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Karin de Punder, PhD, a postdoctoral researcher at the University of Innsbruck, Innsbruck, Austria, has conducted research on how chronic stress accelerates the aging of the immune system and its connection to depression. Traditionally, depression has been diagnosed on the basis of self-reported symptoms; however, reliable clinical biomarkers are lacking.

de Punder and colleagues have explored new potential biomarkers in ongoing studies. She recently presented her findings at the German Congress for Psychosomatic Medicine and Psychotherapy in Berlin from March 12 to 14, 2025, during a session titled “Stress and Aging: A Biological Basis of Trauma and Depression Symptoms?”

de Punder stated, “Chronic stress affects the immune system by accelerating its aging,” highlighting the important implications of the study.

The molecular toxic properties of chronic stress promote these processes, including:

• Changes in stress reactivity, such as decreased sensitivity of cortisol receptors.
• Increased inflammation, particularly low-grade inflammation caused by chronic overactivity of the innate immune system, particularly when trauma is experienced early in life.
• Oxidative stress results in increased free radical production due to inflammation, which damages cells.
• Reduced mitochondrial function leads to less energy available for the repair and regeneration processes.
• Accelerated telomere shortening due to increased oxidative stress and inflammation.

Shortened Telomeres

Telomeres, which are the protective caps of chromosomes, shorten during cell division. Stress accelerates this process. When the telomere length falls below a critical threshold, cell death and senescence occur. Senescent cells cannot divide but continue to secrete pro-inflammatory signaling molecules. Accelerated telomere shortening has been linked to a shorter lifespan and various diseases, including coronary artery disease, atherosclerosis, type 2 diabetes, autoimmune diseases, and mental disorders, such as depression.

Depression Biomarkers

In studies examining how stress contributes to disease risk, researchers often measure the telomere length in peripheral blood mononuclear cells.

If leukocyte aging and telomere length are associated with depression, they could serve as potential biomarkers, aiding the identification of depression through physical parameters.

To identify these biomarkers, researchers analyzed blood samples from 22 patients diagnosed with depression, all of whom received inpatient treatment. Age-matched women without depression, with an average age of 58 years, served as controls. The severity of depression was measured using the Beck Depression Inventory II, and traumatic stress was assessed using the Essen Trauma Inventory.

Blood samples were isolated to measure telomere length, and serum was used for mass spectrometry–based omics analysis to generate the biochemical profiles. In total, 682 metabolites were identified and evaluated for their association with depression and telomere length.

Further investigation focused on glyceraldehyde, revealing that blood levels were significantly correlated with the severity of depression and trauma and with the inflammatory marker C-reactive protein, which is often elevated in patients with depression. Notably, higher glyceraldehyde levels were associated with shorter telomeres, particularly in CD8+ cells. These findings remained significant even after adjusting for age and body mass index.

Glyceraldehyde and Depression

Glyceraldehyde is a triose monosaccharide and an intermediate in carbohydrate metabolism. This highly reactive molecule can modify and bind proteins, resulting in the formation of advanced glycation end products. Glyceraldehyde-modified proteins exert cytotoxic effects by reducing glutathione levels, which protects cells from damage and leads to the production of reactive oxygen species, thereby promoting inflammatory responses.

“These are precisely the processes that negatively affect telomere length,” said de Punder.

Glyceraldehyde, with other markers, could serve as a biomarker for a subtype of depression linked to immune system activation.

The study also suggested that a slightly elevated C-reactive protein level above 1 mg/L may not always indicate infection but could reflect low-grade chronic inflammation.

“This would give physicians a testing option to determine whether this form of depression is present,” said de Punder.

To validate these results, the study requires duplication in a larger cohort with a longitudinal design, a broader age range, and inclusion of both sexes. Further investigations are needed to better understand the mechanisms linking glyceraldehyde to depression, trauma, and telomere biology.

“If we have multiple biomarkers available in the future, we can not only improve the detection of depressive disorders but also better tailor treatment,” de Punder emphasized.

This story was translated from Medscape’s German edition.