Enhanced Molecular Aging in Late-Life Depression: the Senescent-Associated Secretory Phenotype. Am J Geriatr Psychiatry 2017 Jan;25(1):64-72
Date
11/20/2016Pubmed ID
27856124Pubmed Central ID
PMC5164865DOI
10.1016/j.jagp.2016.08.018Scopus ID
2-s2.0-85003955410 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
OBJECTIVE: 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.
DESIGN: Cross-sectional study.
PARTICIPANTS: We included 111 older adults (80 with LLD and 31 comparison participants) in this study.
MEASUREMENT: A 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.
RESULTS: Participants 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).
CONCLUSIONS: To 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.
Author List
Diniz BS, Reynolds CF 3rd, Sibille E, Lin CW, Tseng G, Lotrich F, Aizenstein HJ, Butters MAAuthor
Chien-Wei Lin PhD Associate Professor in the Data Science Institute department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgingCellular Senescence
Cognitive Dysfunction
Cross-Sectional Studies
Depression
Humans
Magnetic Resonance Imaging
Phenotype
White Matter