Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine

•What is the primary question addressed by this study? We sought to evaluate the circulating levels of growth differentiation factor-15 (GDF-15) in older adults with major depressive disorder and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance.•What is the main finding of this study? Depressed older adults had significantly higher GDF-15 serum levels than comparison individuals. Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression.•What is the meaning of the finding? GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging. In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance. This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals. After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression. Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging.