By Alexandra Ossola
The scuttlebutt around Silicon Valley is that soon we’ll soon live way, way longer. Former Googler Bill Maris says humans can make it to 500 years old; hedge fund manager Joon Yun thinks 1,000 years is more on the money. Some, such as biotech founder Martine Rothblatt, have even called death “optional.” Silicon Valley entrepreneurs are not the first to be obsessed with longevity — the rich and powerful of many societies have fixated on immortality. But the advances made in medicine and technology over the past century may have positioned today’s tech elite to make significant progress toward extending the human lifespan.
There’s just one problem: More life doesn’t necessarily mean a better life. At a certain point, parts of the body stop working properly, making it difficult to enjoy the time you’ve got. Medical conditions like Alzheimer’s, cancer, diabetes, heart disease and arthritis can make the final years of one’s life an exercise in suffering. Living for 1,000 years isn’t much of a boon if only the first 80 — or even the first 900 — are physically pleasant.
“Living for 1,000 years isn’t much of a boon if only the first 80 — or even the first 900 — are physically pleasant.”
Luckily, there are also scientists working to extend the amount of time during which a person is healthy. Some interventions seem more realistic or pragmatic than others, but it’s becoming clear that getting sick with age is anything but inevitable. These approaches might even change the way we think about the very concept of getting old.
“Our goal is not to extend longevity at the cost of being unhealthy for 75 years — our goal really is to take and extend the amount of time we’re healthy and compress the time we’re in morbidity,” says Derek Huffman, a professor of molecular pharmacology and medicine at the Albert Einstein College of Medicine.
What’s health, anyway?
Scientists refer to the number of years a person is healthy as the health span, but measuring that is tricky. A person is considered healthy if the body is generally functioning as it should, with no signs of disease. It’s not a coincidence that age is the biggest risk factor for chronic conditions like Alzheimer’s, diabetes, and heart disease — as we age and our cells break down, chemical reactions that clear away waste happen slower or less frequently, and there are fewer stem cells around to replace malfunctioning tissues.
Researchers have spent decades trying to make animals such as monkeys, mice, and roundworms live longer. Along the way they’ve figured out some techniques that keep them healthy longer, too. Starting in the 1930s, experiments on mice have shown that drastically reducing the calories in their diet not only extends their lifespan, but their health span, too (the findings have been repeated a number of times, most recently in monkeys).
“Pathologies associated with disease seem to be postponed in caloric-restricted mice, and some pathologies never appear,” says Gordon Lithgow, a professor at the Buck Institute for Research On Aging specializing in the mechanisms of aging. That’s where scientists got the idea that extended life and extended health may work hand-in-hand, Lithgow says.
From the caloric restriction studies, scientists have started to identify a few major biological pathways — chains of chemical reactions within the body — that likely play a key role in aging. Some, such as one that makes a hormone called insulin-like growth factor 1 (IGF-1), correspond to growth; studies have indicated that reducing its activity in older but healthy animals delays the signs of aging. Others, such as an immune signaling protein called Interleukin 1, are tied to inflammation, the immune system’s destructive reaction to something it perceives as a threat; dialing down the pathways that signal inflammation in the body seems to keep animals from aging.
Of course, humans aren’t mice or monkeys. But researchers can still learn a lot from these animal models. Some types of signals haven’t changed much as humans have evolved, and “it’s a good bet they will be operating in people,” says James Kirkland, a professor of aging research at the Mayo Clinic.
Genetic analyses into long-lived humans called super-agers can give researchers a clue on where to start looking. There aren’t many who live past age 100 — the 2010 census revealed just over 53,000 centenarians in the entire United States — but those who do tend to stay healthy for much longer than the rest of the population, and tend to die of acute conditions like pneumonia as opposed to lingering ailments like cancer or heart disease.
But actually testing anti-aging therapies in humans is much more difficult than checking in on super-agers. Clinical trials that evaluate the human health span would require decades, and billions of dollars. So researchers have been looking for biomarkers of aging, biological indicators to show them if a particular intervention is working as they hoped. Though there is no clear protein or genetic mutation that scientists can detect to show aging, they can measure things like abdominal circumference, blood pressure, telomere length, body mass index, and frailty index to get a sense for how much a person has physiologically aged.
