“It’s time to classify biological aging as a disease.”

To the uninitiated, this may sound like self-optimization gobbledygook. But in a particular segment of the biology world, known as the longevity (a.k.a. the life-extension, or anti-aging) community, the call to reclassify aging as a disease has become a serious undertaking. Over the past two and a half decades, proponents have advanced this cause from the fringes of scientific discourse to the highest offices of biopolitical power. In 2019, for example, the World Health Organization seriously considered including aging in its authoritative International Classification of Diseases. What exactly is being pushed for here, and why?

A standout version of the underlying argument was published by four biologists in 2015. Their argument went as follows: What we as a society consider a disease, and what we consider normal, is historically myopic. Drapetomania, masturbation and homosexuality were all considered diseases not too long ago, while osteoporosis and Alzheimer’s were considered as normal and natural as life itself.

Having softened our rigid world of definitions, the four co-authors—Sven Bulterijs, Raphaella Hull, Victor Björk, and Avi Roy—made the case for a fundamental reshuffling. They took aim at the idea that physiological aging serves some kind of natural purpose. Far from reflecting evolutionary intent, aging in their view is a result of evolutionary neglect. Accepting this undesirable decline as a necessary outcome, they argued, is defeatist and indeed deadly. It not only stands squarely in the way of developing new anti-aging treatments; it could prevent possibly harmful medicines from being regulated sufficiently. Declaring biological aging a disease would loosen up the resources, and bulk up the infrastructure, necessary for defeating the most prolific killer of all.

By the time their paper was published in 2015, biologists had managed to extend the lives of roundworms ten times over; and doubled the lifespans of flies and mice. The foray into human anti-aging experiments, still in its infancy then, has since escalated dramatically. The WHO ultimately decided in 2018 against re-classifying aging as a disease—a panel of experts decided such a move might exacerbate ageism—but the idea behind the call has only picked up steam. The driving force behind it is greater than a new multi-billion dollar market. It comes from a shift in our scientific understanding of life’s most fundamental metric—and possibly, the uncoupling of biological and chronological age.

Disputed Fundamentals

What is aging? Over the past couple decades, an explosion of research has painted an intricate picture of this shadowy process at the level of our cells. DNA accumulates damage like rust; proteins and enzymes dysfunction and become out of balance; stores of youthful cells dry up, and cranky old ones overstay their welcome. Together, they contribute to our progressive dwindling, drawing us ever closer to that perfect darkness.

Scientists working in this field hope that these findings may soon help us determine the biological origins of aging. They have taken to studying centenarians, elephants, short-lived fish, and surprisingly old rodents in search of that uniform factor. The dominant theory emerging from this research posits that chemical hitchhikers on DNA, called epigenetic changes, control our aging process. Proponents of so-called Epigenetic Aging say they can read these changes at any given moment like a "clock," and calculate the biological age of almost any mammal.

"Some species fly like bats, other species are in the ground. [You’d think] they would accumulate damage in very different ways. However, what we have shown are these amazing commonalities," says Steve Horvath, a biostatistician. The fact that so many species share a process of aging suggests something about evolution; Horvath is on a mission to find out what that is. Based on genetic data from dozens of species, he and his colleagues have developed a single mathematical formula to measure age in hundreds of tissues and species. This formula can estimate age from methylation—the chemical process behind epigenetic change—for all mammalian species, simply by accounting for their intrinsic biology, like age at sexual maturity, gestation time, and lifespan. "One formula, that's it. The minute you have a mathematical formula, you start to think there's a law."

According to more practically minded scientists, if we understand the true biological reasons for age, then we can invent technology to stop or slow it. And if aging turns out to be preventable, regardless of definition, we will already be one step closer to treating it like an illness.

Clockwatchers

But if aging is a disease, how does it work exactly? When researchers probe for epigenetic age, they’re looking for chemical interlopers along stretches of DNA. They call these methylation patterns, after branches of “methyl” groups, which (like methane) contain a single carbon atom. Those sticky carbons make a world of difference. They control gene expression—meaning that their presence or absence influences how your cells function. Methylation may be the villain that withers us.

Where an organism’s genetics are a static, lifelong blueprint for cells, its epigenetics are more dynamic. “I almost think of it as the operating system of the cell,” says Morgan Levine, a principal investigator with Altos Labs, adjunct professor at Yale, and expert on the epigenetics of aging. Methylation tells cells what to do: proliferate, differentiate, whatever. “You'll have the same genotype when you're 20 and when you're 70. But we know your risk of developing heart disease, or Alzheimer's is not the same when you're 20 and 70.” Levine thinks epigenetics account for those changes.

DNA methylation correlates with aging in humans and evolves predictably with time. Diseases associated with aging, like heart failure, early-aging disorders, and neurological dysfunction appear as “accelerated” methylation, given a person’s chronological age. “No one has really shown whether they're causal,” Levine told me, but the statistical measure has since become a weapon of choice for research labs that experiment with anti-aging interventions.

