Are Telomeres the Key to Aging and Cancer?

 

Do you think we will be able to live forever in the near future?

I think there's a possibility that we may have an indefinite lifespan. I think that's a possibility. At the end of our chromosomes of every cell, there's something called the telomeres. And the telomeres are like a clock. They get shorter every time a cell reproduces. And when the telomere gets so short, it frays, falls apart, and you die. So we have a time limit. We've also discovered telomerase, a chemical that stops the clock. There's a clock in our body that tracks how long we're going to live and there's something called telomerase which stops the clock, so the question is... can we live forever? In our discovery, we also found that cancer uses telomeres and telomerase to live forever. So cancer is immortal in principle and could live forever. So the secret of immortality is tantalizing close. We know that there are cells that make immortality possible, but there's a price to pay. The price to pay is you don't want cancers to also follow you. We have a whole bunch of top people in the sciences and medicine looking for ways to extend the human lifespan without waking up the cancers that cut it short.

~ Michio Kaku, world-renowned physicist

Inside the nucleus of a cell, our genes are arranged along twisted, double-stranded molecules of DNA called chromosomes. At the ends of the chromosomes are stretches of DNA called telomeres, which protect our genetic data, make it possible for cells to divide, and hold some secrets to how we age and get cancer.

Telomeres have been compared with the plastic tips on shoelaces, because they keep chromosome ends from fraying and sticking to each other, which would destroy or scramble an organism's genetic information.

Yet, each time a cell divides, the telomeres get shorter. When they get too short, the cell can no longer divide; it becomes inactive or "senescent" or it dies. This shortening process is associated with aging, cancer, and a higher risk of death. So telomeres also have been compared with a bomb fuse.

What are telomeres?

Like the rest of a chromosome, including its genes, telomeres are sequences of DNA — chains of chemical code. Like all DNA, they are made of four nucleic acid bases: G for guanine, A for adenine, T for thymine, and C for cytosine.

Telomeres are made of repeating sequences of TTAGGG on one strand paired with AATCCC on the other strand. Thus, one section of telomere is a "repeat" made of six "base pairs."

In white blood cells, the length of telomeres ranges from 8,000 base pairs in newborns to 3,000 base pairs in adults and as low as 1,500 in elderly people. (An entire chromosome has about 150 million base pairs.) Each time it divides, an average cell loses 30 to 200 base pairs from the ends of its telomeres.

Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent or die.

Telomeres do not shorten in tissues where cells do not continually divide, such as heart muscle.

Why do chromosomes have telomeres?

Without telomeres, the main part of the chromosome — the part with genes essential for life — would get shorter each time a cell divides. So telomeres allow cells to divide without losing genes. Cell division is necessary for growing new skin, blood, bone, and other cells.

Without telomeres, chromosome ends could fuse together and corrupt the cell's genetic blueprint, possibly causing malfunction, cancer, or cell death. Because broken DNA is dangerous, a cell has the ability to sense and repair chromosome damage. Without telomeres, the ends of chromosomes would look like broken DNA, and the cell would try to fix something that wasn't broken. That also would make them stop dividing and eventually die.

Why do telomeres get shorter each time a cell divides?

Before a cell can divide, it makes copies of its chromosomes so that both new cells will have identical genetic material. To be copied, a chromosome's two DNA strands must unwind and separate. An enzyme (DNA polymerase) then reads the existing strands to build two new strands. It begins the process with the help of short pieces of RNA. When each new matching strand is complete, it is a bit shorter than the original strand because of the room needed at the end for this small piece of RNA. It is like someone who paints himself into a corner and cannot paint the corner.

Telomerase counteracts telomere shortening

An enzyme named telomerase adds bases to the ends of telomeres. In young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, there is not enough telomerase, so the telomeres grow shorter and the cells age.

Telomerase remains active in sperm and eggs, which are passed from one generation to the next. If reproductive cells did not have telomerase to maintain the length of their telomeres, any organism with such cells would soon go extinct.

Telomeres and cancer

As a cell begins to become cancerous, it divides more often, and its telomeres become very short. If its telomeres get too short, the cell may die. Often times, these cells escape death by making more telomerase enzyme, which prevents the telomeres from getting even shorter. Many cancers have shortened telomeres, including pancreatic, bone, prostate, bladder, lung, kidney, and head and neck.

