0120 Long-Term Insomnia Burden and Inflammaging and Immunosenescence in Older Adults

Insomnia is common in older adults and has been linked to multiple diseases, yet its underlying biological pathways remain unclear. Emerging evidence suggests that inflammation and immune system dysregulation play important roles in chronic disease. Therefore, we examined the associations between repeated measures of insomnia burden and biomarkers of inflammaging and immunosenescence.We studied 9,709 participants (age=69.34±9.86 years, 58.7% females, 35.2% non-white) from the Health and Retirement Study (HRS). Insomnia symptoms were assessed biennially from 2002 to 2016 using the adapted Jenkins Sleep Scale. Chronic insomnia burden was defined as the cumulative average Jenkins score (sum of scores/number of interviews). We studied 16 blood-based biomarkers measured in the 2016 HRS Venous Blood Study from three domains: inflammation (CRP, IL-6, MLR, NLR, albumin, TNFR1), immune state (CD8+/CD4+ ratio, CD4+ EMRA/naïve ratio, CD8+ EMRA/naïve ratio, memory/naïve T-cell ratio, memory/naïve B-cell ratio, NK cells low-to-high ratio, CMV+ IgG count), and dual-function (i.e., both inflammatory and immune) cytokines (IL-10, TGF-β1, IL-1RA). We used linear regression to estimate associations between chronic insomnia burden and biomarkers, adjusting for age, sex, race, education, APOE ε4, BMI, smoking, alcohol use, physical activity, interview start time, and number of interviews.Higher chronic insomnia symptom burden was consistently associated with higher levels of pro-inflammatory and pro-immune aging biomarkers and lower levels of anti-inflammaging and anti-immune aging biomarkers across inflammation, immune state, and dual-function cytokine domains. Specifically, chronic insomnia burden was associated with higher IL-6, TNFR1, CD8+/CD4+ ratio, CD4+ EMRA/naïve ratio, memory/naïve T-cell ratio, IL-10, and IL-1RA, and with lower albumin and TGF-β1. After further adjustment for baseline chronic diseases, only the associations with two immune-state biomarkers remained: CD4+ EMRA/naïve ratio (B = 0.02 SD, 95% CI: 0.01–0.03) and memory/naïve T-cell ratio (B = 0.01 SD, 95% CI: 0.00–0.02).Chronic insomnia symptom burden was associated with biomarkers of adaptive immunosenescence even after accounting for comorbidities, whereas links with systemic inflammatory markers were largely comorbidity-driven, suggesting immunosenescence as a potential pathway connecting chronic insomnia with later-life health outcomes.National Institute on Aging (R01AG079391, K01AG061239).