For many people, aging feels like it happens in stops and starts. After a period of smooth sailing, one day, seemingly out of the blue, you have achy knees.
“You wake up in the morning and you suddenly feel old,” said Dr. Steve Hoffmann, a computational biology professor at the Leibniz Institute on Aging in Jena, Germany. “That’s sort of the takeaway.”
It turns out there may be a scientific basis for this experience. By analyzing age-related markers, such as proteins and DNA tags in the bloodstream, some scientists are coming to understand that aging in adulthood is not a linear process, but perhaps one that jumps dramatically at certain points in one’s life.
Here’s what they’ve learned so far, and what it could ultimately mean for your health and life span.
What does ‘nonlinear aging’ look like?
Scientists have long suspected that aging may happen in bursts, but they only began using molecular signals to measure the pace of aging in the past decade or so.
A widely covered Stanford study published last year tracked several molecular changes associated with aging in blood samples gathered from 108 adults between age 25 and 75. By comparing samples from different subjects of different ages, it found that people seemed to age more rapidly around age 44, and again around 60. The clusters of changes in the first spike appeared to be mostly related to fat and alcohol metabolism, as well as muscle function, and the second spike mostly to immune dysfunction and muscle function. The first spike could help explain why people seem to have more trouble processing alcohol starting in their 40s, and why they become more prone to illness in their 60s, said Michael Snyder, a professor of genetics at Stanford Medicine and study coauthor.
Also last year, a study on mice coauthored by Dr. Hoffmann found that sudden chemical modifications to DNA occurred in the rodents’ early-to-mid life and again in mid-to-late life, suggesting there were three discrete stages of aging.
And in a 2019 study looking at the blood plasma of over 4,000 people, scientists reported there were significant jumps in concentrations of proteins associated with aging in the fourth, seventh and eighth decades of life.
Other experts think aging doesn’t necessarily happen in short spurts, but rather in longer phases. Steve Horvath, who is widely considered to have pioneered the biological aging tools known as epigenetic clocks, said a 2013 study he conducted found that the rate of aging follows a steep curve from early childhood until puberty, but becomes linear after age 20. (Dr. Horvath is now principle investigator at Altos Labs, a biotechnology company focused on improving cell health and slowing aging-related disease.)
There’s also early data suggesting that certain organs — such as the heart or brain — may age faster than others, said Tony Wyss-Coray, a professor of neurology and neurological sciences at Stanford University who was an author of the 2019 study.
Whether they happen in phases or spurts, it’s not yet clear how all of these molecular changes actually contribute to aging and age-related disease. Still, these types of findings could offer more insight into the biology underlying well-known shifts in middle age, such as slowing metabolism, said Allison Aiello, a professor of epidemiology at the Robert N. Butler Columbia Aging Center.
In practice, it could mean that people could be more targeted in managing their health, focusing on specific changes and conditions that correlate with their particular age, said Aditi Gurkar, an assistant professor of medicine at the University of Pittsburgh’s Aging Institute.
What’s next?
These findings are “quite interesting, but I would say preliminary,” said Dr. Eric Verdin, the president and chief executive at the Buck Institute for Research on Aging. And it brings up a whole series of questions, he said: “What’s happening? Which organ or collection of organs is causing these big changes?”
There are other open questions, including if the changes vary from individual to individual or between the sexes, and how much lifestyle and behavior may contribute, since there’s increasing evidence that certain events — like pregnancy, trauma and adversity or even a Covid infection — can also accelerate biological aging.
Experts said they’re eager to answer these questions with longitudinal studies that track changes over a person’s lifetime. That method would account for differences in environment or lifestyle among subjects.
“If you really want to identify whether it’s a linear trend, or there’s these spurts that occur over very specific time periods, you’d want to follow the same people to see if they’re biological” changes, Dr. Aiello said.
So far, researchers are only “touching the surface” of how molecular changes relate to aging, said Dr. Luigi Ferrucci, the scientific director of the National Institute on Aging. By learning more, he added, they can help people live better longer and head off disease. “Instead of declining at 70, we can try to make it decline at 75, and gain five years of good life.”
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