur. This is the activation or depression of certain genes in order to allow the organism to respond better to its environment. Methylation tags are added to activate genes. These changes build up over time, slowing us down, and making us vulnerable to disease.


Chromosomes with telomeres in red.

Though we may add life to years, don’t consider immortality an option, at least not in the near-term. “There are probably still limits that we will face in terms of complete reversal of aging,” Izpisua Belmonte said. “Our focus is not only extension of lifespan but most importantly health-span.” That means adding more healthy years to life, a noble prospect indeed.

The technique employs induced pluripotent stem cells (iPS). These are similar to those which are present in developing embryos. They are important as they can turn into any type of cell in the body. The technique was first used to turn back time on human skin cells, successfully.

By switching around four essential genes, all active inside the womb, scientists were able to turn skin cells into iPS cells. These four genes are known as Yamanaka factors. Scientists have been aware of their potential in anti-aging medicine for some time. In the next leg, researchers used genetically engineered mice who could have their Yamanaka factors manipulated easily, once they were exposed to a certain agent, present in their drinking water.

Since Yamanaka factors reset genes to where they were before regulators came and changed them, researchers believe this strengthens the notion that aging is an accumulation of epigenetic changes. What’s really exciting is that this procedure alters the epigenome itself, rather than having the change the genes of each individual cell.


The mechanics of epigenetics.

In another leg of the experiment, mice with progeria underwent this therapy. Progeria is a disease that causes accelerated aging. Those who have seen children who look like seniors know the condition. It leads to organ damage and early death. But after six months of treatment, the mice looked younger. They had better muscle tone and younger looking skin, and even lived around 30% longer than those who did not undergo the treatment.

Luckily for the mice, time was turned back the appropriate amount. If turned back too far, stem cells can proliferate in an uncontrolled fashion, which could lead to tumor formation. This is why researchers have been reticent to activate the Yamanaka factors directly. However, these scientists figured out that by intermittently stimulating the factors, they could reverse the aging process, without causing cancer. The next decade will concentrate on perfecting this technique.

Since the threat of cancer is great, terminally ill patients would be the first to take part in a human trial, most likely those with progeria. Unfortunately, the method used in this study could not directly be applied to a fully functioning human. But researchers believe a drug could do the job, and they are actively developing one.

“This study shows that aging is a very dynamic and plastic process, and therefore will be more amenable to therapeutic interventions than what we previously thought,” Izpisua Belmonte said. Of course, mouse systems and human one’s are far different. This only gives us an indication of whether or not it might work. And even if it does, scientists will have to figure out how far to turn back the clock. But as Izpisua Belmonte said, “With careful modulation, aging might be reversed.”

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There’s always the Magic 8 Ball, but when it comes to determining life expectancy, some people want a little more scientific help. Thankfully, there are some useful tests and calculators to help us figure out how many more years we have left — at least until the Fountain of Youth is available in pill form. With that in mind, here are six ways to help predict whether you should keep on working and paying the mortgage or just blow it all on a big beach vacation.

Treadmill test
Want to know if you’ll survive the decade? Hop on a treadmill. Johns Hopkins researchers analyzed more than 58,000 stress tests and concluded that the results of a treadmill test can predict survival over the next 10 years. They came up with a formula, called the FIT Treadmill Score, which helps use fitness to predict mortality.

“The notion that being in good physical shape portends lower death risk is by no means new, but we wanted to quantify that risk precisely by age, gender and fitness level, and do so with an elegantly simple equation that requires no additional fancy testing beyond the standard stress test,” says lead investigator Haitham Ahmed, M.D. M.P.H., a cardiology fellow at the Johns Hopkins University School of Medicine.

In addition to age and gender, the formula factors in your ability to tolerate physical exertion — measured in “metabolic equivalents” or METs. Slow walking equals two METs, while running equals eight.

Researchers used the most common treadmill test, called the Bruce Protocol. The test utilizes three-minute segments, starting at 1.7 mph and a 10 percent grade, which slowly increase in speed and grade.

Researchers analyzed information on the thousands of people ages 18 to 96 who took the treadmill test. They tracked down how many of them died for whatever reason over the next decade. They found that fitness level, as measured by METs and peak heart rate reached during exercise, were the best predictors of death and survival, even after accounting for important variables such as diabetes and family history of premature death.

