TI entrepreneur Bryan Johnson talks about 16th century sailors. Back then, he says, circumnavigating the globe was the pinnacle of human achievement. But those sailors, some of whom happened to be hoping to find a mythical fountain of youth, left port without knowing what really lay ahead. The same applies to Johnson47, who considers himself a modern-day explorer. Like those sailors, he also pushes the boundaries of what is humanly achievable. Not by circling the globe, but by circling death.
Johnson’s odyssey involves intake 111 pills a day, ate his last (vegan) meal of the day at 11:00, stayed teetotal, exercised for an hour daily and went to bed at 8:30 p.m. But is it scientifically possible to slow down our aging like that? Or is it more likely that his plan is shipwrecked by reality?
Living to even 100 is extremely difficult. In his recent book Jellyfish Age BackwardsDanish molecular biologist Nicklas Brendborg estimated that it is as difficult 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. Abundant evidence suggests that a healthy lifestyle can add up to 14 years to our lives. But as UK life expectancy is around 81, that probably won’t make us centenarians. And a new study shows that the increase in life expectancy is slowing down.
But if we assume extremely healthy lifestyle, may we live extremely long lives? Not really. Extreme longevity appears to be more genetically driven than normal aging, meaning that diet and exercise may have only a limited impact, says Lynne Cox, a professor at the University of Oxford. “I don’t think there’s a panacea that’s going to add 20 or 30 years to human life right now,” she says.
Take exercise – which is clearly good for us. One study of 55- to 79-year-old amateur cyclists found them to be biologically young for their age. In particular, their immune systems did not decline like their non-exercising counterparts. But that doesn’t mean we still need to do more exercise. Another recent study on Finnish twins, which has not yet been peer-reviewed, found that moderate exercisers were biologically younger than those who did no exercise—and, strikingly, those who did a lot.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. “It doesn’t seem like super fit athletes necessarily live longer.”
When it comes to diet, research shows that cutting calories can double the lifespan of nematodes. Meanwhile, calorie-restricted mice in particular can live about 30-40% longer if they are intermittent fasting. Results in rhesus monkeys have been conflicting, but calorie-restricted monkeys appear to be healthier and may live a few extra years. Johnson, who restricts his calories by 10%, hopes it will work for him too. But the limitations in the animal studies are great (a 30-40% reduction in calories) and humans are not mice – or nematode worms.
While some studies shows health benefits for humans, it is difficult to verify that participants actually maintained the restricted diet. Plus, says Cox, “it’s very, very hard not to become malnourished when you cut 30% of your calories. It can actually be detrimental.” This is especially true if you are older, losing muscle mass or restricting your calories indefinitely. Research shows older, calorie-restricted mice have a higher risk of dying from infections.
Weight-loss punches like Ozempic are also popular with longevity enthusiasts — though Johnson says he hasn’t tried them. New research shows that they reduce the risk of many age-related diseases, including cardiovascular disease and cancer, leave researchers optimistic they can prolong life. But we won’t know its impact on lifespan for decades. They also come with potentially life-threatening side effects, including pancreatitis. It’s also worth noting that thin people don’t seem to live the longest. Striking, overweight people live longer than their underweight, normal and obese peers.
The mystery of centenarians
Some people enjoy very long lives. The world’s “blue zones” (regions identified as having populations that live healthier and live longer than others) – which include Sardinia in Italy, Okinawa in Japan and Ikaria in Greece – an industry has sprung up of lifestyle interventions, supplements and cookbooks. But a study by Saul Newman of University College London, now being peer-reviewed, suggests that much of the data on human centenarians is bogus.
“I tracked down 80% of the people in the world who were over 110,” says Newman, who found almost none of them had a birth certificate. “It’s a statistical dump.”
Alarm bells have been ringing for a while. In 2010, a Japanese government review discovers 230,000 of the country’s centenarians are missing – presumed dead. And Newman says data suggests that about 72% of Greek centenarians are dead or missing, but their relatives have not declared as many, possibly to continue collecting their pensions.
