Humans can effectively de-age after recovering from stressful events, a new study from Harvard Medical School and Duke University School of Medicine has found.
The breakthrough research shows that while stress can significantly age a person biologically the body can naturally reverse this effect, lowering your chance of mortality.
“These results highlight our own resilience,” senior co-author Dr James White, from the Duke University School of Medicine, told BBC Science Focus: “We don’t give enough credit that the body can reset.”
While chronological age represents the number of years you have been alive, biological age is defined by how much your DNA has been altered by a chemical reaction called methylation.
Your biological age is influenced by factors like disease, lifestyle, environmental factors. Stress, whether physical or mental, has also been found to rapidly age a biological clock.
The new study, published in Cell Metabolism, shows that your biological age is much more flexible than your chronological age. In fact, people can be biologically older or younger than their chronological age.
The researchers say that the discovery that biological age is “fluid, fluctuating and malleable” challenges the long-held belief that it can only go up, like chronological age. This research is the first to explore the question of ageing being reversible in humans.
In the study, researchers challenged the theory that somebody’s biological age is overwhelming determined by their chronological age – that methylation levels change predictably over time. Methylation levels were measured in human participants following surgery, pregnancy, and severe cases of COVID-19.
The researchers found that methylation levels in participants were different from the predicted levels for their chronological age. This meant their biological age was lower or higher (depending on the amount of methylation in their DNA) than their chronological age.
Severe stress has been previously linked to higher mortality rates by increasing biological age due to increased susceptibility to stress-related diseases.
In the same way, the new study shows that reversing your biological age can decrease your mortality. According to Dr Vadim Gladyshev, co-senior author of the study, this suggests that “the ability to recover from stress may be an important determinant of successful ageing and longevity” – in other words, how well we grow old.
The results of the study suggest that your biological age may now also be a useful measure of your stress levels and how well you have recovered.
As the study shows that our bodies are able to induce this reversal naturally, it provokes questions as to whether we might be able to reverse our age below the recovery baseline.
For the study, Duke University School of Medicine provided the mice samples which were then analysed by academics from Harvard Medical School, including first author Dr Jesse Poganik.
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Does recovering from stress – and reversing your biological age – make you visibly less old?
It’s almost a yes from Dr White, who says that “we wear stress, and I imagine that would translate to a physiological response”.
But is the kind of bad day that gives you dark circles under your eyes enough to accelerate biological ageing as much as surgery or, say, pregnancy? “Probably not”, says White. “But if you are stressed for months or years, that might be enough”.
It’s one of the key questions that the researchers are taking forward: how stressed you need to actually be before you accelerate your biological age – and therefore have the need to reduce it again. It also remains unclear whether we can bring down accelerated ageing over a longer time period.
If we want to help ourselves recover from stress, what should we do?
While the study did not pursue whether recovery must be active or passive, White speculates that a combination of physical and mental rest is important to recovery – and if either is lacking then the other will be limited.
Recovery is mostly a passive process, according to White, but an often-neglected aspect of recovery is the mental side which some people might need extra help with. For example, if you start walking again after surgery some people think “you must be better” – but it is important not to ignore the psychological aspect of recovery.
The results also showed some variability that suggests that some people might be better at recovering than others.
How did they find these results?
The study began with a process known as heterochronic parabiosis, which involves surgically attaching pairs of young and old mice together so they share one circulation. The infusion of young blood into the older mouse induces a reversal of its biological age – but for the young mouse, the stress of being exposed to aged blood increases its biological age. The study found that this was temporary, and the young mouse returned to its baseline biological age after recovery.
These initial results prompted the researchers to theorise that other stressful situations – such as pregnancy, getting serious cases of COVID-19, and experiencing major surgery – could also trigger reversible changes to biological age in humans.
They found that the rapid increases in biological age caused by emergency surgery can be restored to baseline just days after the procedure. And in the case of recovering COVID-19 patients, an immunosuppressive drug called ‘tocilizumab’ enhanced biological recovery.
What does this mean for the future?
As with much research, the results of this study perhaps throw up more than they answer – such as what the ‘common denominator’ is: the thing driving the stress in events like catching COVID-19 or pregnancy. Is it as simple as cortisol levels, or is something else involved? And, “just as importantly”, says White: “What needs to go down to reset biological age?”
Further research following this study will also tackle questions concerning differences between males and females, as well as the relationship between short-term fluctuations in biological and long-term trends: does short-term stress accelerate your ageing later in life?
About our expert
Dr James White is an assistant research professor in cell biology at Duke University School of Medicine. His research has been published in journals including Frontiers In Cell And Developmental Biology and Mechanisms Of Ageing And Development.
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