Though the scientific community has more or less agreed on the types of pathways that play a key role in aging and related diseases, it is far from reaching a consensus on how best to alter them.
Years of experimenting on animals has shown that caloric restriction is a non-invasive and effective way to slow the biological signs of aging. But, save for a few small and dedicated communities of human calorie-restrictors, it’s hard to convince people to override their biological desire to eat enough food to feel full. There’s good evidence that exercise can slow aging, too, but exercise alone usually isn’t sufficient to make a significant impact.
Pharmacological interventions can more easily fit into people’s lifestyles. And, luckily, there are a few promising candidates — Kirkland estimates that there are 50 drugs or interventions that affect the appropriate pathways, with peer-reviewed studies on about a dozen of them. One, called metformin, has been on the market for years as an inexpensive treatment for type 2 diabetes. Numerous experiments, including some in mice, show that the drug is a promising anti-aging option. A 2014 study found that diabetics taking metformin outlived not only other diabetics not taking the drug, but also unmedicated non-diabetics. Researchers are now testing metformin in the first-ever FDA-approved clinical trial for a drug to combat aging.
Another trial of a drug called rapamycin, originally developed to suppress the immune system after an organ transplant, has shown spectacular results in mice and in dogs. But it has more side effects, such as (rather ironically) an increased risk of developing type 2 diabetes. Furthermore, many of the drugs found to work in mice have a lot of variation across individuals — and even appear to affect male and female rodents differently — which makes them less appealing options for human trials.
Parabiosis, a decades-old experiment in which scientists connect the circulatory systems of young and old rodents, has gotten more attention in the past few years thanks to billionaire Peter Thiel, who told Inc magazine that he is interested in injections of young blood to extend the human health span. But although a controversial clinical trial recently concluded that young blood can have anti-aging effects, most researchers, including Huffman, see parabiosis as an experimental tool to figure out new anti-aging targets for a future drug — not as a viable treatment in and of itself.
Looking into the far future, genetic engineering using tools like CRISPR may be an option to increase health span. But the prospect is so distant — and so ethically fraught — that researchers can’t seriously consider it. “It’s premature to talk about CRISPR, because no one has done it yet in lab animal. I think it’s irresponsible to talk about doing that in people,” says Matt Kaeberlein, a pathology professor at the University of Washington.
Others think it’s best to start having those difficult conversations early. “It’s a really good question for an ethics class. If we could do [genetic engineering] today and it would affect the next generation, would you do it?” Lithgow says. “Until we understand the trade-offs, we can’t engineer the next generation.”
Still, some in the field are skeptical that these interventions will work as well as hoped. Luigi Fontana, a professor of geriatrics and nutritional science at Washington University in St. Louis, is compelled by the evidence for caloric restriction and the effects of exercise. But genetic engineering is unrealistic, he says, and metformin is “bullshit.” “This is willful thinking of people selling dreams,” he adds.
Even within the field of aging research, a consensus seems difficult to achieve. “When you’re having conversations in the field, everyone has bias, saying they think this pathway or factor is most important,” Huffman says. “It’s a problem for the field right now.” But fundamentally, these researchers all have the same goal: to make humans live healthier for longer. Their mission may just be lacking a champion — and a cohesive rallying cry.
A shift in medicine as we know it
As researchers work to develop and test ways to slow aging, they will first look to create treatments intended for people in their 50s and 60s, when chronic diseases often start to set in. Studies evaluating those treatments, some of which are already planned (most notably the trial for metformin), should only take a few months or years, measuring secondary indicators like BMI and frailty instead of death itself to ensure their efficacy. Eventually, there might be drugs for people to start taking when they’re even younger.
But giving pharmaceuticals to healthy people is a hard sell. Without extensive long-term clinical trials, it’s impossible to anticipate how the decades-long use of an anti-aging drug will affect other aspects of long-term health. There will almost inevitably be some side effects, and the public will have to wade through discussions of whether or not it’s worth it. “Anyone who tells you there’s no risk [to an intervention] is lying to you,” says Kaeberlein. There are people who question whether the clinical trials needed to prove the safety and efficacy of such therapies are even ethical, Kaeberlein adds.
