How old are you really? Birthdays may be a common tally, but your “age” isn’t determined by time alone. New research increasingly shows the importance of considering chronological age as something very different from biological age—in which the body and its cells, tissues and organs all have separate “clocks” that can tick at different speeds.
“Calculating biological age, I think, is core to the advances we have made in the science of aging,” says Eric Topol, a cardiologist and genomics professor at Scripps Research in La Jolla, Calif. “It’s a way you can tell if a person, organ or any biological unit is at pace of aging—if it’s normal, abnormal or supernormal.”
In his newest book, Super Agers: An Evidence-Based Approach to Longevity, Topol delves into the recent surge in public interest in biological aging and the accelerating quest to refine ways of measuring it. Improved biological timekeeping can give a more precise picture of a person’s longevity prospects and of potential ailments that can be prevented or treated early. Scientific American spoke with Topol about the latest research in biological aging, factors that might speed it up or slow it down, and what it can tell us about our current and future health.
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An edited transcript of the interview follows.
How is biological age determined, and how has the research evolved?
This research was really started more than a decade ago by geneticist Steven Horvath with his “clock” test, with which, basically using saliva, you could look at specific genetic markers and predict a person’s biological age. His clock is really known as an epigenetic clock or methylation clock. As people age, DNA changes and gets methylated—a methyl-group molecule attaches to specific nucleotides of DNA. I kind of liken it to the body rusting out. Essentially you’re getting marks at specific parts of the genome that track with aging in humans and every other species of mammal.
In Horvath’s initial test, there clearly was a detection of both alignment with the person’s real age, or chronological age, and when it wasn’t matching up. In other words, if a person’s biological age was off by a few years from their real age, you’d wonder why.
Then what’s proliferated in the more than 10 years since has been all these other clocks: protein clocks, RNA clocks, immune system clocks—you name it. Using plasma proteins from a blood sample, we can also clock organs—the heart, brain, liver or kidney. So we have seen just enormous advances in these clocks, and they keep getting refined with added features. There’s a race to get the best clocks to predict survival.
What can biological age tests tell us clinically?
We can detect in an individual if something’s not right at different levels. For example, if your biological age is five years older than your real age, is there an organ that might be linked with that? Then you can use these clocks to see whether lifestyle changes, prevention or treatment can slow down the pace of aging and get it into alignment with your actual age.
Improved biological timekeeping can give a more precise picture of a person’s longevity prospects.
The question is: When will doctors actually start using them? The medical community is very hard to change. So it hasn’t happened yet, but I believe it will eventually. Tests are also made available by commercial companies, but they can be very expensive. You can run an epigenetic test in a very simple way for $10 or $20, but some of these companies are charging $200.
I haven’t seen their publications to be able to say with confidence that they are doing things right, and the lack of standards from one company to the next is disconcerting. They don’t want to shock customers by telling them that they’re 10 years older than their chronological age. Eventually, I believe, we’re going to have high-fidelity epigenetic clocks with no motivation for a provider to hold things back if a person’s data are really bad.
Why might someone biologically age “faster” or “slower” than they do in actual years?
If you had to pick one mechanism behind why biological age and chronological age are misaligned, it would most likely be that some genes are either protective or linked with accelerated aging—but that’s such a small part of the story. Another root cause appears to be that our immune system gets weaker and less functional as we get older. In the average person, this change starts around age 55 to 60. The immune system’s level of protection drops, or it gets dysregulated—off track—and it can have an untoward, hyperactive response. When that happens, you start to see inflammation in the organs, such as in the arteries of the heart or the brain—it’s what I call “inflammaging.”
Obviously our lifestyle also has a big impact—eating a really healthy diet that’s not proinflammatory and doesn’t have a lot of ultraprocessed foods or red meat is beneficial. Good sleep health helps to reduce inflammation. There’s only one thing that’s been definitively shown to slow the epigenetic aging process, and that’s exercise. I think these clocks ultimately are going to be very good incentives for people to adopt a healthy lifestyle. We can’t get everybody to do all these things that we know help them, but if they get their own data and see something’s off track, the hope is that they’d change their habits. That’s, of course, just one of the ways to prevent diseases. There are also drugs and other treatments.
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What environmental factors are also important to consider?
We have all kinds of food deserts in the U.S. We have air pollution and unmitigated accumulation in the air and water of microplastics and nanoplastics, which get into every part of our body and induce inflammation. And we have forever chemicals that are pervasive. These all play a role in health and aging.
Let’s talk more about inflammaging. We know some inflammation can be good for the body—to fight infections, for instance—but a lot can be bad. How does chronic inflammation potentially accelerate aging?
Inflammation and aging are so tightly intertwined. The immune system is really the driver for good when it attacks pathogens and for bad when it promotes too much inflammation in walls of arteries or the brain. That’s heart disease and neurodegenerative disease, respectively. But what’s so exciting is we can dial up or down the immune system now. For example, there have been natural, amazing experiments with the shingles vaccines, which reduce dementia and Alzheimer’s disease by 20 to 25 percent. So how does that work? Well, the vaccine amps up the immune system in people. That’s going to be the critical thing in using these metrics: zooming in on the immune system and inflammation to keep people’s immune system intact and stop it when it starts to go haywire. That’s the future. In the last chapter of my book, I presented the first cut of my “immunome”—an assay of every virus and pathogen I’ve been exposed to, every antibody I have. But that’s just scratching the surface.
The immune system clock could turn out to be the most useful of all; if I could pick one, that’s the one I would want. But the immune system is very complex. Maybe we don’t have to do a systematic, comprehensive assessment of our immunome that would include checking antibody titers and sequencing B cells, T cells and interferons. If we can use just a group of plasma proteins, that would be terrific. That remains to be seen. There’s a human immunome project just getting started to try to compare things such as the proteins with the much more sophisticated and expensive ways to get at the health of an immune system.
What are the downsides of slowing down biological aging or of extending lifespan?
We feel really great if we get to age 85. “Super agers” who don’t get one of the big four age-related diseases [type 2 diabetes, cancer, or heart or neurodegenerative disease] can say, “Well, I did it.” Of course, if you get to age 98, you’re really doing well. I think we’re going to have a whole lot more super agers. But that’s not going to get around the fact that eventually they’re going to develop some problems—one of the big four or other conditions. It could be you get an infection because your immune system is just too weak. Or it could be you break your hip because your bone density is so low, and you wind up with a pulmonary embolus [a clot that blocks blood flow to the lungs].
Eventually you die, and you may have a chronic illness between that point of extended health span and when you die. I don’t want to put a sense out there that super agers won’t see problems in the latter stages of their lives. But the point is, let’s extend the health span—high-quality life without these big age-related diseases—as much as we can before getting into the downturn of a health arc.
