TY - JOUR
T1 - Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine
AU - Mastrobattista, Emma
AU - Lenze, Eric J.
AU - Reynolds, Charles F.
AU - Mulsant, Benoit H.
AU - Wetherell, Julie
AU - Wu, Gregory F.
AU - Blumberger, Daniel M.
AU - Karp, Jordan F.
AU - Butters, Meryl A.
AU - Mendes-Silva, Ana Paula
AU - Vieira, Erica L.
AU - Tseng, George
AU - Diniz, Breno S.
N1 - Publisher Copyright:
© 2022 American Association for Geriatric Psychiatry
PY - 2023/1
Y1 - 2023/1
N2 - Objective: 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. Design: 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. Results: 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. Conclusion: 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.
AB - Objective: 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. Design: 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. Results: 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. Conclusion: 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.
KW - Aging
KW - GDF-15
KW - Geroscience
KW - Late life depression
KW - biological markers
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U2 - 10.1016/j.jagp.2022.08.003
DO - 10.1016/j.jagp.2022.08.003
M3 - Article
C2 - 36153290
AN - SCOPUS:85138808244
SN - 1064-7481
VL - 31
SP - 1
EP - 9
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 1
ER -