Interactions Between Biological Aging and Psychopathology

Anthony Zannas recently published a provocative JAMA Psychiatry commentary entitled “Biological Aging and Mental Illness, A Vicious Cycle?” The concepts presented in this article are important to consider.

Biologic aging versus chronologic aging

The body may age faster or slower than predicted from a person’s chronologic age. The pace of biological aging is influenced by many stressors, which affect lifespan. Biological age can be determined from a blood sample by measuring chemical changes associated with DNA.

Relationships between biological aging and psychopathology

It is known that persons with certain psychiatric illnesses die years earlier on average than those without such disorders. These illnesses may be associated with inflammation, cellular and mitochondrial stress, structural changes in brain tissue, and or neuroendocrine changes. Such changes may be responsible for more rapid biological aging and lead to premature death.

In addition to psychiatric disorders being associated with more rapid biological aging, Zannas discusses evidence that more rapid biological aging increases the risk of developing psychopathology. In a 2023 paper in Psychological Medicine, Zannas and colleagues demonstrated a relationship between biological aging and the development of post-traumatic stress disorder (PTSD) following a traumatic event. In this study, the authors measured the difference between biological age and chronological age in persons who presented at an emergency room following a major traumatic event.

They subsequently followed these individuals for six months to determine how many developed PTSD. Study participants were divided into three groups: the third with the largest difference between biological age and chronological age (that is, those who biologically were aging the most rapidly); those in the middle third; and those with the smallest difference between biological age and chronological age. Individuals in the most rapidly aging group were 17 percent more likely to develop PTSD six months following the traumatic event than those in the middle group, and 44 percent more likely than those in the lowest group. In other words, those who were biologically aging the fastest were much more likely to develop PTSD following a traumatic event than those who were aging the slowest.

A similar conclusion was reached by Xu Gao and colleagues in a 2023 paper published in the journal Nature Communications. These investigators demonstrated an increased risk of developing depression and anxiety in individuals who had the greatest difference between biological age and chronological age.

From such data, Zannas suggests that the relationship between biological aging and mental illness is bidirectional, that is, faster biological aging is associated with increased development of mental illnesses and the development of mental illnesses can accelerate biological aging.

Implications

This bidirectional relationship between aging and psychopathology has several therapeutic implications. First, measuring the difference between biological age and chronological age in someone experiencing a major psychological stressor may provide information about the risk of that person developing PTSD. Those at high risk would likely benefit from preventative interventions. Second, behaviors and treatments that slow biological aging may decrease the risk of developing certain mental disorders. Third, the prevention or successful treatment of mental disorders may help slow biological aging.

Currently, lifestyle modifications such as exercise, stress reduction, and a healthy diet may be beneficial in both decelerating biological aging and diminishing the risk of developing certain mental illnesses. Elucidating the mechanisms underlying the relationships between biological aging and psychopathology may lead to better preventative strategies.

This column was written by Eugene Rubin MD, PhD, and Charles Zorumski MD.