One 50-year-old has the nimble metabolism of a teenager, while another’s is so creaky he developed type 2 diabetes — though his immune system is that of a man 25 years his junior. Or one 70-year-old has the immune system of a Gen Xer while another’s is so decrepit she can’t gin up an antibody response to flu vaccines — but her high-performing liver clears out alcohol so fast she can sip Negronis all night without getting tipsy.
Anyone over 30 knows that aging afflicts different body parts to different degrees. Yet most molecular theories of aging — telomere shortening, epigenome dysregulation, senescence-associated secreted proteins, take your pick — don’t distinguish among physiological systems and organs, instead viewing aging as systemic.
Nonsense, say scientists at Stanford University School of Medicine. In a study published on Monday in Nature Medicine, they conclude that just as people have an individual genotype, so too do they have an “ageotype,” a combination of molecular and other changes that are specific to one physiological system. These changes can be measured when the individual is healthy and relatively young, the researchers report, perhaps helping physicians to pinpoint the most important thing to target to extend healthy life.
“This really presents a new framework to think about aging,” said epidemiologist Norrina Bai Allen of Northwestern University’s Feinberg School of Medicine, an expert in the biology of aging who was not involved in the Stanford study. “It’s an important first step toward showing how different parts of a body in different people can age at different rates.”
Call it personalized medicine for aging. “Individuals are aging at different rates as well as potentially through different biological mechanisms,” or ageotypes, the Stanford scientists wrote.
“Of course the whole body ages,” said biologist Michael Snyder, who led the study. “But in a given individual, some systems age faster or slower than others. One person is a cardio-ager, another is a metabolic ager, another is an immune ager,” as shown by changes over time in nearly 100 key molecules that play a role in those systems. “There is quite a bit of difference in how individuals experience aging on a molecular level.”
Crucially, the molecular markers of aging do not necessarily cause clinical symptoms. The study’s “immune” agers had no immune dysfunction; “liver agers” did not have liver disease. Everyone was basically healthy.
If aging is truly personal, understanding an individual’s ageotype could lead to individualized, targeted intervention. “We think [ageotypes] can show what’s going off track the most so you can focus on that if you want to affect your aging,” Snyder said.
Cardio-agers, for instance, might benefit from tight cholesterol control, periodic ECGs, and screening for atrial fibrillation. Immune agers might benefit from diets and exercise to reduce inflammation.
Then again, they might not. The study did not follow people long enough to tell whether their aging biomarkers did them any harm, or were even harbingers of harm, let alone killed them, Feinberg’s Allen pointed out. “There needs to be a lot more work, and replication of the results,” before they can be the basis for anti-aging interventions, she said.
The short follow-up and small sample size — 106 people — gave other experts pause. One said he “will not comment on it in any way” and declined to elaborate.
One concern revolved around what might otherwise be the study’s strength: the dizzying number of measurements the scientists made on their volunteers, ages 29 to 75, over two to four years. Through blood and saliva and urine tests, genetic analyses, microbiome inspections of their nose and gut, and more, the scientists measured 10,343 genes, 306 blood proteins, 722 metabolites, and 6,909 microbes, among other things, and found they clustered into four ageotypes: liver, kidney, metabolic, and immune.
Different people had different “personal aging molecules” and “distinct aging pathways,” Snyder said. But just as every dish on a menu is unique but can be grouped into “meat” or “fish” or “vegan” or other category, so the molecules fell into the liver, kidney, metabolic, or immune ageotypes. (There is probably a cardio-ageotype and a neuro-ageotype, too, Snyder said, but they didn’t have enough data to characterize those.)
“That we don’t all age identically is well-established,” said biologist Judy Campisi of the Buck Institute for Research on Aging, who has helped develop an “atlas” of aging biomarkers. But the new study “furthers our understanding of why.”
All told, the study generated 18 million data points. While that sounds impressive, it raises the risk that some markers seem to be part of one or another ageotype just by chance.
But Snyder said he is “quite confident” the biomarkers are not statistical artifacts. For one thing, the researchers initially found 184 of them. But using stricter statistics, they narrowed that to 87.
In many of those opposites, the reason might be healthy lifestyle changes. People whose A1C fell significantly, for example, either started eating a healthier diet or lost weight, both of which can improve glucose metabolism. “Lifestyle changes, and perhaps medications, can improve some markers of aging and alter an individual’s aging pattern,” said Snyder (who is 64 and has a metabolic ageotype). In fact, 15 people got biologically younger during the study.
That healthy habits can increase both lifespan and healthspan is not exactly news. But the ageotype approach might let people target their dominant aging pathway.
“The hope is that once you identify the main cause of an individual’s aging, it opens the door to interventions — exercise or diet or intermittent fasting or medications,” said Campisi. “Ideally, a 50-year-old could get a blood test and learn that his kidney is 60 but his heart is 40, and do something about [kidney aging]. This is a step in that direction.”