Sleep disturbance and activation of cellular and transcriptional mechanisms of inflammation in older adults.

ABSTRACT

BACKGROUND: Sleep disturbance, including poor subjective sleep quality and insomnia disorder, is common in older adults and associated with increases in age-related morbidity risk. Accumulating evidence implicates inflammation as an underlying mechanism. In two complementary studies, we examined whether sleep disturbance is associated with activation of cellular and transcriptional mechanisms of inflammation in older adults. METHODS: Study 1 examined whether healthy older adults with poor subjective sleep quality (n = 62), compared to those with good subjective sleep quality (n = 101), differed in monocytic production of interleukin (IL)-6 and/or tumor necrosis factor (TNF)-α following stimulation with lipopolysaccharide. Study 2 examined whether older adults with insomnia disorder (n = 17), compared to those without insomnia disorder (n = 25), differed in the regulation of transcription factors (TFs) related to immune activation (i.e., nuclear factor-κB/Rel family), sympathetic nervous system (SNS) activity (i.e., cAMP-response element-binding protein), hypothalamic-pituitary-adrenal (HPA) axis activity (i.e., glucocorticoid receptor) and anti-viral responses (i.e., interferon-regulatory factor/interferon-stimulated response element) assessed in peripheral blood mononuclear cells. RESULTS: In Study 1, older adults with poor subjective sleep quality, compared to those with good subjective sleep quality, showed higher percentages of stimulated monocytes producing IL-6 only (25.4 ± 16.8 % vs 20.4 ± 13.9 %; p < 0.05, ηp2 = 0.03), producing TNF-α only (37.6 ± 13.1 % vs 31.2 ± 14.3 %; p < 0.01, ηp2 = 0.05), and co-producing IL-6/TNF-α simultaneously (17.8 ± 11.7 % vs 13.9 ± 9.6 %; p < 0.05, ηp2 = 0.03). In Study 2, older adults with insomnia disorder, compared to those without insomnia disorder, showed higher TF activity related to immune activation (p's < 0.05) and SNS function (p's < 0.001), along with lower TF activity related to HPA axis function (p's < 0.05). CONCLUSION: In older adults, poor subjective sleep quality and insomnia diagnosis are associated with increases in monocytic cytokine production and changes in TF activity related to immune activation, SNS function, and HPA axis function. Activation of markers of cellular and transcriptional inflammation might contribute to the link between sleep disturbance and age-related morbidity risk.