Social regulation of gene expression in human leukocytes
Steve W. Cole,Louise C. Hawkley,Jesusa M.G. Arevalo,Caroline Y. Sung,Robert M. Rose,John T. Cacioppo +5 more
TLDR
In this article, the authors analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates.Abstract:
Background: Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates. Results: DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-κB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and antiinflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/ EBP, Oct, and GATA pathways. Conclusion: These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.read more
Citations
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Loneliness Matters: A Theoretical and Empirical Review of Consequences and Mechanisms
TL;DR: The features and consequences of loneliness are reviewed within a comprehensive theoretical framework that informs interventions to reduce loneliness and features of a loneliness regulatory loop are employed to explain cognitive, behavioral, and physiological consequences.
Journal ArticleDOI
Social isolation, loneliness, and all-cause mortality in older men and women
TL;DR: It was found that mortality was higher among more socially isolated and more lonely participants, and the effect of loneliness was not independent of demographic characteristics or health problems and did not contribute to the risk associated with social isolation.
Journal ArticleDOI
Psychological Stress in Childhood and Susceptibility to the Chronic Diseases of Aging: Moving toward a Model of Behavioral and Biological Mechanisms.
TL;DR: A biological embedding model is presented that maintains that childhood stress gets "programmed" into macrophages through epigenetic markings, posttranslational modifications, and tissue remodeling, and proposes that over the life course, these proinflammatory tendencies are exacerbated by behavioral proclivities and hormonal dysregulation, themselves the products of exposure to early stress.
Journal ArticleDOI
From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression
TL;DR: A biologically plausible, multilevel theory is proposed that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis and may shed light on several important questions including how depression develops, why it frequently recurs, and why it is strongly predicted by early life stress.
Journal ArticleDOI
Perceived social isolation and cognition
TL;DR: Differences in attention and cognition impact on emotions, decisions, behaviors and interpersonal interactions that can contribute to the association between loneliness and cognitive decline and betweenoneliness and morbidity more generally.
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