This story was first published on November 12, 2022 and has been resurfaced as the Listener brings back its best health features.
The keys to good health well into old age are in our hands, says a youthful scientist who advocates diet and exercise – and a little of what’s “bad” for us.
On the hottest day of September in 1991, eight adult volunteers sealed themselves into a three-acre geodesic glasshouse in the red earth of Oracle, Arizona. The four men and four women, self-confessed hippies, had day jobs in experimental theatre, farming and furniture-making, but their shared mission was to create an exact ecological replica of the Earth, complete with forests, deserts and even a living coral reef. It was called Biosphere 2.
Several strange things happened in the two years they spent locked inside this sci-fi complex – oxygen deprivation, warfare between two groups, and a desperate lack of food – but there was something else going on in the rainforest biome. Free of pesticides and wind, trees grew quickly and lusciously. Yet, despite their near-perfect conditions, once mature, they toppled over and died.
The problem wasn’t overwatering or a virus. It was stress, or more specifically a lack of it. Without wind, the trees were unable to grow “stress wood”, an important part of the ageing process that hardens the tree trunk and supports its full size.
In his bestselling book Jellyfish Age Backwards: Nature’s secrets to longevity, Nicklas Brendborg, 27, a rising star in molecular biology with an MA in biotechnology from the University of Copenhagen, says stress is one of the keys to living a long and healthy life. This is not the stress of working long hours and being busy: it’s the specific tension we place on our cells when we give them small doses of toxins or “survivable stressors”. Cells in recovery are better at repair and maintenance, reduce bodily inflammation, and improve blood sugar regulation.
The scientific word for this process is hormesis. Brendborg says it may explain why a study of Taiwanese apartment dwellers accidentally exposed to background radiation from contaminated steel found they had fewer cases of virtually all types of cancer than the general population. In the US, studies have found that people living in areas with higher-than-usual background radiation levels live longer than average. Hormesis could also explain why blood donors live longer by losing blood, reducing their levels of iron in the process (more on that later).
One way to induce hormesis is through diet. Edible plants release toxins that are harmful to us in high doses, but in moderation work as an effective cellular wake-up call. Foods high in polyphenols, such as chillies, artichokes, pineapples, onions and wild almonds (the latter containing traces of cyanide), all challenge our system at the right dosage.
In his book, Brendborg suggests another way to activate hormesis that has a striking effect on longevity, with a study showing those who do it regularly are 80 per cent less likely to die prematurely. It involves a complex combination of dramatically raising our heart rate and blood pressure, burdening muscles and bones, and increasing the production of free radicals – what Brendborg refers to as the cellular version of a “bull in a China shop”. This potent mix of hermetic stress is exercise, and it’s one of the most powerful anti-ageing drugs available.
Racing the clock
It’s impossible to talk about longevity without addressing the elephant in the room: who wants to live long if you are unable to enjoy the extra time? No one wants to be in the body and mind of a centenarian for an extra 50 years.
On a Zoom call from his native Copenhagen, Brendborg tells the Listener that even if we could cure major diseases such as cardiovascular conditions, it would add only four years to our life expectancy, because we’d die of something else age-related instead. “If you really want to go a long way [towards curing age-related diseases], you have to tackle the real problem, which is the ageing, not the disease,” he says.
Scientists are particularly interested in how we can slow down or even stop the ageing process. This could function like a scoop net, effectively eradicating Alzheimer’s, heart disease and most cancers. But to get to this point we need to know two things: how we measure age, and what causes it. According to Brendborg, scientists are still figuring this out – but we’re getting close.
One of the challenges facing biomedical researchers is their own race against the clock. Researching medicine in this field takes decades to produce results, if not longer. To solve this problem, scientists developed the “epigenetic clock”. By taking a sample of blood or tissue, they can measure the age of your cells, organs and tissues and compare it with your chronological age. You may have 52 candles on your cake, but your epigenetic clock might be 74, and this correlation can predict your likelihood for age-related diseases and even how long you might live.
