Tech entrepreneur Bryan Johnson is talking about 16th-century sailors. Back then, he says, circumnavigating the globe was the height of human achievement. But those sailors, some of whom were coincidentally hoping to find a mythical fountain of youth, left port without knowing what really lay ahead. The same is true for Johnson, 47, who sees himself as a modern-day explorer. Like those sailors, he too is pushing the bounds of what is humanly attainable. Not by circumnavigating the globe, but by circumventing death.
Johnson’s odyssey involves ingesting 111 pills a day, eating his last (vegan) meal of the day at 11am, staying teetotal, doing an hour of exercise daily and going to bed at 8.30pm. But is it scientifically possible to slow our ageing like this? Or is his plan more likely to end up shipwrecked by reality?
Living to even 100 is extremely difficult. In his recent book Jellyfish Age Backwards, the Danish molecular biologist Nicklas Brendborg estimated that it’s as hard to survive from 93 to 100 as it is to make it from birth to 93. And most would consider 93 a decent innings. “Your chance of being sick or dying increases exponentially with time,” says Prof Richard Faragher from Brighton University. Plentiful evidence suggests that a healthy lifestyle can add up to 14 years to our lives. But given UK life expectancy is about 81, this isn’t likely to make us centenarians. And a new study shows that the rise in life expectancy is slowing down.
But if we adopt extremely healthy lifestyles, might we live extremely long lives? Not really. Extreme longevity is seemingly more genetically driven than normal ageing, meaning diet and exercise may only have a limited impact, says Lynne Cox, an Oxford University professor. “I don’t think there’s a panacea that’s going to add 20 or 30 years to human life at the moment,” she says.
Take exercise – which clearly is good for us. One study of 55- to 79-year-old amateur cyclists found they were biologically young for their age. In particular, their immune systems hadn’t declined like their non-exercising peers. But that doesn’t mean we should do ever more exercise. Another recent study on Finnish twins, which has not yet been peer reviewed, found moderate exercisers were biologically younger than those who did no exercise – and, strikingly, those who did a lot.
“You really want to be in the sweet spot with exercise,” says Cox. “Super fit athletes don’t necessarily seem to be living any longer.”
As for diet, research shows that cutting calories can double the lifespan of nematode worms. Meanwhile, calorie-restricted mice can live about 30-40% longer, particularly if they do intermittent fasting. Results in rhesus monkeys have been contradictory, but calorie-restricted monkeys appear healthier and may live a couple of extra years. Johnson, who is restricting his calories by 10%, is hoping it will work for him, too. But the restrictions in the animal studies are large (a 30-40% reduction in calories) and humans aren’t mice – or nematode worms.
While a few studies show health benefits for humans, it’s difficult to verify that participants really maintained the restricted diets. Plus, says Cox, “it’s very, very hard to not become malnourished if you’re cutting out 30% of your calories. It can actually be detrimental.” This is particularly true if you’re older, losing muscle mass, or restricting your calories indefinitely. Research shows older, calorie-restricted mice are at a higher risk of dying from infections.
Weight-loss jabs such as Ozempic are also popular among longevity enthusiasts – though Johnson says he hasn’t tried it. New research shows they cut the risk of many age-related diseases, including cardiovascular diseases and cancer, leaving researchers optimistic they could extend life. But we won’t know their impact on lifespan for decades. They also come with potentially life-threatening side-effects, including pancreatitis. It’s also worth noting that skinny people don’t seem to live the longest. Strikingly, overweight people live longer than their underweight, normal and obese peers.
The mystery of centenarians
Some people do enjoy very long lives. The world’s “blue zones” (regions identified as having populations who live healthier and longer lives than others) – which include Sardinia in Italy, Okinawa in Japan and Ikaria in Greece – have spawned an industry of lifestyle interventions, supplements and cookbooks. But a study by Saul Newman from University College London, which is now being peer reviewed, suggests much data on human centenarians is bogus.
“I tracked down 80% of the people in the world who were older than 110,” says Newman, who found almost none of them had a birth certificate. “It’s a statistical garbage pile.”
Alarm bells have been ringing for a while. In 2010, a Japanese government review discovered 230,000 of the country’s centenarians were missing – presumably dead. And Newman says data suggests that some 72% of Greek centenarians are dead or missing, but their relatives haven’t declared as much, possibly to keep collecting their pensions.
Newman believes this is why blue zones appear in poor, rural areas, places where there’s substandard record-keeping and pressure to commit pension fraud. In the UK, the relatively poor London borough of Tower Hamlets has the highest proportion of 105-year-olds in the country, despite having a lower-than-average life expectancy overall. And longevity is linked to wealth – the countries in the world with the highest average life expectancy are rich ones.
