New approaches to the biology of #senescence can make lives longer and healthier.
LIFE EXPECTANCY IN the best-performing countries has been increasing by three months per year every year since the early 1800s. Throughout most of human history, you had a roughly 50–50 chance of making it into your twenties, mainly due to deaths from infectious diseases and accidents. Thanks to medical advances, we’ve gradually found ways to avoid and treat such causes of death; the end result is perhaps humanity’s greatest ever achievement—we’ve literally doubled what it means to be human, increasing lifespans from 40 to 80 years. On the other hand, this has allowed one scourge to rise above all the others to become the world’s largest cause of death: aging.
Aging is now responsible for over two-thirds of deaths globally—more than 100,000 people every day. This is because, counterintuitive though it may sound, the chief risk factor for most of the modern world’s leading killers is the aging process itself: Cancer, heart disease, dementia, and many more health problems become radically more common as we get older. We all know that factors such as smoking, lack of exercise, and poor diet can increase the risk of chronic diseases, but these are relatively minor compared to aging. For instance, having high blood pressure doubles your risk of having a heart attack; being 80 rather than 40 years old multiplies your risk by ten. As the global population ages, the magnitude of death and suffering caused by aging will only increase.
But this isn’t my prediction—apart from being depressing, extrapolating a two-century trend for a further year is hardly groundbreaking. What’s far more exciting is that, in 2023, we may see the first drug that targets the biology of aging itself.
Scientists now have a good handle on what causes us to age, biologically speaking: The so-called “hallmarks” of the aging process range from damage to our DNA—the instruction manual within each of our cells—to proteins that misbehave because of alterations to their chemical structure. Most excitingly, we now have ideas of how to treat them.
By the end of 2023, it’s likely that one of these ideas will be shown to work in humans. One strong contender is “senolytics,” a class of treatments that targets aged cells—which biologists call senescent cells—that accumulate in our bodies as we age. These cells seem to drive the aging process—from causing cancers to neurodegeneration—and, conversely, removing them seems to slow it down, and perhaps even reverse it.
A 2018 paper showed that in experiments in which mice were given a senolytic cocktail of dasatinib (a cancer drug) and quercetin (a molecule found in colorful fruit and veg), not only did they live longer, but they were at lower risk of diseases including cancer, were less frail (they could run further and faster on the tiny mouse-sized treadmills used in the experiments), and even had thicker, glossier fur than their littermates not given the drugs.
There are more than two dozen companies looking for safe and effective ways to get rid of these senescent cells in people. The biggest is Unity Biotechnology, founded by the Mayo Clinic scientists behind that mouse experiment and with investors including Jeff Bezos, which is trialing a range of senolytic drugs against diseases like macular degeneration (a cause of blindness) and lung fibrosis. There are many approaches under investigation, including small proteins that target senescent cells, vaccines to encourage the immune system to clear them out, and even gene therapy by a company called Oisín Biotechnologies, named after an Irish mythological character who travels to Tir na nÓg, the land of eternal youth.
Senolytics aren’t the only contenders, either: Others currently in human trials include Proclara Biosciences’ protein GAIM, which clears up sticky “amyloid” proteins, or Verve Therapeutics’ gene therapy to reduce cholesterol by modifying a gene called PCSK9. The first true anti-aging medicine will very likely target a specific age-related disease driven by a particular hallmark, rather than aging writ large. But the success of a drug targeting an aspect of aging in clinical trials will allow us to consider this loftier goal in the not-too-distant future.
In 2023, early success of these treatments could kickstart the greatest revolution in medicine since the discovery of antibiotics. Rather than going to the doctor when we’re sick and picking off age-related problems like cancer and dementia in their late stages when they’re very hard to fix, we’ll intervene preventively to stop people getting ill in the first place—and, if those treadmill-shredding mice are anything to go by, we’ll reduce frailty and other problems that don’t always elicit a medical diagnosis at the same time.
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