Questioning why we age at all sounds like an existential question, but it’s also a deeply scientific one. Brendborg writes that most scientists believe that as we get older, our bodies are worse at repairing damage and it “opens the door” to age-related disease. The second, more contentious, thought is that our cells are “programmed” to age, moving through each stage of life as if on a conveyor belt. What if we could halt, or even reverse, the conveyer belt at age 30?
Back to kindergarten
It sounds like sci-fi, but somewhere off the coast of the Mediterranean this Benjamin Button storyline has been going on for thousands of years. Turritopsis, the “immortal” animal in Brendborg’s book title, is a fingernail-sized jellyfish that floats around eating plankton. When stressed, it heads to the ocean floor and returns to a polyp stage, with no physiological sign of ever being older – or as Brendborg puts it, like us “having a stressful day at work and deciding to revert back to being a kindergartener”.
In the right conditions, turritopsis could do this biological magic trick forever. Although most of us wouldn’t choose to be a toddler again, there is a not-so-distant future where our cells could be born again.
Brendborg says to picture one of your chromosomes as a shoelace. Then picture the plastic caps, aglets, on the end of the shoelace that prevent it from fraying. Our telomeres act like aglets, capping the ends of our chromosomes and protecting our DNA. We know that as we age, these “caps” get shorter, and short telomeres are linked to most age-related diseases. The ageless jellyfish, and other cancer-defying animals, including lobster and naked mole rats, all appear to have one thing in common: they can repair their telomeres.
We don’t have control over the length of our telomeres yet, despite one woman receiving gene therapy to produce telomerase – a protein to repair them – in a controversial experiment in Colombia in 2015. As with all things related to nature, everything has a counterweight, and telomerase enables cancer cells to divide indefinitely, so her experiment could prove deadly.
Despite this, Brendborg argues that when it comes to longevity, our genes are largely overrated. There is no single gene for longevity or health – just because your grandmother lived to 103, it has little-to-no effect on your own lifespan. You are more likely to live a similar lifespan to your spouse, and researchers believe this is because we tend to marry someone with a comparable lifestyle.
However, we may be predisposed to diseases that incur ageing. He points to a variant of the apolipoprotein E (APOE) gene that’s associated with Alzheimer’s. Genetic variants that link to a strong immune system seem to correlate with longevity, and there’s a connection to metabolism and growth signals that, among other things, dictate how tall or – in the case of a long life – short you are. But, Brendborg says, “Your lifespan is not very genetically determined at all. That’s good news if you want to do something about how long you’re going to live.”
Fibre and garlic
Asked what surprised him the most in his PhD research that became the book, Brendborg points to the “shaky ground” that much of the dietary advice for health and longevity lives on, especially what’s sold online. He takes aim at antioxidants. Once the beacon of the health world, antioxidant supplements can actually lower life expectancy. In neutralising free radicals, these supplements sedate the “bull in the China shop” and interfere with the process of getting stronger and healthier from exercise. They cancel out hormesis.
Similarly, iron and vitamin D supplements are off the table. If we look at the health of regular blood donors, lowering iron stores might be a good thing. “Excess iron turns up in a number of ghastly circumstances,” he says.
Research shows abnormal amounts of iron in diseased areas of the brain in people with Alzheimer’s and Parkinson’s disease, and it also turns up in the plaque of blood vessels that causes strokes. In trials, cancer cases were 35 per cent lower in people who had their blood drawn regularly. Brendborg is quick to point out lower iron levels can be dangerous for those who may require more iron, such as premenopausal women.
“In the case of vitamin D, we really have to put on rose-coloured glasses to find a benefit.”
It’s the same with omega-3 fish oils and red wine – while good for us in moderation, they are probably connected to longevity because of causation: those who enjoy salmon with a glass of claret are usually wealthy. People who are better off have access to healthcare, less obesity and better diets and are likely to live longer anyway.
