Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life

Abstract

Objective: Late-life depression (LLD) is a chronic and heterogeneous disorder. Recent studies have implicated non-normative age-related processes in its pathogenesis. This investigation examined both cross-sectional and longitudinal associations between skeletal muscle mitochondrial function and LLD. Methods: Data from 603 men and women from the Baltimore Longitudinal Study on Aging were analyzed, of whom 167 provided data from a follow-up visit. Muscle bioenergetics was measured by postexercise recovery rate of phosphocreatine (PCr) using phosphorus magnetic resonance spectroscopy. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Results: There was no cross-sectional association between baseline depression status and either the PCr recovery rate constant (kPCr; t= −0.553, df=542; p = 0.580) or mitochondrial capacity largely independent of exercise intensity (adenosine triphosphate maximum [ATP max ]; t = 0.804, df=553; p = 0.422). Covariate-adjusted Firth logistic regression models however showed that greater decreases in skeletal muscle mitochondrial function from baseline to follow-up were associated with higher odds of clinically significant depressive symptoms (CES-D 16) at follow-up (ΔATP max : odds ratio = 2.63, χ 2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ 2 =5.79, df =1; p = 0.016). Conclusion: Findings suggest that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up, thereby providing preliminary support for the hypothesis that mitochondrial dysfunction may be a

Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature

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Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

“…They are associated with cognitive impairment, physical comorbidity burden, and higher mortality risk. 10 , 11 , 12 , 13 , 14 , 15 Cellular senescence and changes in its cellular secretome (ie, the senescence-associated secretory phenotype or SASP) are other important hallmarks of biological aging. 16 The SASP factors comprise several signaling proteins associated with inflammatory control, tissue remodeling, cell growth, cell cycle control, and metabolic regulation.…”

Physical exercise and mitochondrial function: New therapeutic interventions for psychiatric and neurodegenerative disorders

“…. function in aging adults was also shown to be associated with clinically significant depressive symptoms (66). These lines of evidence support the critical regulatory roles of mitochondria in antidepressant functions.…”

“…They observed that LRs displayed higher cytochrome c oxidase (COX) activity in the dentate gyrus, prefrontal cortex, and dorsal raphe compared to HRs ( 65 ). Apart from selected brain regions, a declining skeletal muscle mitochondrial function in aging adults was also shown to be associated with clinically significant depressive symptoms ( 66 ). These lines of evidence support the critical regulatory roles of mitochondria in antidepressant functions.…”