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Research Highlights

Stress-induced increases in biological age are reversible

Exposure to stress increased biological age in humans and mice, but it decreased after the stress resolved, according to NIA-funded research. Findings from the study were published in Cell Metabolism.

Image of DNA methylation in orange and blue

Biological age refers to the accumulating damage, physiological changes, and loss of function that occur in a person’s cells over time. One method scientists use to measure biological age examines the epigenome, which contains a record of changes to a cell’s DNA and DNA-associated proteins.

Led by Harvard University scientists, this study used DNA methylation (DNAm)-based aging clocks to measure changes in biological age in response to diverse forms of stress. The researchers began with a laboratory experiment known to produce aged physiology in young mice or restore youthful physiology to old mice by surgically joining young, 3-month-old mice with older, 20-month-old mice, which allowed them to share their blood. At the molecular level, they found that the biological age of the young mice increased when measured with most aging clocks. Once the young mice were separated from the old mice and therefore were no longer experiencing the older mouse physiology, their biological age returned to youthful levels. This finding suggested that biological age is malleable and potentially reversible, and these changes are reported by DNAm aging clocks.

Next, the researchers examined blood samples from people who had recently experienced stressful situations, including surgery (emergency versus elective), pregnancy, or severe COVID-19. Analysis of blood samples from patients who underwent emergency surgery showed their biological age increased the morning after surgery and returned to pre-surgery levels four to seven days later. Elective surgeries, on the other hand, had less impact on biological age, which the authors attribute to pre-operative regimens known to aide recovery. Pregnancy in both mice and humans led to increased biological age at delivery, which reverted to lower biological age following delivery and recovery.

The research team found the same reversible biological age in older adults with severe COVID-19, although the change differed by gender and treatment. The scientists also found people in the group who were treated with the immunosuppressive drug tocilizumab, usually prescribed to treat moderate to severe rheumatoid arthritis, showed a greater reversal of their increased biological age related to COVID-19.

The elevation and subsequent return to baseline of biological age found in this study may represent possible targets for geroscience-based interventions to improve health at older ages. Future research may explore how temporary fluctuations of apparent biological age influence aging over a lifetime.

This research was supported in part by NIA grant R21AG065943.

Reference: Poganik JR, et al. Biological age is increased by stress and restored upon recovery. Cell Metabolism. 2023;35(5):807-820.e5. doi: 10.1016/j.cmet.2023.03.015.

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