These issues hint at a deeper ideological hurdle stopping anti-aging treatments from becoming commonplace. For now, our medical system is designed to address medical conditions as they arise. Putting interventions to treat aging on the market would mean a fundamental shift in our medical system, towards preventative medicine. “We’ve been trained in biomedicine to focus on sickness rather than health, so that paradigm shift will take time,” Kaeberlein says. And to move from success in the lab to having an actual impact on human wellbeing, he adds, you need to have public opinion on your side.
Social acceptance of aging interventions could pave the way for the medical shift. The field of anti-aging research suffers from what Kaeberlein calls a “reputation problem.” For decades, products running the gamut from skin creams to herbal supplements have claimed to have “anti-aging” properties, with virtually no science to back them up. “People associate our field with snake oil. That only adds to that perception that it’s not rigorous,” Kaeberlein says. What’s more, people in general are reluctant to talk about getting old and dying.
For now, researchers are still trying to get the U.S. Food and Drug Administration (FDA) onboard. As it stands now, the FDA only approves treatments for a specific medical condition — Prozac, for example, was first approved to treat depression, Lipitor to treat cardiovascular disease. Now researchers in the field of aging are trying to convince the agency to make a separate designation for preventative medicine. From the FDA’s perspective, the field of medicine built around combating aging is still in its infancy. “A question not yet answered is how many aging-related but otherwise independent diseases (coronary artery disease, dementia, sarcopenia, etc.) would need to be improved for us to consider the therapeutic effect an ‘anti-aging’ effect, rather than an effect on specific diseases. It is worth noting again that a drug that improved ANY of these conditions would be very valuable,” an FDA spokesperson said via email. It’s also still a challenge to figure out how to measure whether or not these interventions are effective. “The FDA is looking forward seeing this area of science evolve,” the spokesperson added.
“If the field of aging is going to move forward in having drugs to treat aging in humans, we’re going to have to have an FDA-approved pipeline to do so,” Huffman says. Having that framework in place will drive innovation, researchers claim—more research money can be allocated towards prevention, and pharmaceutical companies will work to develop new drugs that could potentially be used by the entire adult population. Though Kirkland doesn’t believe there will be a special designation for anti-aging interventions anytime soon, he does say that the FDA has been supportive and encouraging in their field. A clear FDA pathway, plus more frank public discourse, could give the field a reputation to match the rigorous science already underway.
Other issues will arise. Though people who stay healthy for longer would likely benefit the economy and would reduce burdens on the healthcare system, there may be a disparity between socioeconomic classes as the wealthy shell out for life extension (this is already the case, but the disparity may become more pronounced). And as humans live longer, brand new diseases could emerge. This isn’t a hypothetical problem: over the past century, during which rates of heart disease and strokes have dropped, Alzheimer’s has become more and more commonplace. “It’s highly unlikely that anyone during the Stone Age saw Alzheimer’s,” Lithgow says. But as people began to live longer, there was more time for particular physical problems to unfurl and accumulate. Our genomes likely have more surprises waiting for us.
But that’s no reason to stop, scientists argue. “Even if there are downsides, I don’t see that as an argument to not do [the research],” Kaeberlein says.
And it seems increasingly likely that some intervention or another will emerge to keep people healthy for longer. “20 years ago, I would have said [finding a way to extend the health span] had a .5 percent chance of working. It’s up to a 25 percent chance now, and every year it’s going up,” Kirkland says.
Just when such a treatment will be ready for broad use will depend on how quickly these shifts happen. But researchers are putting the pieces in place from scientific, regulatory, and social standpoints.
The real question, of course, is whether individuals are ready to live significantly longer, dying in worlds radically different from those into which they were born. Given humans’ perpetual desire to live forever, it seems unlikely that many would throw away such an opportunity. What we would actually do with it — and whether it would make us happy — is another matter entirely.
This article originally appeared on Popular Science.