Chronic diseases like cancer, heart disease and diabetes, first hit the average American in their 60s. Cancer is usually diagnosed at 66, the average age for a first heart attack in men is 65 (women catch up to men in risk for heart disease after menopause), and Type 2 diabetes often shows up at ages 45 to 64.
As diseases are diagnosed, doctors attack them. Often, they are not cured but managed and controlled. We now spend half our lifetime in declining health, and we battle chronic illness for one-fifth of it.
Many first experience a chronic illness through their parents. Aging Americans now live longer but do so with more diseases than the generations before them.
If one disease is managed, the patient can continue living until the next one pops up, after which this process is repeated. For that reason, some researchers believe that curing cancer might add only about 3 years of life because another disease will show up.
After age 65, most people have two or more chronic diseases. U.S. Adults in their 60s and 70s take up to five different prescription medications at a time. And what helps one condition may worsen another.
At about 76, the U.S. Life expectancy, the adult will probably die from one of these diseases.
“Our health care system and even biomedical research system have evolved to focus on individual diseases, and usually it’s from the perspective of waiting until people are sick and then trying to treat or cure their disease,” said Matt Kaeberlein, a biogerontologist (the study of the biological basis of aging and age-related diseases) at the University of Washington and chief science officer of Optispan, a company in the field.
“It’s not a perfect way to think about it. But in some ways you can think about that approach as if you were in a jet aircraft, and instead of doing preventative maintenance while the aircraft was on the ground, you wait until something breaks when you’re at 35,000 feet and try to fix it.”.
Pushing diseases back
All of these chronic conditions share a risk factor: age. It may be the process of aging itself that makes us vulnerable to these diseases, which affects our health span (how long we stay healthy) and life span (how long we live.) As we get older, we lose strength and mobility as our bodies undergo molecular changes that eventually undermine their integrity and resiliency. Scientists refer to these changes as hallmarks. These include chronic inflammation and the accumulation of senescent cells, or “zombie” cells that stop multiplying because of damage or stress but don’t die as they are supposed to.
Some researchers believe that through addressing aging itself, diseases related to aging can be pushed back and possibly prevented. This would mean living healthier, longer.
“We’re all familiar with the idea that one human year is roughly seven dog years, and all that means is dogs age biologically about seven times faster than people,” Kaeberlein said. “So the important implication is that we can study that biology, start to learn about it and we have a potential to intervene in that biology to have a positive impact on disease outcomes and health.”.
Exercise is one intervention that can influence the biology of aging and is accessible to almost everyone. Someone who is fit, exercises, never smokes and drinks very little can expect to gain nine additional years without chronic diseases compared with a person with an unhealthy lifestyle, according to a study in 2020 in the journal JAMA Internal Medicine.
“If somebody asks you for advice, ‘What could I do now to help my aging?’ The answer really is just diet and exercise − there are no therapies yet,” said Kristen Fortney, CEO of BioAge, a biotech company developing drugs to treat diseases related to aging. “I think part of the focus there today is just due to the fact that really, that is the best we can do, but I think that (medical) interventions will take us potentially quite far beyond that.”.
The field is known by many names: longevity, geroscience, anti-aging. Regardless of the name, it’s still in the early stages. Several drugs may have the ability to postpone or prevent the onset of debilitating diseases. Animal studies have demonstrated their potential, and now clinical trials are beginning to assess whether their promise holds true in humans.
“I think it’s certainly legitimate to ask why we haven’t done that previously,” Kaeberlein said. “And in part it’s because we really haven’t had the knowledge base to be able to do that.”.
One promising drug is rapamycin. It’s an antifungal approved by the FDA as an immune suppressor to prevent organ recipients from rejecting a new organ. The compound was first discovered on the remote island of Rapa Nui, or Easter Island.
Rapamycin inhibits a protein called mechanistic target of rapamycin (mTOR). The protein senses nutrients and then controls cell outputs regulating many processes in the cell.
Giving rapamycin to yeast, worms, flies and mice prolonged their lives, studies have shown. Scientists began exploring rapamycin’s anti-aging effects in people, and studies suggest this immune-suppressing compound can actually improve immune function in older adults boosting their response to flu shots and lowering their odds of getting severely ill during cold and flu season.
As we age, immune function both declines and increases. Though the ability of our immune system to respond to pathogens declines, it can also overreact by striking in the absence of any threat. This can result in healthy tissues and organs being attacked, which can lead to chronic inflammation linked with various kinds of diseases.
So, what is causing the inflammation itself? One possible culprit is senescent cells known as “zombie” cells because they stop dividing but don’t die. They accumulate as we get older and give off inflammatory signals, which contribute to some age-related diseases.
According to Kaeberlein, rapamycin doesn’t kill the senescent cells but has an effect he describes as putting a gag on them, shutting off their inflammatory signals.
“I think that’s a pretty clear example where you can imagine multiple age related diseases being improved by a single treatment,” Kaeberlein said. He leads a rapamycin trial in dogs, which suffer similar age-related decline as humans but live much shorter lives.
Studies in mice have suggested that rapamycin may have beneficial effects on age-related cognitive decline and improve function of the heart and ovaries. The drug may also affect periodontal disease. Mice treated with rapamycin had less gum inflammation and even regrew bone around their teeth. But that doesn’t mean rapamycin will work in people.
“People have done lots and lots and lots of experiments in invertebrates. And of course, mice are very different from humans, right?” Says Fortney.
