How can you live to be 100? Ten years ago, scientists would have "focused on avoiding disease, keeping cholesterol low, blood sugar controlled, organs functioning within textbook 'normal' ranges," writes Taayoo Murray in Popular Mechanics.
That's not necessarily true anymore.
"Their bloodwork often doesn’t look perfect. In fact, it sometimes looks concerning. And yet, they live," Murray writes.
An investigation from Sweden has yielded some surprising information. In the case of longevity, perfection is the enemy of the "moderately optimal."
"Researchers analyzed tens of thousands of individuals over decades, tracking biomarkers like cholesterol, glucose, uric acid, and markers of inflammation," reports Murray. The study found centenarians "tend to cluster within moderately optimal ranges across many biomarkers, not necessarily the lowest or highest extremes," Murray writes.
Jordan Weiss, PhD, assistant professor, NYU Grossman School of Medicine, explained that the authors found that both centenarians and non-centenarians had alkaline phosphatase and lactate dehydrogenase levels above what clinical guidelines consider normal, but those guidelines were calibrated to younger, healthier populations. Higher total cholesterol does not decrease the likelihood of reaching 100, which runs directly counter to what we’d tell a 50-year-old. “So if a 78 year old comes in with mildly elevated cholesterol, the move might be to reach for a statin,” said Weiss, “but in this age group, that elevated number may actually be a marker of resilience, not risk. We need to revisit age-adapted reference ranges.”
A 100-year-old patient would, at first glance, require aggressive treatment for several warning signs of declining health. But are these less-than-perfect biomarkers the reason the patient is still alive?
Ida Mae would not be flagged as a model patient by most predictive health tools. With an A1C of 7.7 and creatinine of 1.05, she is diabetic with declining kidney function. In a younger patient, these numbers would trigger aggressive intervention. But longevity doesn’t always follow clinical logic. Her cholesterol profile, total cholesterol at 135, LDL at 53, is low and protective. Her liver enzymes are normal. More importantly, she has made it to 100 despite carrying risk factors that, statistically, should have shortened her life. This is the central paradox of centenarian biology. The presence of disease does not preclude exceptional longevity.
Here's the shocker.
Murray says, "Researchers in the field of gerontology increasingly believe that what distinguishes centenarians is not the absence of illness, but a unique ability to tolerate it."
The Swedish cohort study, drawing from national health registries and long-term blood data, identified several key patterns among those who reached 100. They have lower, but not extreme, levels of glucose and elevated creatinine. Participants tended to avoid the highest-risk categories, even if they weren’t perfectly controlled. While some participants had balanced cholesterol levels, even extremely low or high cholesterol did not increase or decrease the likelihood of reaching 100. Stability, not minimization, was protective. Elevated uric acid, linked to inflammation and metabolic stress, was a strong predictor of mortality. Perhaps most importantly, centenarians showed less volatility in their biomarkers across decades.
“Maintaining good function across multiple systems can lead to a higher likelihood of surviving longer,” said lead study author Shunsuke Murata, PhD.
The body has a unique ability to absorb stress —metabolic, inflammatory, and environmental. In centenarians, this translates into across-the-board, above-average biomarkers. "They had a profile, across metabolism, liver function, kidney function, inflammation, and nutrition, that was consistently more favorable," according to Dr. Weiss.
Many researchers believe there is something else at work, something hidden and beyond our current understanding. High blood sugar in a young person leads to vascular and heart damage. Why doesn't it lead to death in older people?
The big question scientists are asking is whether this research will lead to longer life.
This is where science becomes both promising and complicated. On one hand, the insights from centenarian blood studies could lead to more sophisticated risk models. Instead of treating any deviation from “normal” as dangerous, clinicians could adopt a more individualized approach, one that considers stability, trends, and overall resilience.
For example, a slightly elevated A1C in an older adult might be managed conservatively if other markers are stable. Cholesterol targets could be personalized rather than universally minimized.
This sounds like a job for artificial intelligence (AI). Indeed, juggling all of these biomarkers so that they end up helping, not hurting, patients requires a vast knowledge base and specific treatment regimens.
Most people I know only want to live to be 100 if they're reasonably ambulatory and still have most of their wits about them. Otherwise, going quietly while asleep sounds pretty good to me.