“The old-age suicide rate in Okinawa is the fourth highest in Japan. They have twice the poverty rate of any other prefect. They’re last in Japan for vegetable consumption,” says Newman. “If you pretend that everything’s great in Okinawa, you are leaving those people behind – you’re exploiting them to sell cookbooks.”
“He’s right,” says Nir Barzilai, a longevity researcher at the Albert Einstein College of Medicine, who has studied Ashkenazi Jewish centenarians in the US and their families. “It’s a real problem.” However, he argues records are fairly reliable in the US. And his team looks at many different documents, including passports, voting records and the ages of family members, to verify their centenarians.
His own results do differ from those based on blue zones. Barzilai’s centenarians didn’t have very healthy lifestyles, for example. “Half of them were overweight or obese, half of them were smoking, half of them weren’t exercising, and very few were vegetarians,” he says. But they were healthy – having only half the incidence of cardiovasular disease.
“They have genes that slow their ageing,” explains Barzilai, who’s working on identifying them. He’s already discovered some 60% have genes that lower their levels of growth hormones in late life. This all suggests that genes, rather than lifestyle, are the secret to becoming a centenarian.
Cellular ageing
Not all species age like humans. Take ocean quahogs (a species of mollusc), rockfish and Greenland sharks, which don’t have an exponentially increased death rate with age. “Our knowledge of the mechanisms of ageing is incomplete,” says Faragher.
A key driver of ageing is a process called cell senescence. Cells enter this toxic state as we age, damaging tissue and generating inflammation and disease. But Cox and colleagues have shown that you can slow ageing if you manipulate these cells to behave as if they were younger. In 2009, a hugely promising study showed the drug rapamycin could make mice live up to 14% longer. A clinical trial on humans has even shown that when elderly people were given a low dose of a rapamycin-like drug for eight weeks, it boosted their immune system, and led to a 50% reduction in infections for a year.
Other promising, FDA-approved drugs that can extend the lifespan of animals and lead to greater health and reduced mortality in humans include diabetes medicines such as metformin, canagliflozin and dapagliflozin. Barzilai, however, stresses that these drugs have only been shown to work in people over 50. If you’re young, or you combine several of these drugs, you may find they cause harm such as reduced muscle mass and testosterone. Similarly, rapamycin can “trigger diabetes, ulcers and prevent wound healing at high doses”, says Cox.
Johnson, who takes rapamycin and metformin, acknowledges this. “Metformin has so many effects on the body”, he says. “It may have some kind of effect on muscle to some degree, but it may have a whole bunch of positive effects too.”
Another option is to deal with senescent cells by deleting them. Compounds found in many fruits and vegetables, including dasatinib, navitoclax, quercetin and fisetin, have shown promise in deleting such cells – and are now sold as supplements. Such drugs may also treat diabetic kidney disease and idiopathic pulmonary fibrosis in humans, both caused in part by senescent cells.
Faragher has also shown that resveratrol, found in grapes, can reverse cell senescence. But again, senescent cells do some good, too, such as healing wounds, which means it can be risky getting rid of them. We don’t know for sure whether these drugs or supplements will actually help humans live considerably longer. But many longevity enthusiasts including Johnson are already taking them. Faragher, however, doesn’t believe any of this will lead to an “immortality pill”. Rather, these kinds of drugs could be “a bit like antibiotics” – taken during a limited time when you’re ill or ahead of vaccination to enhance the immune system.
More experimental techniques exist, but may cause cancer. These include “epigenetic reprogramming” of cells to make them younger and gene therapies aimed at lengthening our telomeres – protective caps on chromosomes that shorten with age. But while short telomeres are linked to a short lifespan, long telomeres boost cancer risk.
“I’m very hesitant about the telomerase stuff because of the cancer risk, though some newer studies suggest it’s possible to minimise that risk,” says Cox.
So where does that leave us? Unfortunately, it appears to be a waiting game. Despite genuinely promising research, a lack of human trials means there’s still no proven way to live significantly past 100. Researchers also warn against mixing and matching drugs and interventions the way Johnson does. “Each one might buy a little bit of extra time. But if you put them all together, you might do worse rather than better,” says Cox.
But Johnson is optimistic. “I’ve arguably got the best biomarkers in the world,” he says, adding that scientists, who “are spending 75% of their time writing grant proposals”, should learn to value the open source data he provides – especially as other people are copying his protocol.
Barzilai disagrees, stressing that one self-experimenting individual does not constitute a scientific study. “If Bryan Johnson dies, which I think is possible because he is doing a lot of crazy things together, it will reflect badly on us.”
