April 25, 2023 – Measuring biological aging has become so precise with DNA-based technology that researchers showed that trauma or stressful life events can rapidly speed up the pace of aging. But they also found that recovery from the experience can return aging to its baseline.
This is one of the first studies to show that aging doesn’t have to happen in one direction. It may be too early to shred your AARP membership card, but the evidence in mice and humans looks promising.
“People just assumed that as you get older, your biological age goes with it. And that is correct, but there are fluctuations,” said James Patrick White, PhD, co-senior author of the study and an assistant professor of medicine at Duke University in Durham, NC.
Even though we all go through stressful events, its effect on aging can change rapidly.
“You might be stressed out, you might have some trauma, you might have whatever your stressor is that'll accelerate [your aging],” said White, who is also a senior fellow in the Center for the Study of Aging at Duke.
“The question was always: Well, are you stuck there? And we're showing this is not the case. You can reverse back a little bit once that stressor is removed,” he said.
The study was published online April 21 in the journal Cell Metabolism.
Turning Back the Clock
White, co-senior author Vadim N. Gladyshev, PhD, and their colleagues found that pregnancy, getting a hip fracture, and having severe COVID are traumatic or stressful enough to speed up aging. In contrast, having elective surgery did not speed up aging in the short term.
The idea that aging is not a one-way street comes in part from mice experiments. Joining two mice together – one young and one old – so they share the same blood circulation is a technique called parabiosis. The technique has been around for decades. But now, "the novelty here is one we show epigenetic acceleration. The young mouse gets older, the old mouse gets younger. And the cool thing is that when we then separate the mice and take away the old blood, the young mouse reverses that accelerated aging back to its chronological age,” White said.
The research was possible because of advances in measuring DNA methylation. Investigators can now look at individual sites on DNA where methylation predictably occurs over time. The sensitivity of these second-generation “DNA methylation clocks” has increased to the point where they can show changes in biological aging measured in days or weeks.
White and colleagues used blood samples from older patients before emergency hip surgery, the morning after, and 4 to 7 days into recovery. They found significant increases in biological age markers. “Remarkably, this increase occurred in under 24 hours, and biological age returned to baseline 4 to 7 days post-surgery,” the researchers noted.
They found that there weren't any significant changes in biological age markers linked to elective colorectal surgery in other patients.
Not All Stress Is the Same
In general, the aging process for people returns to its normal baseline after a stressor is removed. But there can be differences between people, with some returning to their former chronological age completely, some partially, and others not at all.
“That opens up the question of, 'Why?'” White said.
As an example, when they compared people who recovered from severe COVID, aging tended to rebound more among women than men. The reason is unknown and could be examined in future studies.
Resilience also counts.
“I would imagine if you can't cope with something and the stress stays up, you're going to accelerate biological aging and open yourself up to age-related issues, probably sooner than somebody that can recover," White said.
Another unknown is whether psychological and physical stress contribute equally to this aging acceleration.
Aging Not a ‘Nonstop Kind of Decline’
“I do see this as a breakthrough,” said Florence Comite, MD, a Yale-trained precision medicine doctor and founder of the Comite Center for Precision Medicine & Health in New York City, when asked to comment.
“I myself have always believed that aging doesn't happen in a steady state of decline,” she said. There are a lot of issues that are going on under the surface, she continued, including changes in muscle, hormones, metabolism, and the way the body puts down visceral fat into different organ systems. Family history and genetics can also alter aging.
Comite thinks of aging “as more of a stop/start kind of thing … not a steady, nonstop kind of decline.”
“I think that this will give us an opportunity to dig deeper,” she said. “It's just going to be the beginning of blowing the field open.”
Comite co-authored a 2022 study that looked at DNA methylation and COVID. Results showed people over 50 years old were more likely to have faster biological aging with COVID than younger people.
Overall, the finding that people can reverse a negative effect of stress or trauma is positive.
“We have a lot more reserve than we think we do or give ourselves credit for," White said.
Interventions to turn off the acceleration of aging linked with stress or trauma would most likely work for people with chronic disease, chronic effects of disease, serious infections like COVID, or even cancer, Comite said. But they would be unlikely to help people dealing with the general stress of everyday living, she said.
In the future, the technology also could be used to see how well anti-aging drugs work.