Summary: Stress can cause rapid and transient increases in biological age, which can be reversed upon recovery, according to a new study. Using DNA methylation clocks, the researchers found that stress triggers short-term fluctuations in biological age in humans and mice. The findings challenge the notion that biological age has a one-way upward trajectory across the life span and underscore the importance of reducing biological age to improve longevity.
Source: Cell phone press
The biological age of humans and mice undergoes a rapid increase in response to different forms of stress, which reverses after recovery from the stress, according to a study published April 21 in the journalcellular metabolism.
These changes occur over relatively short time periods of days or months, according to multiple independent epigenetic aging clocks.
This finding of a fluid, fluctuating, and malleable age challenges the long-held notion of a one-way upward trajectory of biological age across the lifespan, says study co-author James White of Duke University School of Medicine.
Previous reports have hinted at the possibility of short-term fluctuations in biological age, but the question of whether such changes are reversible has, until now, remained unexplored. Critically, the triggers for those changes were also unknown.
It is thought that the biological age of organisms increases steadily throughout life, but it is now clear that biological age is not indelibly linked to chronological age. Individuals may be biologically older or younger than their chronological age implies.
Additionally, growing evidence in animal models and humans indicates that biological age can be influenced by disease, drug treatments, lifestyle changes, and environmental exposures, among other factors.
Despite widespread recognition that biological age is at least somewhat malleable, the extent to which biological age undergoes reversible changes over the course of a lifetime and the events that trigger those changes remain unknown, says study co-author Vadim Gladyshev of Brigham and Womens Hospital, Harvard Medical School.
To address this knowledge gap, researchers harnessed the power of DNA methylation clocks, which were innovated based on the observation that methylation levels at various sites throughout the genome change predictably over the course of age. chronological.
They measured changes in biological age in humans and mice in response to various stressful stimuli. In one set of experiments, researchers surgically attached pairs of 3-month-old and 20-month-old mice in a procedure known as heterochronic parabiosis.
The results revealed that biological age can increase over relatively short periods of time in response to stress, but this increase is transient and tends to drift back towards baseline after recovery from stress. At the epigenetic, transcriptomic, and metabolomic levels, the biological age of juvenile mice was increased by heterochronic parabiosis and restored after surgical detachment.
An increase in biological age following exposure to aged blood is consistent with previous reports of harmful age-related changes following heterochronic blood exchange procedures, says first author Jesse Poganik of Brigham and Women’s Hospital, Harvard Medical School.
However, the reversibility of these changes, as we have observed, has not yet been reported. From this initial insight, we hypothesized that other natural situations could also trigger reversible changes in biological age.
As expected, transient changes in biological age also occurred during major surgery, pregnancy, and severe COVID-19 in humans or mice. For example, trauma patients have experienced a large and rapid increase in biological age following emergency surgery. However, this increase was reversed and biological age was reset to baseline in the days following surgery.
Similarly, pregnant subjects experienced postpartum recovery of biological age at varying rates and extents, and an immunosuppressant drug called tocilizumab improved the recovery of biological age of convalescent COVID-19 patients.
The findings imply that severe stress increases mortality, at least in part, by increasing biological age, Gladyshev says.
This notion immediately suggests that mortality can be reduced by reducing biological age and that the ability to recover from stress may be a major determinant of successful aging and longevity. Finally, biological age can be a useful parameter for assessing physiological stress and its relief.
Further findings showed that second-generation human DNA methylation clocks provide consistent results, whereas first-generation clocks generally lack the sensitivity to detect transient changes in biological age.
Whatever the underlying reason, these data highlight the critical importance of judiciously selecting the appropriate DNA methylation clocks for ongoing analysis, especially in light of the many clocks that continually come to the fore, Gladyshev says.
While this study highlights a previously unappreciated aspect of the nature of biological aging, the researchers acknowledge some important limitations.
Although they characterized the multilevel omics model of parabiosis, they relied primarily on DNA methylation clocks to infer biological age in human studies because these tools are the most powerful biomarkers of aging currently available.
Furthermore, the results are limited in their ability to probe connections between short-term fluctuations in biological age and lifelong biological aging trajectories.
Our study uncovers a new level of aging dynamics that should be considered in future studies, says White. A key area for further investigation is understanding how transient increases in biological age or successful recovery from such increases may contribute to accelerated aging across the life course.
Summary written with the assistance of ChatGPT AI technology
About this news about aging and stress research
Author: Kristopher Benke
Source: Cell phone press
Contact: Kristopher Benke – Cell Press
Image: Image is public domain
Original research: Free access.
“Biological age increased by stress and reset after recovery” by James White et al. cellular metabolism
Biological age is increased by stress and restored after recovery
- Biological age fluctuates rapidly in mice and humans
- Severe stress induces increases in biological age that reverse upon recovery
- Parabiosis, surgery, pregnancy and COVID-19 transiently elevate biological age
- Biological age recovery rate may predict gerotherapy
Aging is classically conceptualized as an ever-increasing trajectory of accumulation of damage and loss of function, leading to increased morbidity and mortality. However, recentin vitrostudies have raised the possibility of age reversal.
Here, we report that biological age is fluid and shows rapid changes in both directions. At the epigenetic, transcriptomic and metabolomic levels, we find that the biological age of young mice is increased by heterochronic parabiosis and restored after surgical detachment.
We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to different forms of stress, which reverses after recovery from stress.
Our study uncovers a new level of aging dynamics that should be considered in future studies. Elevation of biological age due to stress may be a quantifiable and actionable goal for future interventions.