Department of Geriatrics, Florida State University, Tallahassee, United States; Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, United States
Division of Behavioral Medicine, Department of Psychiatry; Merritt Center and Columbia Translational Neuroscience initiative, Department of Neurology, Columbia University Irving Medical Center; New York State Psychiatric Institute, New York, United States
Yong Qian
Translational Gerontology Branch, National Institute on Aging, Baltimore, United States
Thomas J Butler
Translational Gerontology Branch, National Institute on Aging, Baltimore, United States
Translational Gerontology Branch, National Institute on Aging, Baltimore, United States
Ann Zenobia Moore
Translational Gerontology Branch, National Institute on Aging, Baltimore, United States
Eleanor M Simonsick
Translational Gerontology Branch, National Institute on Aging, Baltimore, United States
Krista Opsahl-Ong
Translational Gerontology Branch, National Institute on Aging, Baltimore, United States
Christopher Coletta
Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, United States
Angelina R Sutin
Department of Behavioral Sciences and Social Medicine, College of Medicine, Florida State University, Tallahassee, United States
Myriam Gorospe
Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, United States
Susan M Resnick
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, United States
Francesco Cucca
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy
Sonja W Scholz
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, United States; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, United States
Bryan J Traynor
Department of Neurology, Johns Hopkins University Medical Center, Baltimore, United States; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, United States
David Schlessinger
Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, United States
Background: Mitochondrial DNA copy number (mtDNAcn) in tissues and blood can be altered in conditions like diabetes and major depression and may play a role in aging and longevity. However, little is known about the association between mtDNAcn and personality traits linked to emotional states, metabolic health, and longevity. This study tests the hypothesis that blood mtDNAcn is related to personality traits and mediates the association between personality and mortality. Methods: We assessed the big five personality domains and facets using the Revised NEO Personality Inventory (NEO-PI-R), assessed depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), estimated mtDNAcn levels from whole-genome sequencing, and tracked mortality in participants from the Baltimore Longitudinal Study of Aging. Results were replicated in the SardiNIA Project. Results: We found that mtDNAcn was negatively associated with the Neuroticism domain and its facets and positively associated with facets from the other four domains. The direction and size of the effects were replicated in the SardiNIA cohort and were robust to adjustment for potential confounders in both samples. Consistent with the Neuroticism finding, higher depressive symptoms were associated with lower mtDNAcn. Finally, mtDNAcn mediated the association between personality and mortality risk. Conclusions: To our knowledge, this is the first study to show a replicable association between mtDNAcn and personality. Furthermore, the results support our hypothesis that mtDNAcn is a biomarker of the biological process that explains part of the association between personality and mortality. Funding: Support for this work was provided by the Intramural Research Program of the National Institute on Aging (Z01-AG000693, Z01-AG000970, and Z01-AG000949) and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. AT was also supported by the National Institute on Aging of the National Institutes of Health Grant R01AG068093.