In the New Zealand context, our overall life expectancy may be being dragged down by high rates of child poverty.
Throughout the book, Brendborg hesitates to add to the “noise” of anti-ageing dietary recommendations, though there are two that have compelling evidence to support their regular use: garlic and dietary fibre. Fibre, in the form of wholegrains, beans and fruits such as apples and pears, and garlic aid longevity by lowering blood pressure and cholesterol, among other benefits.
He says it’s not a good idea to compare the body with a machine, but gives an analogy about priming a machine with oil. “Of course, there’s a good amount of oil, but once you go overboard, it becomes harmful. And it’s basically the same with us. If you really want to make progress [in health], you can’t just be like, ‘Oh, I’m going to take everything and just get every level high.’ It’s more about, ‘Am I missing something?’ Then, maybe, you can learn what the correct value is and try to hit that value instead of putting your foot on the gas pedal.”
Flossing for life
Halfway through our conversation, he disappears from screen briefly and returns with an armful of plastic dental floss packets. “I get sent these all the time,” he laughs. It’s because he has every dentist’s favourite chapter in the book, “Flossing for Longevity”.
We know that Alzheimer’s disease is characterised by the appearance of protein plaques in the brain. These plaques consist of a peptide called amyloid beta, or, as he helpfully describes them, “little clumps”. The jury is still out on what exactly amyloid beta does, but there is a growing connection between these “clumps” and how they form a defence around bacteria. Bacteria that cause the gum disease periodontitis are found in the brain tissue of deceased Alzheimer’s sufferers, and inside blood clots. Brendborg points to studies that show people in their sixties with gum disease had a greater risk of developing dementia two decades later.
Viruses also biologically age us by wreaking cellular havoc. A small British study has suggested that cognitive impairment from a severe Covid infection can age us 20 years. Brendborg notes that a chronic and common virus called cytomegalovirus (CMV), a member of the herpes family, accelerates ageing. Half of young adults in New Zealand are infected with CMV without knowing it, as it hides out in our system before reactivation. One of the ways it ages us is by refusing to let cells die in a regular process called cellular suicide. Instead, cells become stranded in what Brendborg refers to as a zombie state, spewing out a cocktail of molecules. There is no vaccine for CMV yet, but in the meantime flossing regularly, getting vaccinated for Covid, and having good hygiene are all effective anti-ageing practices.
Mind over matter
Back to Biosphere 2. Despite its label as a failed experiment, all members of the scientific team emerged with lower blood cholesterol, lower blood pressure and better immunity than before they entered the biodome, and researchers believe this could be due to the lack of food. Time-limited calorie restriction (also known as intermittent fasting) can prolong life in certain worms and mice but is yet to be proven in humans.
Brendborg points out that any longevity evidence for fasting is not quite there yet, but theories posit hormesis or autophagy – the cellular “rubbish system” that removes damaged molecules and takes them to the bodily recycling station, as he describes it.
“Eating a healthy diet, exercising, and experimenting with your lifestyle will get you a long way. But it won’t take you to the finish line,” he writes.
Loneliness is one of the factors most strongly associated with an early death. Studies show that people who feel younger than their actual age, and optimistic people, tend to live longer. Despite our complex biological make-up, “our mental state is in the driver’s seat of the body”.
Right now, there are billionaires in Silicon Valley investing huge money into anti-ageing medicine. Brendborg says there are already trials in place to develop anti-ageing drugs that could be as simple as a pill. “Business-wise, it makes sense. Everyone ages, so everyone would potentially be your customer. But really, for the good of humanity, ageing is the source of a lot of suffering, so you can help a lot of people.”
But, I ask, do we really want a bunch of 200-year-olds wandering around in the future? “That’s definitely a philosophical question,” he says. “But I think it’s going to be a good thing.”
With such optimism to call on, this bright young scientist might just live forever.
Heed the warning signs
The Dunedin Study has shown a close link between life experience and the pace at which we age, Veronika Meduna writes.