“Mice never die of heart disease. It’s one of our No. 1 killers when you’re older. They never get Alzheimer’s disease.”.
Researchers started several clinical trials to test the effects of rapamycin in humans. However, there are many challenges in testing these interventions in humans. Because people age slowly, it could take decades to learn whether a drug improves health span.
One potential solution to this problem involves biomarkers, trackable biological measures that change across smaller time frames and can also be used to monitor the effectiveness of anti-aging drugs. For example, researchers could track the addition of certain chemical groups to DNA. However, biomarkers would need to be chosen carefully, because a drug could affect a biomarker but not the disease itself.
“I was very involved in the push to do longer-term outcome trials for diabetes and I think the payoff has been stupendous because I don’t know how long it would have taken us to distinguish the Type 2 diabetes drugs that reduce death and major events from those that lower glucose but don’t have much additional impact,” said Food and Drug Administration Commissioner Dr. Robert Califf at the Targeting Healthy Longevity 2023 Conference.
Is aging a disease?
If a drug is ever to be used as an anti-aging therapy, it’ll need to be tested in healthy people who are aging naturally the way that new drugs for a certain illness are tested on people who have that disease. However, aging isn’t officially defined as a disease. One clinical trial aims to prove that aging is something that can be targeted and treated. It involves metformin, long used to treat Type 2 diabetes. People with diabetes who took the drug, which costs about $20 for 60 tablets, outlived people who did not have diabetes and did not take the drug, according to a study. Other studies have also demonstrated metformin’s ability to prevent specific age-related disorders.
In a trial called Targeting Aging With Metformin (TAME), researchers will track 3,000 adults 65 to 80, who will take the drug for six years. The goal is to see if metformin can prevent or delay three age-related diseases: dementia, heart disease and cancer. This will show if metformin can increase health span. If the trial succeeds, it may show that drugs to target aging don’t need to be expensive and can be available to more people, not just the rich.
The trial has struggled to raise funding − partly because metformin is a generic drug, which reduces potential profits for drug companies. That’s one of the major challenges for the field − basic research and studies of potential interventions are underfunded.
Senolytic drugs are another promising therapy. Instead of shutting off signals from senescent cells, like rapamycin, this treatment seeks out and kills these cells. Several efforts are already underway to test senolytics in specific age-related diseases like macular degeneration, diabetes, obesity and Alzheimer’s.
These are only some examples of the many strategies that seek to target various aspects of aging. Hundreds of companies in longevity biotech are working to translate the discovery of drugs that extend health span in animals into human treatments. Investment in the field has been growing with some companies getting millions in funding, like Calico, a Google-backed company, and Altos Labs, a Jeff Bezos-backed company.
Trying to prove a drug can extend health span is long and expensive because randomized clinical trial for longevity in people would take years. Instead, many companies in the field test a drug first for its ability to treat a specific illness. And once the drug is approved for that one illness, it may go through clinical trials again to test it broadly and see if it can treat other conditions.
Learning from the healthiest
Some people age more slowly than others. They look younger than their peers and get chronic disease later than the average person.
“There’s a lot of people around us who live to be 100 or even 110,” said Fortney, the biotech executive. “They’re very independent and not in a nursing home until a very old age. They are still mentally sharp. So there’s all these walking human examples (showing) that we can do better.”.
Fortney’s company BioAge uses AI to analyze the distinctive molecular features of people who live the healthiest, longest lives and applies that knowledge to the development of therapies that could help others live longer.
“They figured out how to do it,” Fortney said. “By studying their biology, we might learn clues to help the rest of us get there.”.
One of the drugs the company is testing is for muscle atrophy. As we get older, we lose muscle mass, and after age 30, the body begins to lose up to 3% to 5% of muscle mass a decade. Most men will lose about 30% of their muscle mass during their lifetimes. Less muscle means increased risk of falls, which are a major cause of accidental death in older people.
BioAge has already showed that its drug prevented muscle atrophy in elderly on bedrest. The company now is moving to the next phase of the clinical trial.
A panacea for living forever?
Despite the promise of this field, Fortney cautions against expecting too much.
“There’s not going to be a silver bullet where you just take one drug and suddenly your life changes by 50 years,” Fortney said. “But I do believe − and this is just a hunch − that adding 10 or 20 years to average health span is going to be within the near-term possibility from what we’re working on here.”.
Just as people take statins today to lower cholesterol and prevent strokes and heart disease, medicines could be prescribed to prevent diseases related with old age based on the results of a blood test, which could indicate how fast you’re aging and which diseases you’re prone to.
It could also mean a change from the prevailing medical model, where diseases are treated after symptoms have occurred and suffering has set in, to a preventative model of care, where patients are monitored proactively, and future diseases are delayed and potentially even averted.
“The current system has done a reasonably good job at keeping sick people alive,” Kaeberlein said. “Really hasn’t done a very good job at keeping people healthy longer. … The goal really should be to try to keep people healthy as long as possible to maintain the highest quality of life as long as we possibly can.”.
That means that any potential longevity drug would really be a preventive medicine, because it would delay age-related diseases.
“People have said if there’s a disease it’s going to kill my child before they’re even 10 years old I’m willing to take more risk in order to potentially get a benefit but when you’re talking about healthy people we haven’t come to grips with that yet, like there’s a question how much uncertainty is reasonable for people to tolerate,” Califf said.
According to Califf, the discussion about where to draw that line should involve experts in the geroscience and other fields as well as the National Institutes of Health, the Centers for Disease Control and Prevention and other federal agencies.