Sleep Maintenance Insomnia in Older Adults: Cardiometabolic Comorbidities and Evidence of Antiviral Pathways Activation from Blood Transcriptome and dsRNA Expression Analyses

TL;DR

Older adults with sleep maintenance insomnia show signs of antiviral immune activation and cardiometabolic issues in blood gene expression.

Contribution

This study reveals antiviral pathway activation in sleep maintenance insomnia through transcriptomic and dsRNA analysis.

Findings

244 genes were differentially expressed in middle insomnia, linked to antiviral response and protein synthesis inhibition.

2139 significant dsRNA expression changes were found in middle insomnia patients.

Middle insomnia is associated with cardiometabolic diseases and chronic inflammation from transcriptomic alterations.

Abstract

Aging is associated with a high prevalence of insomnia, which is linked to somatic and neuropsychiatric diseases, as well as metabolic and immunological dysfunction. This study aims to identify alterations in the transcriptome profiles and functional metabolic pathways in older adults with different types of sleep disorders. This cross-sectional study included 1002 participants (60–90 years) who were screened for sleep disorders using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Two types of sleep disorders were identified in the study cohort, i.e., sleep onset insomnia and sleep maintenance insomnia. Both types of insomnia were further analyzed for associations with clinical characteristics, laboratory testing results, and socioeconomic backgrounds. The transcriptomic profiles of peripheral blood samples were examined in 236 individuals, supplemented with differential gene and dsRNA expression analyses (DESeq2). Both sleep onset insomnia and middle insomnia were associated with depression, chronic pain syndrome, and osteoarthritis, while only middle insomnia was associated with cardiometabolic diseases. No associations were observed between sleep onset insomnia or reduced sleep duration and transcriptomic profiles. In contrast, 244 genes were differentially expressed in patients with middle insomnia, indicating the activation of pathways related to viral infection response and inhibition of protein synthesis. Additionally, differential expression analysis of double-stranded RNA (dsRNA) identified 2139 significant changes. Middle insomnia in older adults is associated with transcriptomic changes indicative of an activated antiviral immune response, likely resulting from changes in dsRNA expression levels. The chronic inflammation arising from these transcriptomic alterations may underlie the observed association between middle insomnia and cardiometabolic conditions.

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