Depressed people age more quickly

As many of you know, we are partnering with the University of Queensland in the Longevity project. The aim is to find ways to increase the active longevity of people in Australia. Our findings and our discoveries will bring benefits in the quest for a cognitively and physically more active old age throughout the world.

This is one of the reasons that I often include research on aspects of aging in TR. This study is one of the more significant ones to appear in the last few weeks. We have known for a long time that depression, especially what is known as major depressive disorder (MDD, which is just about as bad as it gets), is responsible for a number of physical disorders including heart disease, cancer and diabetes.

Now we find that it might have even more pernicious effects which are very relevant to the issue of longevity.

The researchers found that cells from individuals with MDD had higher than expected rates of methylation at specific sites on their DNA, when compared to cells from healthy individuals without MDD. As TR readers may remember from previous studies, methylation is a process by which DNA is chemically modified at specific sites, resulting in changes in the expression of certain genes.

Methylation of particular sets of genes, called “DNA methylation clocks,” typically change in predictable ways as people age, but the rate of these changes varies between people. Methylation patterns in individuals with MDD suggested that their cellular age was, on average, accelerated relative to healthy controls.

In the study, published in Translational Psychiatry, blood samples from individuals with MDD were analyzed for methylation patterns using a mathematical algorithm designed to predict an individual’s remaining lifespan based on cellular methylation patterns. Individuals with MDD showed a significantly higher score, suggesting two years shorter lifespan.

Those with MDD showed no outward signs of age-related pathology, as they and the healthy controls were screened for physical health before entry into the study. The methylation patterns associated with mortality risk persisted even after accounting for lifestyle factors like smoking and BMI. These findings provide new insight into a probable underlying biological mechanism accelerating cellular aging in some MDD sufferers.

What the researchers say: “This is shifting the way we understand depression, from a purely mental or psychiatric disease, limited to processes in the brain, to a whole-body disease,” said the lead author of the study. “This should fundamentally alter the way we approach depression and how we think about it—as a part of overall health.”

MDD is one of the most prevalent health concerns globally, and rapidly increasing. It is associated with higher incidence and mortality related to heightened rates of cardiovascular disease, diabetes, and Alzheimer’s disease among sufferers.

“One of the things that’s remarkable about depression is that sufferers have unexpectedly higher rates of age-related physical illnesses and early mortality, even after accounting for things like suicide and lifestyle habits,” said the study’ co-author. “That’s always been a mystery, and that’s what led us to look for signs of aging at the cellular level.”

The researchers collected blood samples from 49 individuals with MDD who were unmedicated prior to the study and 60 healthy control subjects of the same chronological age. They analyzed the methylation rates of both groups using the algorithm.

The researchers say that they don’t yet know if depression causes altered methylation in certain individuals, or if depression and methylation are both related to another underlying factor. It is possible that some individuals may have a genetic predisposition to produce specific methylation patterns in response to stressors, but this has not been well-studied. Alterations in methylation patterns have previously been observed in individuals with Post-Traumatic Stress Disorder.

Moving forward, the researchers hope to determine whether pharmacological treatments or therapy may mitigate some methylation changes related to MDD in hopes of normalizing the cellular aging process in affected individuals before it advances.

“As we continue our studies, we hope to find out whether addressing the MDD with anti-depressants or other treatments alters the methylation patterns, which would give us some indication that these patterns are dynamic and can be changed,” said the researchers.

So, what? The problem is that there is no clear understanding of what causes what. The genes that predispose people to depression are what are known as “soft genes.” This means that they are easily influenced by context (especially relational context) and experience.

Stress—especially work stress—is a prime factor in this genetic influencing. It has also been shown to be a prime cause of depression and other mental health issues. This kind of stress was increasing at the rate of 70% every four years pre-COVID and so we must expect that the incidence of accelerated aging is also increasing.