Is this enzyme the elixir of youth?by Nicky Pellegrino
Want to live longer? An enzyme that helps cells maintain themselves could be the answer to slowing or even reversing the ageing process – and there are several other things you could try.
Well, maybe. US scientists Elizabeth Blackburn and Elissa Epel believe it’s possible to influence the way we age at a cellular level. Both are involved in the relatively new field of telomere science and are the authors of a new book, The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer, offering advice tailored to increase the “health span”, if not the lifespan.
Blackburn, a molecular biologist, discovered how telomeres work when experimenting with pond scum in 1984. After a lot of follow-up experiments, she won the Nobel Prize for the discovery in 2009. Often compared with the hard plastic tip on a shoelace, telomeres are structures of DNA at the end of our chromosomes. Every time a cell divides, its telomere shortens, until finally the cell is unable to divide any further and becomes senescent – when the cell becomes old and can no longer renew itself. In The Telomere Effect, the authors compare senescent cells to rotten apples in a barrel.
This has serious consequences for your health. When you have too many senescent cells in your bloodstream, your immune system becomes compromised; too many in the walls of your blood vessels and your arteries stiffen; too many in your skin and it becomes thin. Therefore, the shorter your telomeres are, the higher your chance of dying of a chronic illness such as diabetes, heart disease and even some cancers.
At her lab at the University of California, San Francisco, Blackburn made an important discovery: in some conditions, the telomeres in pond scum actually grew longer. She saw the same thing happen in yeast cells and was intrigued. It turned out there was an enzyme at work – which Blackburn’s lab named telomerase – that can maintain a telomere by building it back up each time a cell divides. Cells with enough telomerase appeared to maintain themselves indefinitely.
Intervening in the ageing process
So is telomerase the elixir of youth? Well, maybe. Efforts to use it to treat human ageing and disease have progressed very slowly. In 1990, a biotech company called Geron was founded, with the purpose of finding a way to intervene in the ageing process. Scientists there were convinced telomerase was the key and focused on finding out more about how it worked.
There were encouraging results working with cells in the lab, and subsequently other researchers have regrown the telomeres in mice. To date, no trials have been done with humans, although that may be about to happen.
Meanwhile, it is possible to buy plant-based telomerase nutritional supplements and creams, but Epel isn’t recommending them at this point.
“Some people report positive effects, but the supplements haven’t been well tested to see any health effects, beyond one year,” she says. “There is a possibility that they may increase the risk of cancers. So it’s unknown territory.”
For now, a safer approach seems to be controlling the lifestyle factors believed to influence telomere length, and chief among those is stress.
In 2004, Epel, a health psychologist at the University of California, San Francisco, teamed up with Blackburn to look at telomere length in a group of mothers who were caring for children with chronic conditions. Examining white blood cells from these women and from a control group of mothers with healthy children, they discovered that those who perceived themselves to be under the most stress were the ones with the lowest levels of telomerase and the shortest telomeres.
Their research showed the fighters of the immune system – CD8 T-cells – were particularly vulnerable to stress. When these grow old, they begin to send out protein molecules that create inflammation throughout the body. This is linked to so many aspects of the ageing process that it’s been dubbed inflamm-ageing.
When you know that childhood trauma shortens the telomeres and that a mother’s psychological state affects her developing baby’s telomere length, it all gets, well, stressful.
Epel cautions that everyday pressures are not the problem here. “Just feeling stressed, having a stressful period at work for instance, is common and natural, and not enough to shorten telomeres,” she says. “Toxic, long-lasting stress is what appears to shorten them.”
Interestingly, some of those mothers of sick kids reported experiencing less stress and had longer telomeres, although their situation was just as difficult. Why? Further tests have shown that what matters is how we respond to a stressful situation; whether we feel threatened or challenged by it. Those with a “bring it on” mentality had longer telomeres than those who felt anxious and panicked.
Epel’s own strategies
“I, myself, am a caregiver,” says Epel, who was part of a family team looking after her late nephew, who was born profoundly brain-damaged. Her own child has also since had some problems.
“I have learnt certain tools that help. That doesn’t mean my life is easy. For everyone, stress resilience is about finding a balance. It’s rare that you find it and keep it and things are stable and easy. It’s more common that you’re doing a balancing act every day.”
Most parenting is stressful to some extent, but when you have a sick or emotionally sensitive child, it is particularly important to develop strong coping mechanisms.
“The hardest part for me was feeling pain when my child feels pain,” says Epel. “That is every parent’s challenge, but when you have an ‘orchid’ [highly sensitive] child and they are often feeling emotional pain, and you can’t fix things and control things, this takes a different type of coping. Some of the skills and wisdom from mindfulness training are particularly important for situations in life you cannot change.”
Epel’s strategies include regularly doing hatha yoga and getting enough sleep. “And social support is one of the strongest stress buffers. It’s important to at least sometimes be with people with similar life experiences, which reminds you that you’re not alone.”
She believes the earlier we develop a healthy response to life’s pressures, the better. “We don’t learn stress-resilience skills in school – about emotional intelligence, about the nature of the mind, about how emotions are made and regulated. But we should. These are critical life skills.”
Telomerase-boosting strategies Epel and Blackburn suggest include meditation, mindfulness-based stress reduction and yoga, in particular Kirtan Kriya, which involves chanting and the tapping of fingers. When the caregivers practised this for 12 minutes a day for two months, they increased telomerase by 43% and decreased gene expression related to inflammation. The Chinese moving meditation qigong has also been shown to increase telomerase.
Day-to-day behaviour makes a difference. “If you are sedentary, you are more vulnerable to stress,” Epel says. “Sedentary stressed people tend to have shorter telomeres than active stressed people. If you have a sleep debt, you also have a big stress response.
“In one of our studies, older women who had a lot of stress had telomere shortening in just one year. But those who had a lot of stress but were also eating well, being active and sleeping enough did not shorten over that year.”
Effects on children
Early-childhood neglect and trauma also have long-lasting cellular effects. The more adversity you experience in childhood, the shorter your telomeres as an adult. Being well cared for, on the other hand, is associated with healthy telomeres.
That doesn’t mean helicopter parenting is the answer – some adversity in childhood is necessary to help us build resilience and develop a challenge response.
“So we need to protect our children from toxic stressors – bullying, exposure to violence or food insecurity,” says Epel. “And we need to be supportive and help them problem-solve the small stressors, the situations that they have the resources to cope with.”
Many other aspects of our life shape our telomeres. Most of the advice Epel and Blackburn have extracted from the research is of the type we are used to hearing and most likely already doing: eat a wholefood diet rich in vegetables and oily fish, avoid sugar and saturated fat, get enough sleep and exercise.
“However, it’s not just our health behaviours, but also the quality of our relationships,” advises Epel. “There are aspects of our psychological and social world that are associated with longer telomeres. For example, being conscientious is associated with longer telomeres, being impulsive or hostile is associated with shorter telomeres. Also, the chemicals we are exposed to on a regular basis, such as high air pollution, are related to our telomere length. For each person, the thing they can do that has the most impact depends on their personal lifestyle, their daily routines.”
Testing artificial telomerase
Not everyone agrees that lifestyle factors are going to make changes on a cellular level that are significant enough to hold off the diseases of old age.
Telomerase therapy advocate Michael Fossel describes the approach as “a pleasant scientific delusion”. He argues that testing the length of the telomeres of peripheral white blood cells tells you only about the state of the immune system and not what’s going on in the coronary arteries, brain or joints.
Fossel, a former professor of clinical medicine at Michigan State University, draws a New Zealand analogy, saying: “It’s like measuring seismic activity in the Bay of Islands to predict earthquake risk in Christchurch.”
Epel and Blackburn argue that the telomere length of white blood cells indicates what is going on in other tissues and that the immune system is tied into many diseases, but Fossel aims to call in the big guns to make a difference at a cellular level. For many years, he has been focused on using synthetic telomerase as a therapeutic tool, and now he is gearing up to begin a $2 million clinical trial to see if it can be used to treat Alzheimer’s.
Similar studies in genetically engineered mice have had encouraging results – Harvard researchers managed to repair damaged tissues and reverse the ageing process. Now Fossel, whose trial is aiming to get Food and Drug Administration approval, intends to deliver the enzyme directly to the brains of 12 people via a lumbar puncture to see if it has the same effect on humans.
Unfortunately, bombing cells with artificial telomerase may provide fuel for the kind of uncontrolled growth that is a hallmark of cancer. Fossel believes the risk is low – in fact, telomerase may well prevent many cancers – but he doesn’t yet have the data to prove it, which is one of the reasons he is targeting the glial cells of the brain.