Newman believes this is why blue zones occur in poor, rural areas, places where there is substandard record-keeping and pressure to commit pension fraud. In the United Kingdom, the relatively poor London borough of Tower Hamlets has the highest percentage of 105-year-olds in the country, despite 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 countries.
“The elderly suicide rate in Okinawa is the fourth highest in Japan. They have twice the poverty rate of any other prefect. They are last in Japan for vegetable consumption,” says Newman. “If you pretend that everything is great in Okinawa, you’re leaving those people behind – you’re exploiting them to sell cookbooks.”
“He’s right,” said 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 a very healthy lifestylefor example. “Half of them were overweight or obese, half of them smoked, half of them didn’t exercise, and very few were vegetarians,” he says. But they were healthy – with just half the incidence of cardiovascular disease.
“They have genes that slow down their aging,” explains Barzilai, who is working to identify them. He has already discovered that about 60% have genes that lower their levels of growth hormones in late life. All this suggests that genes, rather than lifestyle, are the secret to becoming a centenarian.
Cellular aging
Not all species age like humans. Take sea brush (a species of mollusk), rockfish and Greenland sharkswhich does not have an exponentially increased death rate with age. “Our knowledge of the mechanisms of aging is incomplete,” says Faragher.
A key driver of aging is a process called cellular senescence. Cells enter this toxic state as we age, damaging tissue and causing inflammation and disease. But Cox and colleagues showed that you can slow down aging if you manipulate these cells to act like they are younger. In 2009, s extremely promising study showed that the drug rapamycin could make mice live up to 14% longer. A human clinical trial even showed that when elderly people were given a low dose of a rapamycin-like drug for eight weeks, it strengthen their immune systemand resulted in a 50% reduction in infections for a year.
Other promising FDA-approved drugs that may extend lifespan in animals and lead to greater health and reduced mortality in humans include diabetes drugs such as metformin, canagliflozin and dapagliflozin. However, Barzilai emphasizes that these drugs have only been shown to work in people over 50. If you are young, or you combine several of these drugs, you may find that they cause harm such as reduced muscle mass and testosterone. Similarly, rapamycin “can cause diabetes, ulcers, and prevent wound healing at high doses,” says Cox.
Johnson, who takes rapamycin and metformin, admits this. “Metformin has so many effects on the body,” he says. “It can have some kind of effect on muscle to some extent, but it can also have a whole lot of positive effects.”
Another option is to deal with obsolete cells by deleting them. Compounds found in many fruits and vegetables, including dasatinib, navitoclax, quercetin and fisetinhave shown promise in eradicating such cells – and are now sold as supplements. Such drugs can also treat diabetic kidney disease and idiopathic pulmonary fibrosis in humans, both caused in part by senescent cells.
Faragher also showed that resveratrol, found in grapes, can reverse cell aging. But then again, aged cells also do some good, like healing wounds, which means getting rid of them can be risky. We don’t know for sure if these drugs or supplements will actually help people live significantly longer. But many longevity enthusiasts, including Johnson, already take them. However, Faragher does not believe any of this will lead to an “immortality pill”. Rather, these types of drugs can be “a bit like antibiotics” – taken during a limited time when you are sick or before vaccination to boost the immune system.
More experimental techniques exist but can 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 increase cancer risk.
“I’m very hesitant about the telomerase stuff because of the cancer risk, although some newer studies suggest that it might be possible to reduce that risk,” Cox says.
So where does that leave us? Unfortunately, it seems to be a waiting game. Despite really promising research, a lack of human trials means there are still none proof way to live well past 100. Researchers also caution against mixing and matching drugs and interventions as Johnson does. “Everyone can buy a little extra time. But if you put them all together, you might do worse than better,” says Cox.
But Johnson is optimistic. “I probably have the best biomarkers in the world,” he says, adding that scientists, who “spend 75% of their time writing grant proposals,” should learn to value the open-source data he provides — especially as other people copy its protocol.
Barzilai disagrees and emphasizes that one self-experimenting individual does not constitute a scientific study. “If Bryan Johnson dies, which I think is possible because he does a lot of crazy things together, it will reflect badly on us.”
