In the early 1990s, Tom Perls met two people who would change his life. Perls, then a gerontology fellow at Harvard Medical School, was visiting Boston’s Hebrew Rehabilitation Center for Ageing and needed to see a couple of patients who just happened to be over 100. But he couldn’t find them in their rooms. He eventually tracked down one patient, a 103-year-old woman. She was busy playing Chopin and Mozart on the piano. Perls’ other patient, a 101-year-old former tailor, was discovered in the occupational health room mending his housemates’ clothes.
“They totally surprised me and that’s when the epiphany happened,” says Perls, who is now based at Boston University. “These folks seemed to be ageing incredibly slowly compared to other people.” He wanted to figure out their longevity secrets and vowed to find as many other centenarians as he could. The project became the New England Centenarian Study, the world’s largest study of exceptionally old people.
Centenarians are less rare than they used to be. In the UK, there were 15,120 centenarians alive in 2020 (almost double the figure in 2002), according to the Office for National Statistics. But becoming eligible for a birthday letter from the Queen is still a remarkable feat. We spoke to longevity experts about the science that might help all of us get there and the misconceptions about ageing you should stop believing.
To figure out how to slow (or even stop) ageing, we need to know why our bodies do it in the first place. But biologist Cathy Slack from Aston University, says scientists just aren’t sure yet. “From a purely theoretical perspective, there’s no beneficial reason to age,” she says. We used to think ageing resulted from a buildup of reactive oxygen species (free radicals) which caused molecular damage, but recent research suggests this is unlikely to be the full story. The current most popular explanation is that ageing is an unwanted side effect of biological processes that promote growth and reproduction in our younger years, says Slack.
After a certain point, the same mechanisms that once made us fitter start making us sicker and the body fails to turn them off. Scientists call this the ‘hyperfunction’ theory of ageing. “It’s like a tap being left on,” says Slack. “You need to fill the bath, but if you leave the tap on, the water overflows and you flood your bathroom.”
Findings from Perls’ study of centenarians showed the pianist and the tailor weren’t outliers. People who make it to 100 aren’t just long-living, they tend to avoid serious illness until the final chapter of their lives. His participants’ medical histories suggest there are three broad categories of centenarian. Around 43 percent are ‘delayers’ who don’t exhibit age-related diseases until they reach their eighties. Another 42 percent are ‘survivors’ who live with chronic disease from their 60s and 70s but it doesn’t kill them. The remaining 15 percent or so are ‘escapers’ - those with no clinically demonstrable disease at 100 years and over.
It’s true that age is a major risk factor for many serious illnesses such as heart disease, dementia and diabetes. But Perls believes the old adage ‘the older you get, the sicker you get’ is false. He prefers to think of it as ‘the older you get, the healthier you’ve been’.
It’s likely that centenarians, and especially super-centenarians (people who live to 110 and over) have genetic variants which protect them from age-related disease, says Perls. But genetics isn’t the full picture when it comes to longevity. In fact, research suggests only about 25 per cent of the variation in human lifespan is down to genes. Health-related behaviours and the environment make up the lion’s share.
Just look to California’s Seventh Day Adventists, says Perls. People from this Christian denomination tend to live up to a decade longer than the average Californian. They don’t smoke, drink, or eat meat, which might explain it. Perls thinks most of us could make it into our nineties simply by following a reasonably healthy lifestyle from middle age.
Nutritional epidemiologist Frank Hu, from Harvard TH Chan School of Public Health, agrees. His research, published in the British Medical Journal in 2020, uncovered five lifestyle factors that could gift you ten extra years of life. People who’d never smoked, didn’t drink much, had a normal BMI, exercised for around 30 minutes a day, and ate a high-quality diet expanded not only their lifespan but also the number of years they lived without serious diseases, such as diabetes, heart disease and cancer. The findings are cause for optimism, says Hu. “You don’t need to go vegan or run a marathon.” Small healthy tweaks might extend your life significantly.