“There is no treatment for Alzheimer’s whatsoever,” he points out. “If I had it, I’d take the risk.”
Fossel isn’t interested in the root cause of ageing but in the most effective point of intervention, and he is convinced resetting telomere length is it.
And yet there are many other things going on in the human body with the ageing process, and numerous other approaches to slowing it down.
Calorie restriction and drugs
One area of interest is calorie restriction. This activates sirtuins, a class of proteins that are one of the body’s survival tools as they help the cells work more efficiently in times of stress.
“From an evolutionary perspective, this allows a species to survive famine,” says geriatrician Hamish Jamieson, a senior lecturer at the University of Otago.
In animal studies, calorie restriction has been shown to increase the health span, but eating less to live longer hasn’t yet been proved effective and safe for humans.
“There is research to try to mimic the changes and activate the sirtuin [protein that helps regulate the ageing and death of cells] pathway with drugs,” says Jamieson. “The best activator has been found to be resveratrol, a compound found in red wine and blueberries. And the drug that seems most promising is metformin, which is used to treat type 2 diabetes and lowers the liver’s production of glucose.”
There is also interest in another drug, rapamycin, which is used to prevent rejection after organ transplants. This has been shown to extend the lifespan of mice, but hasn’t yet been proven to slow the ageing process. Since it weakens the immune system, it may not be practical for use in humans who, unlike lab mice, don’t live in sterile conditions.
“The medications are going to take years to come to fruition,” says Jamieson. “Meanwhile, the best approach is healthy living. More and more research is showing its impact in ageing.”
Big data studies are adding to our knowledge. New Zealand was the first country to implement interRAI, a comprehensive clinical assessment tool for aged care that will provide a huge amount of information on everything from the impact of loneliness and isolation to side effects from medication use. It was introduced from 2015 – but there was a progressive roll-out before then.
Silicon Valley has got in on the act, with Google-owned life-extension company Calico bringing together scientists from fields as diverse as drug development, genetics and computational biology to develop ways to slow the ageing process. Part of their research so far has involved looking at proteins in the blood that change as we age and are believed to contribute to the deterioration of body tissues.
Epel’s focus is on crowdsourcing data from “citizen scientists” and she is inviting people to sign up to her Track Your LYF project (LYF stands for Live Younger & Fuller – find out more at trackyourlyf.com) to share information.
She and Blackburn recognise that telomeres are just a part of the ageing process, but both are convinced they are one aspect we do have some control over.
“We can’t help it if we have short telomeres from our past – our choices today are what matter most,” says Epel. “Even in the elderly, health behaviours are associated with better telomere stability.”
Their mantra: “Your cells are listening to you.”
Testing your telomeres
A number of companies offer to tell you your cellular age based on telomere length using a simple cheek-swab sample. So is it worth getting tested? Epel sees no harm in it, although she isn’t convinced that at this point you will learn anything very useful.
“You might view it as a big experiment,” she says, “because this is a new area, and we don’t know how accurate the results are yet or what different patterns of telomere-shortening mean.
“For example, what if you have long telomeres and you shorten more quickly than someone with short telomeres? This is a well-known observation in the research studies: long telomeres shorten more quickly. That’s probably not a bad situation, because you have such long telomeres.”
Eating for cell health
- The body is rather like a car, says geriatrician Hamish Jamieson, in that it ages proportionally to how many kilometres it does, how you look after it and what fuel you put into it. His nutrition tip is to eat lots of nuts, as they have been consistently shown to lower inflammation. One big epidemiological study showed that consuming them regularly is associated with significantly lower rates of death.
- The higher the level of omega-3s in the blood, the less telomere-shortening over the next five years. So oily fresh fish, flaxseed oil, leafy green vegetables and walnuts are all beneficial.
- Some studies have found vitamin D is related to longer telomere length, so if you’re concerned you’re not getting enough from sunlight and food – good sources are oily fish and egg yolks – then you might want to consider a supplement.
- You can still enjoy a flat white. Only one trial has been done on telomere length and coffee, and that was with patients who had chronic liver disease. Those who drank four cups a day for a month had longer telomeres than those who refrained altogether.
The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer, by Elizabeth Blackburn and Elissa Epel (Hachette, $37.99)
This article was first published in the May 6, 2017 issue of the New Zealand Listener.
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