Remission of insomnia in older adults treated with cognitive behavioral therapy for insomnia (CBT-I) reduces p16INK4a gene expression in peripheral blood: secondary outcome analysis from a randomized clinical trial

Late life insomnia may increase risk for accelerated biological aging. Intervening to treat insomnia may provide protection from biological aging by reducing the prevalence of senescent cells in the immune system, as indicated by gene expression of a marker of cellular senescence, p16(INK4a). In the present study, we determine whether treatment of insomnia in older adults with cognitive behavioral therapy for insomnia (CBT-I) would reduce p16(INK4a) gene expression in peripheral blood mononuclear cells (PBMC), compared to a sleep education therapy (SET), an active comparator condition. Secondly, we investigate the relationship between sustained insomnia remission and reduced expression of p16(INK4a). Participants 60 + years old with insomnia were enrolled in a randomized controlled trial and assigned to CBT-I or SET. Analyses of 231 older adults (CBT-I = 119; SET = 112) examine baseline, post (2 months), and 24 months gene expression of p16(INK4a). Compared to baseline, expression of p16(INK4a) increased in the SET group over 24 months (P = 0.03), but showed no change in the CBT-I group. Those who received CBT-I and experienced sustained remission of insomnia had a significant decline in p16(INK4a) expression by 24 months compared to baseline (P = 0.02). Individuals not sustaining remission of insomnia exhibited overall increase expression of p16(INK4a) by 24 months (P = 0.03). In older adults with insomnia, p16(INK4a) increases over 24 months, while CBT-I treatment of insomnia mitigates the increase in p16(INK4a). Further, sustained remission of insomnia using CBT-I leads to a decrease in p16(INK4a). These results suggest that behavioral interventions that are effective at treating insomnia might reduce the population of senescent cells in circulating blood.