Methylation also tracks with mortality. In 2016, an international team of scientists found that epigenetic clocks can predict death in a population better than chronological age. In 2021, Finnish researchers tracked the natural epigenetic changes in pairs of twins. They supposed that differences between each twin’s lifestyle might appear as “accelerated aging” in their epigenetic fingerprint. They found that one type of epigenetic clock called GrimAge predicted mortality more reliably than any genetic correlations.

Consumers are already being sold methylation clocks, which ostensibly tell a person their true cellular age and so invite them to slow the hands of time by changing their life choices. These clocks offer a new metric that may tell us more about the quality of life, and the probability of death, than the number of candles on your birthday cake.

Methylation clocks are becoming a hot commodity in a new thriving subculture of anti-aging enthusiasts that gather in forums like Reddit’s r/Longevity. This is where Holly Mann, an internet marketer, found MyDNAge. She remembers awaiting the results nervously. “My heart started racing a little. I said a little prayer like, ‘Please God, don’t let it be bad,’” she recalls in a vlog recorded for her YouTube followers. She was 37 when she took the test. The report said her biological age was 34. She felt emboldened to continue experimenting, hoping that the next time she took the test, her “age” might fall to 32.

In this new subculture, epigenetic clocks are treated like fitness trackers. They offer more than a diagnosis; they present a challenge. For users, this idea from the future—my body is younger than me—already seems a reality.

Philosophical Obstacles

The question of whether to treat aging as preventable divides people along multiple lines. Those least familiar with the biological “rules” suffer no limits to their imagination. Endless rejuvenation? Freezing aging? Practical immortality? Sure, why not. Those who are more acquainted with science—and perhaps hold PhDs in physics or biology—are trained skeptics when ideas seem this fantastical. Ironically, researchers working on the bleeding edge of anti-aging technologies are closer to the civilians in their appreciation for how quickly things can change. This starry-eyed quality has served them well. The perception of the field has shifted dramatically over the past decade.

Biology and technology companies (and the marriage of the two, biotech companies) are throwing billions of dollars at life extension technologies. They want to invent techniques that rejuvenate our cells and test drugs that may slow or reverse aging. The average lifespan (about 73, globally) has room to grow simply by treating age-associated conditions, like diabetes and Alzheimer’s. We may see more humans live past their 120s, the current maximum lifespan. Boosters of this research believe that the main obstacles to these breakthroughs are political and philosophical.

And indeed there are reasonable concerns that prolonging the life of a person would be bad news for people. Overpopulation strains access to finite resources. Economists traditionally consider an aging population a natural inhibitor of economic growth, as fewer people pay into the tax base. The UN estimates that 22% of the population will be over 60 in 2050, up from 8% in 1950. Scientists working in the anti-aging sector have a ready retort to this. Slowing the effects of aging, they argue, would mean that older people would be able to work happily and healthily for longer, stopping them from becoming economic dependents. But how would a new world of overactive centenarians change our value system, our sense of what matters?

If the aging is a disease-crowd draws a lot of outrage, this is because they are going up against almost everything that came before. The eminent bioethicist Leon Kass famously argued that mortality keeps life interesting. Would it thus be boring to live longer, or to live without a deadline? Does more life just mean more suffering? Schopenhauer wrote that the brevity of life “so often lamented, may perhaps be the very best thing about it.”

Ingemar Patrick Linden, a leading philosopher of the longevity community, naturally disagrees. He likens Schopenhauer’s view to “an insane supervillain in a Marvel Universe.”  Linden considers himself a “death abolitionist.” He is quick to note that this attitude remains somewhat fringe (though to an enterprising philosopher, that’s something of a perk). But in Linden’s estimation, seeing life as a net hardship that needs to come to an end is “akin to arguing that one of the good things about getting diabetes and necrotic limbs is that it makes it easier to accept having one’s limbs amputated.” In his landmark work The Case Against Death, Linden cites economic arguments for extending life as far as possible. The economists he cites estimate that extending the American lifespan by one year is worth $38 trillion. Extending life spans by ten years would be worth $367 trillion.

These calculations, however, do not account for the cost of possible side effects of these speculative technologies, such as a new wave of some unforeseen cancer. That makes the fact that they’re disproportionally being pursued by private companies, rather than government-funded research, a worrisome arrangement. On the other hand, the current slate of recommendations for how to prolong human life are nothing if not benign. Above all, methylation clock-watchers recommend improving one’s diet, exercising regularly, and not smoking.

Linden, however, insists on a grander vision. The acceptance of aging and death is contrary to liberty itself. “It’s the ultimate unfreedom,” he tells me. In his view, this new wave of biology, chemistry, and now philosophy is a bold attempt to finally take control over the ultimate contingency. He seems optimistic that public attitudes will change as the technology becomes less speculative. Against all odds, he seems to say, we will choose life. ♦