Social regulation of gene expression in human leukocytes

By Steve W. Cole, Louise C. Hawkley, Jesusa Arevalo, C. Sung, Robert M. Rose, John T. Cacioppo. Genome Biology, 2007

717 citations recorded by the source corpus.

BackgroundSocial 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.ResultsDNA 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 anti-inflammatory 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.ConclusionThese 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.

Subfields: Behavioral Neuroscience, Health, Immunology

View Paper: https://www.semanticscholar.org/paper/002a5840c98c2ceae1d77a4e1e204bd18a242808

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Citations in the corpus

Loneliness Predicts Increased Blood Pressure: Five-Year Cross-Lagged Analyses in Middle-Aged and Older Adults (2010, background): “…2004), underexpression of genes bearing anti-inflammatory glucocorticoid response elements (GREs), overexpression of genes bearing response elements for proinflammatory NF-#B/Rel transcription factors (Cole et al., 2007), and altered immunity (Kiecolt-Glaser et al., 1984; Pressman et al., 2005).”
Social Relationships and Health: The Toxic Effects of Perceived Social Isolation. (2014, background): “…Ernst, et al., 2000;Hawkley, Thisted, & Cacioppo, 2009); altered gene expression, for instance, increasing inflammatory biology to deal with assaults (Cole et al., 2007, 2011); and the decreased salubriousness of sleep, the consequence of the brain’s high alert state (Cacioppo, Hawkley, Berntson,…”
From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression (2014, background): “…types of social adversity, including being socially isolated or low in social status, or experiencing high levels of chronic interpersonal stress (e.g., Chen et al., 2009; S. W. Cole et al., 2007, 2011; G. E. Miller et al., 2008; G. E. Miller, Rohleder, & Cole, 2009; see also Tung et al., 2012).”
Emotional Experience Improves With Age: Evidence Based on Over 10 Years of Experience Sampling (2011, background): “That is, negative emotional states activate biological systems that influence immune resistance, disease progression, and even gene expression (Cole et al., 2007).”
Perceived Social Isolation Makes Me Sad: Five Year Cross-Lagged Analyses of Loneliness and Depressive Symptomatology in the Chicago Health, Aging, and Social Relations Study (2010, background): “…and depressive symptoms have found them to be distinct conditions statistically (e.g., Bell, 1985; Cacioppo, Hawkley, et al., 2006; Cacioppo, Hughes, et al., 2006; Rook, 1987; Russell, 1996; Weeks et al., 1980) and functionally (e.g., Adam et al., 2006; Cole et al., 2007; Hawkley et al., 2006).”
Hearing Loss and Cognition in the Baltimore Longitudinal Study of Aging (2011, background): “…direct pathophysiologic effects of altered gene expression profiles and increased inflammation in lonely individuals (Cole, Hawkley, Arevalo, & Cacioppo; Cole et al., 2007) or through psychosocial pathways of social support and influence (Berkman, Glass, Brissette, & Seeman, 2000; Uchino, 2006).”
Hearing loss and cognitive decline in older adults: questions and answers (2014, background): “increased inflammation [22, 23]; (b) poorer health behavioral pathways: smoking, adherence to medical treatment, diet, exercise, and (c) psychological pathways: self-esteem, self-efficacy, coping, sense of well-being.”
Stress and Health: A Review of Psychobiological Processes. (2020, background): “This exploration started just over a decade ago with a small study which focused not on stress, but its co-conspirator social isolation (Cole et al., 2007).”
Loneliness Matters: A Theoretical and Empirical Review of Consequences and Mechanisms (2010, neutral): “, perceived stress, depression, hostility), or medical risk factors [75].”
Loneliness: Clinical Import and Interventions (2015, background): “…2005), an underexpression of genes bearing anti-inflammatory glucocorticoid response elements and an upregulation of pro-inflammatory gene transcripts (Cole et al., 2007, 2011), abnormal ratios of circulating white blood cells (e.g., neutrophils, lymphocytes, and monocytes; Cole, 2008), and…”
Positive Emotions Broaden and Build (2012, background): “…linked the increased expression of proinflammatory cytokine genes to various circumstances replete with chronic negative affect such as loneliness (Cole et al., 2007), social stress (Miller et al., 2008; Miller, Rohleder, & Cole, 2009), low socioeconomic status (Chen et al., 2009), and general…”
A Meta-Analysis of Interventions to Reduce Loneliness (2010, background): “…2006), diminished immunity (Kiecolt-Glaser et al., 1984; Pressman et al., 2005), underexpression of genes bearing anti-inflammatory glucocorticoid response elements (Cole et al., 2007), and abnormal ratios of circulating white blood cells (e.g., neutrophils, lymphocytes, and monocytes; Cole, 2008).”
Reciprocal regulation of the neural and innate immune systems (2011, background): “Collectively, these studies of neuro–immune regulation have provided new insights into the mechanistic relationships between the cellular and microbial microenvironment in which immune responses have traditionally been analysed and the broader macroenvironment of the host body and its surrounding so”
Social isolation, loneliness, and all-cause mortality in older men and women (2013, background): “Loneliness itself has been linked with increased risk of cardiovascular disease and mortality (15–18), elevated blood pressure and cortisol (19–21), heightened inflammatory responses to stress (22, 23), and modifications in transcriptional pathways linked with glucocorticoid and inflammatory process”
Loneliness, social isolation, and behavioral and biological health indicators in older adults. (2011, background): “A recent genome-wide study indicated that genes associated with the anti-inflammatory glucocorticoid receptor pathway were underexpressed, while the proinflammatory NF- B/Rel transcription pathway was overexpressed among lonely when compared with nonlonely participants (Cole et al., 2007).”