Enhanced Molecular Aging in Late-Life Depression: the Senescent-Associated Secretory Phenotype

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• 作者：Breno Satler Diniz ; M.D. ; Ph.D.^a ; ^{brenosatler@gmail.com} ; Charles F. Reynolds III ; M.D.^d ; Etienne Sibille ; Ph.D.^c ; Chien-Wei Lin ; Ph.D.^b ; George Tseng ; Ph.D.^b ; Francis Lotrich ; M.D. ; Ph.D.^d ; Howard J. Aizenstein ; M.D. ; Ph.D.^d ; Meryl A. Butters ; Ph.D.^d
• 关键词：late-life depression ; aging ; senescent associated secretory phenotype ; cognitive performance
• 刊名：The American Journal of Geriatric Psychiatry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：25
• 期：1
• 页码：64-72
• 全文大小：490 K
• 卷排序：25

文摘

This study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype [SASP]) is elevated in adults with late-life depression (LLD), compared with never-depressed elderly comparison participants.DesignCross-sectional study.ParticipantsWe included 111 older adults (80 with LLD and 31 comparison participants) in this study.MeasurementA panel of 22 SASP-related proteins was extracted from a previous multiplex protein panel performed in these participants. We conducted a principal component analysis to create the SASP index based on individual weights of each of protein.ResultsParticipants with LLD showed a significantly increased SASP index compared with comparison participants, after controlling for age, depressive symptoms, medical comorbidity (CIRS-G) scores, sex, and cognitive performance (F(1,98) = 7.3, p = 0.008). Correlation analyses revealed that the SASP index was positively correlated with age (r = 0.2, p = 0.03) and CIRS score (r = 0.27, p = 0.005), and negatively correlated with information processing speed (r = −0.34, p = 0.001), executive function (r = −0.27, p = 0.004) and global cognitive performance (r = −0.28, p = 0.007).ConclusionsTo the best of our knowledge, this is the first study to show that a set of proteins (i.e., SASP index) primarily associated with cellular aging is abnormally regulated and elevated in LLD. These results suggest that individuals with LLD display enhanced aging-related molecular patterns that are associated with higher medical comorbidity and worse cognitive function. Finally, we provide a set of proteins that can serve as potential therapeutic targets and biomarkers to monitor the effects of therapeutic or preventative interventions in LLD.