Wednesday, October 19, 2022

The debate over whether aging is a disease rages on

The debate over whether aging is a disease rages on

The debate over whether aging is a disease rages on https://ift.tt/b6uYThI

Last year, over Canadian Thanksgiving weekend, Kiran Rabheru eagerly joined a call with officials from the World Health Organization (WHO). Word had spread of a change coming to the WHO’s International Classification of Diseases (ICD), a catalogue used to standardize disease diagnosis worldwide.

In an upcoming revision, the plan was to replace the diagnosis of “senility,” a term considered outdated, with something more expansive: “old age.” The new phrasing would be filed under a diagnostic category containing “symptoms, signs, or clinical findings.” Crucially, the code associated with the diagnosis—a designation that is needed to register new drugs and therapies—included the word “pathological,” which could have been interpreted as suggesting that old age is a disease in itself. 

Some researchers looked forward to the revision, seeing it as part of the path toward creating and distributing anti-­aging therapies. But Rabheru, a professor at the University of Ottawa and a geriatric psychiatrist at the Ottawa Hospital, feared that these changes would only further ageism. If age alone were presumed to be a disease, that could lead to inadequate care from physicians, he says. Rather than pinpoint exactly what’s troubling a patient, a problem could simply be dismissed as a consequence of advanced years. 

“The crux of the matter is that if you legitimize old age as a diagnosis, you run the risk of a lot of people using it inappropriately,” Rabheru says. A number of experts agreed. “There was a huge momentum that built up globally to say, ‘This is wrong,’” he says. 

Rabheru became part of a group that secured the call with the catalogue team. Those on his side presented their arguments and, he says, were “very pleasantly surprised” by the response—a formal review followed by a retraction. On January 1, 2022, the 11th version of the ICD was released without the term “old age”—or language that suggests aging is a disease—in its contents.

The decision wasn’t welcomed by everyone. “The exciting move by the @WHO to define AGING as a treatable MEDICAL CONDITION has, sadly, reverted,” tweeted David Sinclair, a professor at Harvard Medical School and an influential and sometimes controversial force in the study of aging thanks to his bold claims

“My question to the scientists and doctors who protested the inclusion of old age in their handbook is: What is so threatening?” Sinclair says. “I would really love to know the motivation, besides just trying to maintain the status quo.” 

Sinclair is also concerned about ageism. But he argues that the best way to combat ageism is to tackle aging: facing the problem head-on by devising treatments to slow its progress. “The current view that aging is acceptable is ageism in itself,” he says.  

In the years leading up to the debut of ICD-11, a number of researchers argued that linking old age more directly to disease would help the field of longevity research overcome regulatory obstacles, paving the way for drugs designed specifically to treat aging. 

This issue, however, is seemingly becoming less of a concern as anti-­aging research becomes more mainstream. The US Food and Drug Administration, for example, has said it doesn’t consider aging a disease. But in 2015, the agency made the surprising decision to greenlight the Targeting Aging with Metformin (TAME) study, a clinical trial that aims to show that aging can be targeted head-on, by testing whether the diabetes drug metformin can delay the development or progression of chronic diseases associated with aging.

Sinclair sees the WHO’s decision as a temporary setback. “Fortunately, the momentum is there from scientists, from the public, from investors,” he says. “This is going to happen, and changes to some of the language in a document aren’t going to stop progress.”

Even so, he says he would have liked to have the WHO’s endorsement of the notion of aging as a disease: “Language is extremely important to how society views problems and potential solutions.” 

This back-and-forth may seem like an issue of semantics. But the debate over the ICD’s language cuts to the heart of ongoing conversations about aging and whether a biological process that contributes to the risk of developing a number of diseases is itself a disease.

Even longtime researchers struggle with the definition of aging, says Simon Melov, a professor at the Buck Institute for Research on Aging. Melov, whose lab examines the core mechanisms that drive aging, thinks of it as “a decline of function with time.”

Taken a step further, from a biological standpoint, aging can be thought of as an accumulation of molecular changes that eventually undermine the integrity and resiliency of the body. Daniel Belsky, an assistant professor at the Columbia Mailman School of Public Health, views aging from this perspective: “Aging is a cause of disease, not a disease itself,” he says.

Some researchers say it does not make sense to frame something that is a normal biological process as disease. Further complicating things, Belsky says, is that there is no agreed-upon point at which a person becomes old. People of the same age can have strikingly different biological ages, based on observed changes like cell deterioration. 

Others assert that if a condition is treatable, it is a disease. This can be a confusing argument: there are diseases that aren’t treatable and “treatments” for things we might not necessarily classify as diseases. But if the argument holds, even if there is no treatment for aging right now, perhaps it’s enough if it’s conceivable there could be one in the future.

Aging isn’t entirely gone from the ICD-11. There’s still an extension code for “aging-related” diseases, but rather than being defined as those “caused by pathological process,” they are now said to be “caused by biological process.” Meanwhile, instead of old age, the catalogue uses the term “aging-associated decline in an intrinsic capacity” as a diagnostic description. 

“Everything is within reach.”

Ming Guo, director of UCLA’s Aging Center
Dr Ming Guo

Ming Guo, the director of UCLA’s Aging Center, likes this revision for its accuracy—and its potential. “It acknowledges aging and offers the opportunity to think there are things we can improve,” says Guo, who is researching aging reversal strategies. “It implies we can change our fate to a certain extent.” 

Work is moving forward regardless. Silicon Valley, which has a long history of investing in anti-aging research, has a new batch of longevity-related startups like Turn Biotechnologies and Altos Labs. Saudi Arabia plans to invest $1 billion a year in research to extend health span, the number of years a person remains healthy. Meanwhile, the US National Institutes of Health is actively asking scientists to apply for funding for age-related research. When asked about the ICD change, Luigi Ferrucci, scientific director of the National Institute on Aging, said it was “a good choice” because it supports the idea that “aging has functional consequences.”   

“Research, along with the budget, has been steadily increasing over the last 20 years,” Melov says. “It’s not a lack of money or a semantic thing of aging as a disease or not a disease that’s holding the field back.”

Rather, what the field needs to move forward, Melov says, are investigators who ask “sharp, hard questions” and can investigate topics when the tech they need is still in development. 

He is excited about rapid advances in technologies, like microscopy and single-­cell sequencing, that are enabling scientists to get new insights into aging at a cellular level. There will likely be major breakthroughs in animal models over the next two to five years, he says. But he still questions whether we’ll ever have an anti-aging therapeutic as effective as diet and exercise. “Even if we did have a therapeutic which, let’s say, was 50% as beneficial as a good diet and exercise—and that would be a very successful drug—it’s still going to have side effects,” Melov says. “So would you rather exercise three times a week and eat well or take that pill?” 

Belsky sees other low-hanging fruit. “If we want to slow aging, then it would be good if we all got to drink clean water and breathe clean air,” he says. “That’s a first step where we could actually make a lot of progress.”

Others still see great potential in the lab. Guo likes to say she wants to reverse the aging process, but her primary focus is on staving off age-related diseases to extend the human health span. She says when she first started talking to people about her plans five years ago, they didn’t believe it was possible to halt—let alone roll back—the effects of aging. But her team had already shown it could remove up to 95% of damaged mitochondria in fruit flies. The organelles become dysfunctional with age, which may increase an individual’s susceptibility to age-related diseases. 

“This is not science fiction,” Guo says. “Everything is within reach.”

Sarah Sloat is a journalist based in Brooklyn, New York.

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