biostudies-literatureMastrobattista ENIA NIH HHSNIMH NIH HHS1-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC9701166biostudies-literatureUnknown31(1)<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric PsychiatryLate-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine.PMC9701166R01 MH083660R01 MH118311R01 AG049369Butters MADiniz BSReynolds CFMendes-Silva APMastrobattista ELenze EJVieira ELTseng GWetherell JBlumberger DMKarp JFMulsant BHWu GFfalseLate-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine.<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.2023-01-01T00:00:00Z2023 Jan2026-05-28T01:38:54.698Z2025-04-06T12:28:18.072ZS-EPMC97011663615329010.1016/j.jagp.2022.08.003