Measuring telomerase may be a way to detect cancer. And if scientists can learn how to stop telomerase, they might be able to fight cancer by making cancer cells age and die. In one experiment, researchers blocked telomerase activity in human breast and prostate cancer cells growing in the laboratory, prompting the tumor cells to die. But there are risks. Blocking telomerase could impair fertility, wound healing, and production of blood cells and immune system cells.

Telomeres and aging

Geneticist Richard Cawthon and colleagues at the University of Utah found shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

While telomere shortening has been linked to the aging process, it is not yet known whether shorter telomeres are just a sign of aging — like gray hair — or actually contribute to aging.

If telomerase makes cancer cells immortal, could it prevent normal cells from aging? Could we extend lifespan by preserving or restoring the length of telomeres with telomerase? If so, would that increase our risk of getting cancer?

Scientists are not yet sure. But they have been able to use telomerase in the lab to keep human cells dividing far beyond their normal limit, and the cells do not become cancerous.

If we used telomerase to "immortalize" human cells, we may be able to mass produce cells for transplantation, including insulin-producing cells to cure diabetes, muscle cells for treating muscular dystrophy, cartilage cells for certain kinds of arthritis, and skin cells for healing severe burns and wounds. An unlimited supply of normal human cells grown in the laboratory would also help efforts to test new drugs and gene therapies.

How big is the role of telomeres in aging?

Some long-lived species like humans have telomeres that are much shorter than species like mice, which live only a few years. Nobody knows why. But it's evidence that telomeres alone do not dictate lifespan.

Cawthon's study found that when people are divided into two groups based on telomere length, the half with longer telomeres lives an average of five years longer than those with shorter telomeres. This study suggests that lifespan could be increased five years by increasing the length of telomeres in people with shorter ones.

People with longer telomeres still experience telomere shortening as they age. How many years might be added to our lifespan by completely stopping telomere shortening? Cawthon believes 10 years and perhaps 30 years.

After age 60, the risk of death doubles every 8 years. So a 68-year-old has twice the chance of dying within a year compared with a 60-year-old. Cawthon's study found that differences in telomere length accounted for only 4% of that difference. And while intuition tells us older people have a higher risk of death, only 6% is due purely to chronological age. When telomere length, chronological age, and gender are combined (women live longer than men), those factors account for 37% of the variation in the risk of dying over age 60. So what causes the other 63%?

A major cause of aging is "oxidative stress." It is the damage to DNA, proteins, and lipids (fats) caused by oxidants, which are highly reactive substances containing oxygen. These oxidants are produced normally when we breathe, and also result from inflammation, infection, and consumption of alcohol and cigarettes. In one study, scientists exposed worms to two substances that neutralize oxidants, and the worms' lifespan increased an average 44%.

Another factor in aging is "glycation." It happens when glucose, the main sugar we use as energy, binds to some of our DNA, proteins, and lipids, leaving them unable to do their jobs. The problem becomes worse as we get older, causing body tissues to malfunction, resulting in disease and death. Glycation may explain why studies in laboratory animals indicate that restricting calorie intake extends lifespan.

Most likely oxidative stress, glycation, telomere shortening, and chronological age along with various genes — all work together to cause aging. Cawthon says that if all processes of aging could be eliminated and oxidative stress damage could be repaired, "one estimate is people could live 1,000 years."

What are the prospects for human immortality?

Human lifespan has increased considerably since the 1600s, when the average lifespan was 30 years. By 2012, the average US life expectancy was nearly 79. Reasons for the increase include sewers and other sanitation measures, antibiotics, clean water, refrigeration, vaccines and other medical efforts to prevent children and babies from dying, improved diets, and better health care.

Some scientists predict average life expectancy will continue to increase, although many doubt the average will ever be much higher than 90. But a few say vastly longer lifespans are possible.

How you can lengthen and protect your telomeres

The good news is that you have a lot of control over the wear-and-tear of your telomeres. And even if you have shorter telomeres, it’s not a done deal — you can lengthen them with certain habits and behaviors. Here’s how to do it:

Since how you perceive your stress counts, finding ways to feel more in control is key. Meditation gives you that time and space to sort out your thoughts, so you can recognize which worries are valid, and which are not. This changes your perception and experience of stress. A 2009 paper suggests that mindfulness meditation lowers stress, which in turn could preserve telomeres. Another study found that women who practiced loving kindness meditation (a technique that encourages compassion) had longer telomeres than women who didn’t. Carve out time each day (put it in the calendar if you have to) to quieten your thoughts and focus on your breath. Even a quick five-minute meditation in the middle of your workday can calm your nervous system and do wonders for your sense of well-being.

Limit exposure to air pollution. If you live near a highway or have a long commute, this one could be hard. But air pollution does affect telomere length. One study found that traffic officers had shorter telomeres than people who worked in an office. Consider investing in a high-efficiency particulate (HEPA) air filter, and sleep with your windows closed if you live near a busy road.

Get active. Yet another benefit of exercise — it reduces oxidative stress and boosts proteins that help stabilize telomeres. In one study, men and women who didn’t exercise much or at all were biologically older by 10 years than those who were very active. But you don’t need to run a marathon or put in hours each day at the gym. People who do moderate aerobic exercise just 45 minutes, three times a week, have telomeres similar in length to marathon runners. According to Dr. Eric Berg the best exercises to slow telomere shortening are high-intensity exercises and aerobic exercises. But take note office workers: “It’s not just how active you are,” says Epel, “it’s really how much sitting you do, so people like me are in trouble. I exercise every day, but I sit on my butt for hours the rest of the time.” Get up regularly from your desk — at least once every hour — and walk around or do some stretching. A standing desk, although pricey, is a great long-term investment in your health.

Maintain a healthy weight. Obesity causes telomeres to wear down quicker. One study found that the loss of telomeres in obese people was equivalent to 9 years of life. One way to keep your weight steady is to practice intermittent fasting — when you cycle in and out of periods of eating and not eating. Intermittent fasting not only boosts weight loss, it makes cells more resilient and promotes cellular repair. It also lowers oxidative stress — when free radicals overpower the antioxidants in the body. Since oxidative stress shortens telomeres, reducing this type of stress will help preserve them.

Boost your NAD+ levels. Nicotinamide adenine dinucleotide (known as NAD+) is a coenzyme, found in every cell, that rewires your metabolism and activates sirtuins — proteins that help maintain the length of your telomeres. Since NAD+ levels drop as you get older, consider taking supplements of this coenzyme or practice intermittent fasting, which increases NAD+ supplies.

Load up on healthy fats and veggies. One study found that telomeres didn’t shorten as quickly in people with high levels of omega-3 fatty acids than people with low levels of the fats. Another study found that women with shorter telomeres and lower levels of vitamin C, vitamin E, and beta carotene had an increased risk of developing breast cancer. Eat plenty of lightly cooked leafy greens and broccoli, berries, wild salmon, and other fatty fish. “Eat your damn vegetables,” says Michael Fossel, MD, PhD, author of “The Telomerase Revolution”. “It’s really not rocket science when it comes to maintaining telomeres.” But he emphasizes that moderation is key: “You need a good diet, but if what you do is end up stressing yourself worrying about it the whole time, you’ll just undercut yourself. Chill out, relax, go meditate.”

Give TA-65 supplements a try. Made from a Chinese root, this supplement claims to activate telomerase — the enzyme that rebuilds telomeres. A 2009 study found that TA-65 increased telomere length and lessened DNA damage in mice. But before you rush out to buy it, it doesn’t come cheap — expect to shell out $600 for a three-month supply. A slightly cheaper option is cycloastragenol — believed to be the active ingredient of TA-65. One study found that, like TA-65, it activated telomerase in mice.

Test your telomeres at home. You can now order telomeres testing kits in the mail. With the prick of a finger or swab of a cheek, companies like TeloYears and Titanova tell you how your telomeres compare in length to others your age. Whether the information is accurate is another story — people have received conflicting results when trying different tests. Most scientists agree that while knowing your telomere length could nudge you to adopt healthier habits, there are still too many unknowns. For instance, it’s not clear whether telomeres are the same length throughout all tissues and cells of the body. So a test that analyses telomeres in saliva may be offering just a small snapshot of the bigger picture. Tests typically cost around $100 a pop — money perhaps better spent on a fresh farmer’s market haul or new walking shoes.

from learn.genetics.utah.edu and daveasprey.com/telomeres-aging