Chronic Stress Accelerates Aging: Epigenetic Evidence

Mauricio Wajngarten, MD

February 03, 2022

The increase in cardiovascular disease caused by chronic stress is related to biologic mechanisms (metabolic, hormonal, inflammatory) and to behavioral mechanisms (lifestyle). There is a popular saying that "stress speeds up aging," which makes sense if we consider the age-old idea that "our age corresponds to that of our arteries."

The study of the mechanisms of psychosocial risk factors is of major relevance to the creation of the individual and communal preventive strategies that ensure longevity and maintain quality of life.

The following hypotheses were proposed by a group of researchers from Yale University, in New Haven, Connecticut, in a recent study:

1.    Stress is positively associated with accelerated biologic aging, and this relationship will be mediated by stress-related physiologic changes, such as insulin and hypothalamo-pituitary-adrenal (HPA) signaling.

2.    Strong factors associated with psychologic resilience will be protective against the negative consequences of stress on aging. (These relationships are predictive, not causative, as this study is cross-sectional.)

The Study

In their study, the team assessed 444 adults with no chronic medical conditions or psychiatric disorders who were 18 to 50 years of age and living in the greater New Haven area. Levels of obesity and alcohol consumption in the study cohort were generally in line with those in a community population, so alcohol use and body mass index were used as covariates to account for their impact on the results.

The team also used the latest "epigenetic clock," known as GrimAge. In recent years, several methods of determining biologic age have been developed that trace chemical changes in the DNA that are natural to the aging process but occur at different moments in different people. The epigenetic clocks have proven to be better predictors of longevity and health than chronologic age, and GrimAge predicts mortality better than other epigenetic clock.


1.    Cumulative stress was associated with the acceleration of GrimAge and stress-related physiologic measures of adrenal sensitivity (cortisol/ACTH ratio) and insulin resistance (HOMA). After the researchers controlled for demographic and behavioral factors, HOMA was correlated with GrimAge acceleration.

2.    Psychologic resilience factors moderated the association between stress and aging, such that with worse regulation of emotions, there was greater stress-related age acceleration, and with stronger regulation of emotions, any significant effect of stress on GrimAge was prevented. Self-control moderated the relationship between stress and insulin resistance, with high self-control blunting this relationship.

3.    In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge acceleration, even when demographic, physiologic, and behavioral covariates were accounted for.


These results elegantly demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.

Even after adjustment for demographic and behavioral factors — such as smoking, body mass index, race, and income — people with high chronic stress scores showed markers of accelerated aging and physiologic changes, such as increased insulin resistance.

However, individuals with high scores on two psychologic resilience measures — emotion regulation and self-control — were more resilient to the effects of stress on aging and insulin resistance.

These results support the popular notion that stress ages (and sickens) us, and suggest a viable way of minimizing the adverse consequences of stress by strengthening the regulation of emotion and self-control.

In other words, the greater the psychologic resilience, the more likely the individual is to live a long and healthy life. "We like to feel as if we have some sovereignty over our destiny and, therefore, it is worth emphasizing to people (and healthcare providers) that it is important to invest in mental health," said one of the study researchers.

With all the stress we face these days, it is essential to remember that there is no health without mental health. Above all, if we can achieve greater psychologic resilience, we will have a better chance of delaying aging.

Transl Psychiatry. 2021;11:601. Full text

This article originally appeared in the Portuguese edition of Medscape.

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