ABSTRACT: Importance:Telomere length is associated with the development of age-related diseases and structural differences in multiple brain regions. It remains unclear, however, whether change in telomere length is linked to brain structure change, and to what extent telomere length can be influenced through mental training. Objectives:To assess the dynamic associations between leukocyte telomere length (LTL) and cortical thickness (CT), and to determine whether LTL is affected by a longitudinal contemplative mental training intervention. Design, Setting, and Participants:An open-label efficacy trial of three 3-month mental training modules with healthy, meditation-naive adults was conducted. Data on LTL and CT were collected 4 times over 9 months between April 22, 2013, and March 31, 2015, as part of the ReSource Project. Data analysis was performed between September 23, 2016, and June 21, 2019. Of 1582 eligible individuals, 943 declined to participate; 362 were randomly selected for participation and assigned to training or retest control cohorts, with demographic characteristics matched. The retest control cohorts underwent all testing but no training. Intention-to-treat analysis was performed. Interventions:Training cohort participants completed 3 modules cultivating interoception and attention (Presence), compassion (Affect), or perspective taking (Perspective). Main Outcomes and Measures:Change in LTL and CT. Results:Of the 362 individuals randomized, 30 participants dropped out before study initiation (initial sample, 332). Data were available for analysis of the training intervention in 298 participants (n?=?222 training; n?=?76 retest control) (175 women [58.7%]; mean [SD] age, 40.5 [9.3] years). The training modules had no effect on LTL. In 699 observations from all 298 participants, mean estimated changes in the relative ratios of telomere repeat copy number to single-copy gene (T/S) were for no training, 0.004 (95% CI, -0.010 to 0.018); Presence, -0.007 (95% CI, -0.025 to 0.011); Affect, -0.005 (95% CI, -0.019 to 0.010); and Perspective, -0.001 (95% CI, -0.017 to 0.016). Cortical thickness change data were analyzed in 167 observations from 67 retest control participants (37 women [55.2%], mean [SD] age, 39.6 [9.0] years). In this retest control cohort subsample, naturally occurring LTL change was related to CT change in the left precuneus extending to the posterior cingulate cortex (mean t161?=?3.22; P?