Sitting test
You don’t need special equipment for this adult version of crisscross applesauce that uses flexibility, balance and strength to measure life expectancy. Brazilian physician Claudio Gil Araujo created the test when he noticed many of his older patients had trouble picking things up off the floor or getting out of a chair.

To try, start by standing upright in the middle of a room. Without using your arms or hands for balance, carefully squat into a cross-legged sitting position. Once you’re settled, stand up from the sitting position — again, without using your arms for help.

You can earn up to 10 points for this maneuver. You get five points for sitting, five for standing, and you subtract a point each time you use an arm or knee for leverage or 1/2 point any time you lose your balance or the movement gets clumsy.

The test seems fairly simple, but Araujo found that it was an accurate predictor of life expectancy. He tested it on more than 2,000 of his patients age 51 to 80, and found that those who scored fewer than eight points were twice as likely to die within the next six years. Those who scored three points or even lower were five times more likely to die within the same time frame.

Araujo didn’t have anyone under 50 try the test, so the results won’t mean the same if you’re younger. As MNN’s Bryan Nelson writes, “If you’re younger than 50 and have trouble with the test, it ought to be a wake-up call. The good news is that the younger you are, the more time you have to get into better shape.”

Test your telomeres

A simple test may help determine your “biological age” by measuring the length of your telomeres. Telomeres are protective sections of DNA located at the end of your chromosomes. They’re sometimes compared to the plastic tips of shoelaces that keep the laces from fraying.

Each time a cell replicates, the telomeres become shorter. Some researchers believe that lifespan can be roughly predicted based upon how long your telomeres are. Shorter telomeres hint at a shorter lifespan for cells. Longer telomeres may mean you have more cell replications left.

Originally offered a few years ago only as an expensive — and relatively controversial — blood test in Britain, telomere testing in now available all over the world, and some companies even test using saliva. The results tell you where your telomere lengths fall in relation to other participants your age.

The link between genetics and longevity has been so embraced that testing companies have since been founded by respected scientists and researchers including Nobel laureate Elizabeth Blackburn of UC San Francisco and George Church, director of Harvard University’s Molecular Technology Group.

The increase in the number of at-home tests is getting the attention of concerned federal regulators and other researchers who question whether the science should stay in the lab.

“It is worth doing. It does tell us something. It is the best measure we have” of cellular aging, aging-researcher and Genescient CEO Bryant Villeponteau told the San Jose Mercury News. But testing still belongs in a research setting, he said, not used as a personal diagnostic tool.

As more people take them, he said, “I think the tests will get better, with more potential to learn something.”

Grip strength

Do you have an iron handshake or a limp fish grasp? Your grip strength can be an indicator of your longevity.

Recent research has shown a link between grip strength and your biological age. Hand-grip strength typically decreases as you age, although many studies have shown links between stronger grip strength and increased mortality.

You can keep your grip strong by doing regular hand exercises such as slowly squeezing and holding a tennis or foam ball, then repeating several more times.

Take a sniff

Does every little smell bug you? People who wear too much perfume? Grilled fish in the kitchen? A sensitive sense of smell is good news for your lifespan.

In a study last fall, University of Chicago researchers asked more than 3,000 people to identify five different scents. The found that 39 percent of the study subjects who failed the smelling test died within five years, compared to 19 percent of those with moderate smell loss and just 10 percent of those with a healthy sense of smell.

“We think loss of the sense of smell is like the canary in the coal mine,” said the study’s lead author Jayant M. Pinto, M.D., an associate professor of surgery at the University of Chicago who specializes in the genetics and treatment of olfactory and sinus disease. “It doesn’t directly cause death, but it’s a harbinger, an early warning that something has gone badly wrong, that damage has been done. Our findings could provide a useful clinical test, a quick and inexpensive way to identify patients most at risk.”

Life expectancy calculator

There are many online calculators that can serve up you estimated last birthday — thanks to some fancy algorithms. Some only take into account a few simple factors such as your age, height and weight. The better ones consider a range of variables including family health history, diet and exercise practices, marital and education status, smoking, drinking and sex habits, and even where you live.

Enter as much data as you can into an online form, like this one from researchers at the University of Pennsylvania, and click to get your results: http://gosset.wharton.upenn.edu/mortality/perl/CalcForm.html

Read more: http://www.mnn.com/health/fitness-well-being/stories/6-tools-to-help-predict-how-long-youll-live#ixzz3WScKjbUW