Manu Joseph: There’s crushing news for people who want to live long

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A few days ago, Bryan Johnson, a centi-millionaire who has spent millions on reversing ageing—especially his own—posted some bad news for humanity on his YouTube channel. Rapamycin, which for a long time has been the most promising molecule in our quest to prolong youth, was not making him younger; instead, it was “accelerating” his ageing.

Johnson, who is 47 and looks 46, conducts various experiments on himself in his effort to live like a young man for a very long time. I am counting on him. His food consumption is so calibrated that he knows the number of calories he has gulped. He does not eat after 11am, unless he has to meet people socially and must eat at ungodly hours like 7pm just to shut them up. He sleeps around 8:30pm, alone. 

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I know he has high standards for himself because he recently visited Delhi, probably out of ignorance, and refused to breathe the air for too long. Among the most important things he was performing on himself was taking small quantities of rapamycin, a drug that is chiefly used to prevent the body’s rejection of organ transplants. It does not have approval as an anti-ageing drug, though it is widely believed to have potential for that. The compound had extended the lifespan of mice and worms beyond ambiguity, and of other animals, too. Johnson was its most famous human test subject.

Rapamycin was probably the world’s best shot at achieving prolonged youth by just popping a pill. It still is, because science will persist. But Johnson’s verdict is a crushing blow. In September, he stopped taking it because of signs that it was harming him. In January, he wrote, “Despite the immense potential from pre-clinical trials, my team and I came to the conclusion that the benefits of lifelong dosing of Rapamycin do not justify the hefty side-effects (intermittent skin/soft tissue infections, lipid abnormalities, glucose elevations, and increased resting heart rate).” 

Also, the way his body was reacting to the drug nudged him to take seriously a recent research paper that said the compound may accelerate ageing across 16 biological markers of age. A few days ago, he made a video to announce the bad news.

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The moment he went public, in a logical world, ministers would have rushed into huddles to ask “what now?” and our phones would be abuzz with “did you hear?” and billionaires would’ve cleared their schedules to deal with the sorrow that the probability of their mortality was higher than they had hoped. But, strangely, this is not how humans react to news that there is a good chance a miracle drug is not one.

Like many startling drugs, rapamycin was discovered accidentally. In the 1960s, a group of scientists collected soil from a remote island in the southeastern Pacific Ocean, Rapa Nui, also known as Easter Island. One of the scientists, Suren Sehgal, found that the soil sample contained a powerful anti-fungal agent produced by a soil bacterium. He grew a culture of it, and either he or his company Ayerst named it rapamycin after Rapa Nui. 

Soon scientists realized it was much more than an anti-fungal agent. “It was a potent immunosuppressant and stopped cells from multiplying,” writes Venki Ramakrishnan in his book Why We Die: The New Science of Ageing and Longevity. (An immunosuppressant drug impedes the body’s immune system from mistakenly attacking its own tissues.)

There’s a protein mechanism in our cells that controls how they behave. When nutrients are plentiful, cells grow, multiply and store fat. But when they are scarce, cells slow down growth and fat storage, and instead focus on cleaning up damaged parts and recycling them. All living things have this, which means that evolution thought it was very important.

Rapamycin can mimic this nutrient-deficient state, prompting cells to shift into maintenance and repair mode. For some reason, when cells do this, it extends the organism’s lifespan. This is why fasts are believed to be beneficial. Rapamycin essentially mimics fasting conditions.

A strange thing about food is that it supports life but also eventually kills. Its excess, chiefly, affects us at a cellular level. People who are slightly deficient in food tend to be healthier than the gluttons. A miracle I know from close observations of Malayalee alcoholics who eat moderately is that they outlive food addicts. Rapamycin can make the cells of gluttons think they are starved.

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Rapamycin’s key ingredient is only found on that remote Pacific island. Peter Attia says in Outlive, “It was uncanny: this exotic molecule, found only on an isolated scrap of land in the middle of the ocean, acts almost like a switch that inhibits a very specific cellular mechanism that exists in nearly everything that lives. It was a perfect fit, and this fact still blows my mind every time I think about it.” But Rapamycin does not seem to work as well in humans as it does in some animals. Nobody is sure why.

You may wonder what the fuss is about. Some humans already have lived way beyond 100; we just need to study them. Some centenarians are said to have lived heartily on wine and tasty breads. Haven’t we all heard of the Mediterranean people and those in Okinawa? Sadly, most of these stories are erroneous or exaggerated.

Saul Newman, a researcher, wrote in The New York Times that there has been a significant drop in claims of people living over the age of 110 since the advent of birth certificates. Most claims of advanced age could be clerical errors and frauds. This holds true for Okinawan and Mediterranean tales of long life. We needed Rapamycin to work.

The author is a journalist, novelist, and the creator of the Netflix series, ‘Decoupled’.