What are the dynamics of biological age? – Harvard Gazette

In preclinical and human models, stress from surgery, pregnancy, and severe COVID-19 increased signs of biological age, which were reversed after recovery.

“Traditionally, biological age was thought to increase, but we hypothesized that it was actually much more dynamic,” the lead author said. Jesse the pagan of the Brighams Genetics Division. “Severe stress can trigger an increase in biological age, but if this stress is short-lived, the signs of biological aging can be reversed.”

For the study, Poganik and colleagues collected data on several situations that can cause severe physiological stress. In one experiment, they looked at blood samples from elderly patients undergoing emergency surgery, looking at samples taken immediately before surgery, a few days after surgery, and before hospital discharge. The team also looked at blood samples from pregnant mice and pregnant women, looking at samples from early and late stages of pregnancy and after delivery. And in a third analysis, the team looked at samples from patients who tested positive for COVID-19 and were admitted to the intensive care unit. They analyzed samples taken when the patient was admitted to intensive care and samples taken during his stay. The team also used a classic mouse model in which, through surgery, the circulatory systems of younger and older mice are brought together.

The team used “biological clocks” to determine the health of cells and tissues. Biological clocks measure levels of DNA methylation – molecular changes that can indicate an increased risk of morbidity and mortality. These clocks are widely used in the field of aging research.

In all analyses, the researchers saw indications that biological age increased in situations of severe physiological stress, but was restored when the stressful situation resolved itself. In the analysis of patients undergoing major surgery, the team found that signs of biological age increased in patients undergoing emergency surgery to repair a hip fracture, but returned to baseline four to seven days after surgery. This trend was not observed in patients who underwent other non-traumatic surgeries.

In studies of the effect of pregnancy on biological age, researchers observed a consistent trend in humans and mice: biological age increased during pregnancy, up to the time of delivery. This change peaked at the time of delivery and resolved after delivery.

Among patients hospitalized with COVID-19, the team found an increase in biological age that was partially reversed upon discharge from the ICU for female patients. But the team did not see any significant change in the male patients.

The authors note that the clocks they use are biomarkers – signs that may reflect biological age or could be driven by other factors that have not yet been identified. They also note that not all subjects recover their biological age at the same rate or to the same extent – ​​understanding how and why biological age increases and how to improve recovery will be important areas for future studies. But the work indicates a new understanding of the nature of biological aging, with implications for the study of anti-aging interventions.

“Our findings challenge the concept that biological age can only increase over a person’s lifetime and suggest that it may be possible to identify interventions that may slow or even partially reverse biological age,” said lead author Vadim Gladyshev of Brigham’s Division of Genetics. “When stress was relieved, biological age could be restored. This means finding ways to help the body recover from stress could increase longevity.

Funding: This study was funded by the National Institute on Aging, the BWH Organ Design and Engineering Training Program, and the National Institute of Biomedical Imaging and Bioengineering (5T32EB016652-07).