As we get older, it can be comforting to think of age as just a number. But it’s also true. We all know someone who looks years younger than their chronological age – and, of course, the reverse happens to some people.
Now the Dunedin Study, which has been following 1000 people born in the city 50 years ago, is delivering new insights into why the pace of ageing differs widely between individuals. It has found that ageing processes are well under way by the time people reach their 30s, decades before any age-related symptoms appear.
The speed at which we age depends in part on early life experiences, and our ageing trajectories become clear by mid-life, says study director Richie Poulton. “In the past, researchers tended to focus on the life stages associated with the greatest amount of developmental change – childhood and towards the end of life. The middle adult years were largely ignored. This gaping hole in our understanding signalled a huge opportunity to contribute new insights and knowledge, and we went hard at it.”
Since the study began half a century ago, participants have been taking part in a suite of comprehensive assessments every few years, recording everything from physical and mental health to social circumstances and life experiences. An astonishing 94% of members continue to flock back to the city from wherever they live for these assessments, and thanks to strict anonymity, they have been frank when contributing information about traumatic experiences. Among the tests they take are several biomarkers monitoring physiology and organ function – including the heart, lungs, blood pressure, inflammation, cholesterol and body mass index – to see how they age. The variation in ageing by mid-life can be shocking, says Terrie Moffitt, the study’s associate director and a psychology professor at Duke University, North Carolina.
When participants returned for their 45th birthday assessment, some had been ageing by two years for every chronological year. In contrast, others were still in their 30s, biologically speaking.
The study shows that our life experiences shape how we age by embedding themselves biologically and leaving a trace in our DNA through the process of methylation, which determines which genes are turned on and off. Evidence from mouse studies suggests that changes in the environment can alter methylation patterns, and this led the study team to explore if environmental factors such as stress or pollution might do the same for people.
“It’s still early days on the human studies, but several, including the Dunedin Study, have found that people who are ageing slower or faster, as tested by deterioration in blood test biomarkers, do look different on the amount of methylation on their DNA,” says Moffitt. “This occurs only at certain sites along the DNA, so it is now possible to check those sites to estimate if a person is ageing slow or fast.”
Among a host of early life experiences, mental disorders appear closely associated with an accelerated pace of ageing later in life. Another study, based on the health records of 1.7 million New Zealanders aged 21-60 when it began in 1988, followed them across three decades to test a link between mental disorders and an increased risk for subsequent dementia. It came as a surprise to the research team that mental disorders act as salient early-warning signs for later brain degeneration, more strongly linked with dementia than chronic physical diseases. The connection holds for men and women, for both early-onset and later-onset dementias and for different types of mental health conditions, and it cannot be explained by pre-existing chronic illness or social disadvantage.
The silver lining of such findings is that they deliver a strong argument for better and earlier support and treatment for people experiencing mental disorders in early life to lower the risk of cognitive decline later.
This applies more broadly to other aspects of ageing. The number of older New Zealanders has almost doubled in the past two decades. People aged 65 and older now make up 15% of the population, and the proportion is predicted to double again in the next 20 years. Pākehā New Zealanders at retirement age today can look forward to another two decades, but the life expectancy for Māori is seven years shorter.
If we heed the early-life warnings that contribute to faster ageing, there’s an opportunity to slow and delay the onset of several diseases and begin to address ageing inequity. It may not extend longevity, says Moffitt, “but what we can do is make those extra years more free from disease – a longer health span”.
We now know from the Dunedin Study how important a good childhood is for later life, she says. But that doesn’t mean faster ageing is inevitable for anyone who experiences traumatic events during childhood or struggles with mental illness. Having this knowledge in midlife may just act as a motivator to improve healthy eating, lift exercise levels and change health-damaging behaviours within our control.
Jellyfish Age Backwards: Nature’s secrets to longevity, by Nicklas Brendborg (Hodder Studio, $38).