Other longevity research zooms in on a type of cell that accumulates in our tissues as we get older. These cells no longer multiply, but they also refuse to die. Biologists once dismissed these zombies, called senescent cells, as irrelevant to health and disease. But some researchers now believe manipulating them could be key to better ageing. Biochemist Judith Campisi from the Buck Institute for Research on Aging in California found senescent cells ooze inflammatory proteins that damage tissue and halt surrounding cells from carrying out their normal processes. Removing them from the body might therefore slow down age-related decline.
In James Kirkland’s laboratory at Mayo Clinic, Minnesota, mice given drugs called senolytics, which selectively kill these senescent cells, survived for longer than normal and showed delayed onset of multiple conditions usually associated with ageing. Several biotech companies, such as Unity Biotechnology, have since set their sights on senolytics as a potential fountain of youth.
But not everyone is convinced. “I don't think they’re going to get a lot of people to 100,” cautions Perls. However, he does think senolytics might prove important for preserving health in later life. He’s currently investigating senescent cells in his centenarians (and their family members) to see if those who age incredibly well typically have a lower burden of the cellular undead.
Although studies of exceptionally old people are vital for helping us understand how to reverse ageing in humans, we’re also learning a lot about longevity from seemingly unrelated organisms such as worms and insects. “I often get an incredulous look when I say I work with fruit flies,” says Slack. “But what we recognise now is that animals across very diverse species actually age in quite similar ways.”
Slack’s research focuses specifically on insulin signalling and how it contributes to ageing. “What we know is this signalling pathway allows the animal to grow bigger and to reproduce when they’re young,” says Slack. But she’s found that if you inhibit this pathway, the laboratory creatures live far longer than they’re supposed to. Slack says she can extend the life of a fruit fly by up to 20 percent with no ill effects, other than the organism no longer being able to reproduce. Her work builds on a discovery from nearly 30 years ago when scientists removed the insulin-signalling receptor from a worm and doubled its lifespan. But more research is needed to determine whether such findings could be extrapolated to humans, and how you would manipulate vital signalling pathways without causing harm.
Scientists can help flies and worms live longer using genetic manipulation tools, but they also know an easier way of prolonging the lifespan of organisms: starvation. In the 1930s, biochemist Clive McCay discovered that rats with severely restricted diets lived up to 33 per cent longer than was previously thought possible. More recent research from the Salk Institute in California compared rats who had eaten 30 percent fewer calories than normal since middle age with animals on a standard diet. When the scientists analysed cells from multiple body tissues, they found cells from older dieting rats closely resembled those of much younger animals.
Such work raises the possibility that calorie restriction in humans would see similar gains in lifespan, and perhaps other health outcomes. But it’s not an attractive, or advisable, pursuit for most. Intermittent fasting diets (such as the 5:2) where people eat normally the majority of the time – save for a couple of days on a low-calorie diet – are popular for people trying to lose weight. And some experts believe these plans could have a longevity benefit, but the evidence is far from clear yet. “Some people find intermittent fasting is a great way to maintain a healthy weight,” says Slack. “But whether or not it’s going to be proven beneficial in terms of living longer is yet to be seen.”
It would be a whole lot simpler to just take a pill to prolong your life – and ideally, your health. Scientists have discovered some pharmaceuticals might do the trick. Immunosuppressant rapamycin appears to extend lifespan in mice. Likewise, diabetes drug metformin seems to help lab animals live longer. Even human studies of people taking the medication for type 2 diabetes have found metformin is associated with improved (unrelated) health outcomes such as fewer heart attacks and cancer diagnoses. And a 2014 study found those who took metformin (for diabetes) lived longer on average than matched non-diabetic patients who did not take the medication.
Such promising research has led to reports of people taking metformin off-label in the hope of a longer life. But there is still a lack of convincing clinical evidence that this medicine would be beneficial for healthy people. Researchers are intrigued though. In 2019, the FDA gave the green light to the Targeting Aging with Metformin (TAME) trial, led by Nir Barzilai, at the Albert Einstein College of Medicine in New York. TAME will explore whether metformin extends the number of years participants remain in good health (without stroke, heart failure, dementia, cancer or death). “It will be really exciting to see what happens,” says Slack. “Metformin is really cheap. And we need to be mindful that any kind of drug that’s going to improve ageing should be accessible to all.”
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This article was originally published by WIRED UK
