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

• Published in: The American journal of geriatric psychiatry Vol. 25; no. 1; p. 64
• Main Authors: Diniz, Breno Satler, Reynolds, 3rd, Charles F, Sibille, Etienne, Lin, Chien-Wei, Tseng, George, Lotrich, Francis, Aizenstein, Howard J, Butters, Meryl A
• Format: Journal Article
• Language: English
• Published: England 01.01.2017
• Subjects: Aging - metabolism; Cellular Senescence - physiology; Cognitive Dysfunction - physiopathology; Cross-Sectional Studies; Depression - metabolism; Humans; Magnetic Resonance Imaging; Phenotype; White Matter - diagnostic imaging; senescent associated secretory phenotype; late-life depression; aging; cognitive performance
• ISSN: 1545-7214
• DOI: 10.1016/j.jagp.2016.08.018

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. Cross-sectional study. We included 111 older adults (80 with LLD and 31 comparison participants) in this study. 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. 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  = 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). 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.