Abstract MP17: Circulating Sirt1 And Endothelial Function Are Lower, But Are Not Improved By 8-weeks Of Exercise Training, In Young Adult Females With A History Of Adverse Childhood Experiences.
Authors: Nathaniel D Jenkins, Emily M Rogers, Nile F Banks, Christina M Sciarrillo, Sam Emerson, Ashlee Taylor, Kent Teague
Journal: Circulation (2021)

Introduction: Adverse Childhood Experiences (ACEs), in the forms of abuse, neglect, and violence, are associated with augmented blood pressures in young adulthood and CVD risk later in life. These effects are independent of negative health behaviors, suggesting that ACEs are biologically embedded. Sirtuin 1 (SIRT1) is a highly conserved nicotinamide-adenine dinucleotide-dependent deacetylase that plays an important role in the regulation of vascular function in aerobic organisms, while endothelial dysfunction is an antecedent of overt CVD. Hypotheses: We hypothesized that 1) circulating SIRT1 concentrations and endothelial function (EF) would be lower in young adult females with a history of ACEs when compared to age-matched controls with no history of ACEs, and 2) that 8-weeks of exercise training would improve circulating SIRT1 and EF in those with ACEs (ACE EXT ) compared to non-exercise controls with (ACE CON ) or without (NEG CON ) a history of ACEs. Methods: Forty-two young adult females (mean ± SE, age = 21 ± 0.4 y) were randomly assigned to either the ACE EXT (n = 14) or ACE CON group (n = 14) if their ACE score was ≥ 4, or assigned to the NEG CON group (n = 14) if their ACE score was 0. Prior to and after an 8-week intervention, serum was obtained from fasting venous blood draws for SIRT1 quantification via ELISA, and EF was assessed by quantifying flow-mediated dilation (FMD) using duplex ultrasound of the brachial artery. During the intervention, females in the ACE EXT group completed 2 sessions each of resistance and aerobic interval training every week, whereas the ACE CON and NEG CON groups maintained habitual activity levels. Effects of ACEs were examined by collapsing the ACE groups and comparing them to the NEG CON group with unpaired comparisons (ACE vs. NEG CON ), whereas the group*intervention interaction was assessed using a one-way ANOVA on the absolute change scores (ACE EXT vs. ACE CON vs. NEG CON ). Results: SIRT1 (649.6 ± 27.0 vs. 809.5 ± 51.0 pg/ml; t 38 = 3.05, p = 0.004) and EF were lower (6.0 ± 0.7 vs. 9.4 ± 0.9%; U = 77.5, p = 0.002) in the females exposed to ACEs compared to the controls. Further, EF was moderately related ( rho = 0.58, p &lt; 0.001) to SIRT1 concentrations at baseline across the sample. However, 8-weeks of exercise training resulted in no significant improvements in either circulating SIRT1 ( p = 0.94) or FMD ( p = 0.16). Conclusions: This is the first study, to our knowledge, to examine the influence of ACEs on SIRT1 levels and endothelial function. Our data provide initial evidence that young adult females with a history of ACEs exhibit decreased vascular function early in adulthood, which may help explain the increased risk of CVD associated with ACEs. Importantly, our data also suggest that SIRT1 may be an important link between ACEs and vascular dysfunction. However, the 8-week exercise intervention was not effective for improving either outcome in those with a history of ACEs in this study.