A Randomized Trial for Sleep Disturbances to Reverse Cellular Aging
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DESCRIPTION (provided by applicant): Research is needed to bridge the continuum from behavioral factors to molecular stress, define the role of cellular aging in age related rises in inflammation, and identify interventional strategies that may alter the course of aging and ultimately improve the number of healthy years of living. The current proposal seeks to address this need by targeting sleep, a modifiable behavior that has been linked to aging and age related disease. Sleep disturbances elevate risk for chronic disease, possibly by accelerating aging and age related rises in inflammation. No research to date has demonstrated a role of sleep disturbances in these pathways nor tested whether remission of sleep disturbances using highly efficacious behavioral strategies reverses the cellular aging processes. This project will leverage an ongoing randomized clinical trial (RCT; R01 AG026364; Irwin) that is testing whether treatment of sleep disturbance using cognitive behavioral therapy for sleep quality (CBT-SQ) vs. sleep seminar (SS), controls, improves sleep and reduces the risk for depression in non-depressed older adults with sleep complaints (Pittsburgh Sleep Quality Index, PSQI >5; n=305) over a 3-year follow-up with assessments at baseline, 12 months, 18 months, 24 months, 36 months. In this project, we will aim to: 1) evaluate the effects of CBT-SQ vs. SS on markers of cellular aging over 3-years. Hypothesis 1: Relative to SS, CBT-SQ for sleep disturbances will improve mitochondrial function, increase telomerase activity, lengthen PBMC telomeres, and reduce expression of key aging related genes over 3-years. 2) Evaluate the effects of sleep disturbance remission (PSQI <5) at 6 months vs. unremitted sleep disturbance on markers of cellular aging over 3 years follow-up. Hypothesis 2: Relative to remitters, those with unremitting sleep disturbances (PSQI Global >5) at 6 months will show poorer mitochondrial function, lower telomerase, shorter PBMC telomeres, and greater expression of key aging related genes over 3-years. Exploratory Aim: To address critical gaps in current knowledge, we will apply discovery science approaches using advanced bioinformatics methods to interpret whole genome gene expression arrays and age related epigenetic methylation patterns to DNA to provide novel understanding in the role of sleep disturbances to cellular biology. In addition, we will use existing inflammatory data collected from the parent R01 to examine a possible bi- directional relationship between cellular aging and inflammation (i.e., inflammaging). Impact Statement: The proposed project addresses a very significant issue in the field of biobehavioral sleep research as it will be the first study to examine whether treatment of sleep disturbances reverses processes of cellular aging, using numerous innovative molecular biomarkers of this process over 3 years, and leveraging a well powered and demonstrated RCT to treat sleep disturbances. This work has the potential to implicate late life sleep disturbances in the progression of biological aging, and to demonstrate that interventions to treat sleep disturbances in older adults may slow or even reversing cellular aging.
