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Telomeres hold clues to aging gracefully


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LIFEMAG Original

Telomeres hold clues to aging gracefully

by Alexandra Taylor Published on 16th Sep 2015

by Alexandra Taylor Published on 16th September 2015

As the only variable portion of the human genome, telomeres hold great promise for human longevity research. Several exciting recent studies have highlighted the role they play in aging. What are these tiny telomeres, and how do they fit into the big picture?

Protective Coating

Our genetic information is present in the series of bases that make up our DNA, wrapped into chromosomes. Telomeres cap the ends of our chromosomes to help stabilize them. They are often likened to the plastic caps on the tips of shoelaces – they help keep the ends of DNA strands from fraying. Without telomeres, the cell might confuse the end of a chromosome for a piece of broken DNA and attempt to repair it. This could lead to cell death, cancer, and other complications.

When a cell divides, it makes a copy of all the genetic information in the chromosomes. This includes the telomeres, which are made up of about 9,000 repeating bases in a human newborn. However, the copying machinery is imperfect; during each division, about 30-200 bases are lost from the telomeres. Each cell divides 50-70 times in its lifetime, and each consecutive strand of DNA is shorter than the last. The telomere of the average human adult contains only about 3,000 bases.

Shorter telomeres are associated with age-related diseases and lower life expectancy. Researchers are investigating the role that telomere length plays in the aging process, and whether these effects could be reversible.

Exacerbating Aging

Science has shown that shorter telomeres are related to lower life expectancy. In 2003, a study at the University of Utah found people over the age of 60 with short telomeres were three times more susceptible to heart disease and eight times more vulnerable to infectious disease. A 2010 study published in the Journal of the American Medical Association linked short telomeres with a three-fold risk of developing cancer over the next decade.

This February, researchers at Stanford University published the results of their study of turquoise killifish in Cell. Turquoise killifish have a highly condensed lifespan that makes them useful for aging studies. Researchers silenced the gene responsible for building telomeres, known as TERT. The fish experienced age-related maladies early on in their development, although their lifespans were not affected. The lack of capped chromosomes played an obvious role in the aging process.

These results seem promising and call for further research. As Carl Zimmer noted in the New York Times, any drug that could extend the lifespan of these fish by even a small amount could hold major potential for human longevity.

Stress Response

In 2009, Dr. Jack Szostak, Dr. Elizabeth Blackburn, and Dr. Carol Greider received the Nobel Prize in Physiology or Medicine for their “discovery of how chromosomes are protected by telomeres and the enzyme telomerase.” Telomerase adds DNA back to the ends of chromosomes, making up for some of the loss in telomere length. In most cells, however,  telomerase levels decrease with age, making it less effective over time.

Dr. Blackburn researched the effects that physiological stress can have on telomere length. She tested samples taken from mothers with sick children and wives of dementia patients. The longer the women had been in these situations, the shorter their telomeres. Stress had caused their telomerase activity to decline, leaving them more vulnerable to telomere shortening, thus hastening the aging process.

A difficult family situation is one of many influences that can cause telomere shortening. An observational study published this summer in PLoS One compared telomere length, and thus biological age, with feelings of stress about one’s neighborhood. People in the Netherlands who lived in a particularly bad area were shown to be biologically older than their more secure counterparts by about 12 years—a staggering difference.

Stress has long been thought to contribute to aging. These findings underscore the importance of mental wellbeing to overall health. Telomere shortening leaves individuals vulnerable to heart disease, Alzheimer’s disease, cancer, and diabetes, among others.

Uncontrolled Growth

Increased telomerase activity has been linked to cancer, a hurdle that researchers must now confront. By replacing lost portions of DNA, the enzyme increases the number of times a cell can divide. Uncontrolled cell growth is often symptomatic of a tumor. Any treatment that uses telomerase to extend lifespan could leave the patient at an increased risk of cancer.

At the same time, telomerase offers a promising avenue for cancer research. If scientists can figure out how to stop telomerase from working, they can theoretically cut off cell division in a tumor. This must be done selectively, or risk compromising the immune system.

At the beginning of this year, researchers at the Stanford University School of Medicine announced that they had successfully extended the telomeres in human cell cultures. These cells are difficult to grow in a lab because of the limited  number of times they can reproduce. This new method will make it much easier to culture human cells for drug and disease research. Even better, the lengthening effects are temporary. In other words, there is a potential for medical application without the risk of cancer.

Personal Best

As we learn more about the role of telomeres, we find more ways to combat the effects of telomere-related aging. Stress relief, exercise, weight loss, and a healthy diet are all old news, but they bear repeating. A 2014 study in the British Medical Journal looked at the eating habits of 4,700 women over 20 years. Researchers found that the closer the woman’s eating habits aligned with the Mediterranean diet, the longer her telomeres. As the lead author, Marta Cous-Bou, told the New York Times, “a three-point change in the adherence score [out of six] is equivalent to 4.5 years of aging, a difference comparable to that between smokers and non-smokers.”

Swedish scientists tracked the influence of a sedentary lifestyle on telomere length. While more time spent sitting was associated with shorter telomeres, they found little correlation between exercise and telomere length. Mortality rates declined the more time subjects spent standing. These results suggest that longer bouts of low-impact movement may be more beneficial than condensed, high-impact workouts for fighting the effects of aging.

Blood Testing

Several companies offer telomere testing for people who want to check their biological age. One such company is Telomere Diagnostics, Inc., cofounded by Nobel recipient Elizabeth Blackburn. The test costs $200 and requires a doctor’s participation. It is not intended to diagnose a particular disease, but to serve as a red flag if something is awry. “It’s not a crystal ball to tell you how many years you’ve got left or any such nonsense,” Dr. Blackburn told the New York Times.

Despite all her expertise in the field, Dr. Blackburn’s venture has been met with criticism, including from fellow Nobel winner Carol Greider. Detractors have argued that too much individual variation among patients makes it difficult to obtain meaningful results. An uncommon reading could expose healthy individuals to a deluge of unnecessary testing.

One Piece of the Puzzle

Although telomeres correlate with many age-related chronic conditions, they may not explain the underlying cause. Telomeres alone do not dictate lifespan: humans have much shorter telomeres than mice, but live much longer. Dr. Richard Cawthon of the University of Utah estimates that telomere length combined with chronological age and gender contribute only 37% to a person’s chances of dying after the age of 60. Other factors include oxidative stress, exacerbated by inflammation, infection, and consumption of cigarettes and alcohol; and glycation, which may be improved by restricted calorie intake. Still, Dr. Cawthon believes that stopping telomere shortening entirely could extend the human lifespan by 10-30 years.