Stress makes you old – that sounds like a truism, but it has been proven in molecular biology: it ensures that epigenetic changes occur in the genome that shorten the lifespan of a cell. Researchers at Duke University School of Medicine are now showing that this process is not irreversible. They proved this with the help of laboratory mice, parabiosis experiments and special molecular clocks.
A person’s chronological age can easily be determined from their identity card. However, in order to measure its biological age, scientists analyze the genome. This changes its epigenetic structure over time. The genes of the genome remain the same, but because special methyl groups attach themselves to the DNA, some genes can no longer be read – others suddenly become readable.
These epigenetic changes follow a specific pattern, as demonstrated ten years ago by the German-American human geneticist and biostatistician Steve Horvath. At that time, he established the so-called Horvath clock, in which hundreds of DNA segments that are far apart in the genome are examined to determine whether and to what extent they are methylated. Software can now read the biological age from this. Scientists have now further developed Horvarth’s epigenetic life clock – the team from Duke University also used a special variant of the biological age clock for their investigations.
The scientists sewed young, only three-week-old laboratory mice together with older, twenty-week-old mice over a three-month period, and they shared a bloodstream. This procedure is called parabiosis. It is usually used in experiments where young blood is supposed to rejuvenate old animals. In this case, however, the scientists focused on what the blood transfusion actually means for the young mice. Would the old blood age them faster?
In fact, that’s exactly what happened. After the animals were separated again and the young mice were given two months to recover from the stress, the cells in their liver and other tissues were analyzed. Everywhere the epigenetic clock showed that the old blood had biologically aged the young mice. However, after the animals had sufficiently recovered, they became biologically younger again. In a second experiment, in which pairs of mice of the same young age were parabiotically combined, a few months after the separation of the two, a rejuvenation of the age clock was shown. The following applied to both experiments: “The parabiosis caused the young mice to age biologically, but they recovered after the separation,” the scientists write in “Cell Metabolism”.
So aging is reversible, at least a little bit
In further analyses, they also showed that the reversal of methylation, which had practically led to the biological clock being reset, also returned gene expression to the level that prevailed before the parabiosis.
But what do these experiments mean for the concept of aging?
“Classically, aging is seen as an ever-increasing accumulation of damage and loss of function, leading to illness and death,” says Vadim N. Gladyshev’s team. However, their study has now shown that this process is actually reversible. So aging is not an automatic downtrend.
Many people will be happy about that – after all, it fuels the hope of being able to rejuvenate oneself despite a high chronological age. The researchers now wanted to find out whether the observed turning back of the epigenetic life clock is only possible in laboratory experiments or also in real life. So they looked for potential stressors that occur naturally in life and accelerate aging. Surgery could be one such event, they surmised. So they took blood from accident patients immediately before hip surgery, immediately afterwards and again four to seven days later.
The effect also occurs after operations
It turned out as they had suspected: the cells aged quickly as a result of the intervention, but the corresponding epigenetic changes had already been reversed after seven days. Interestingly, they could not find any accelerated aging in the blood of patients with planned surgeries or colonoscopies – perhaps the trauma from the interventions and the associated stress were not so great.
The scientists continued to search for natural age accelerators – which are reversible. They found what they were looking for: Both pregnancy and inpatient treatment of Covid-19 disease put the epigenetic life clocks forward, but in the recovery phase they were then reset to the previous value.
What does all this mean? The scientists have provided evidence that stress accelerates cellular aging – but that recovery phases can reverse this process. From a biological point of view, aging is not a one-way street. This means that the hopes that many people have in anti-aging drugs are far from overblown. Since the cell clocks can be adjusted within a short period of time, active substances could also have a similar effect. It will be interesting to see which substances will be able to do this.
