To quantify how cumulative childhood adversity accelerates biological aging—and to test whether psychosocial resilience factors and trauma-informed therapy can slow or reverse that acceleration—using a multi-clock epigenetic approach in children, adolescents, and young adults.
Specific Aims
Aim
Question
Read-outs
1. Baseline association
Does a higher Adverse Childhood Experiences (ACE) score predict faster epigenetic aging at study entry?
Does participation in evidence-based, trauma-focused therapy reduce the annual rate of clock advancement over 24 months?
Δ clock / year (months) between baseline and M24.
Primary Hypotheses
H1 (Age-acceleration): Participants with high cumulative ACE scores (≥ 4) will exhibit ≥ 1.5 years of epigenetic age acceleration relative to chronological age, averaged across clocks, compared with low-ACE controls (≤ 1).
H2 (Therapy effect): Among high-ACE participants, those who complete ≥ 12 sessions of trauma-informed CBT will show a ≥ 25 % reduction in annual epigenetic-clock progression (Δ clock/yr) versus wait-list peers over 24 months.
Secondary / Mechanistic Hypotheses
Code
Testable prediction
Statistical model
H2a (Buffering)
Better sleep efficiency (top tertile of actigraphy) will attenuate the ACE → age-acceleration slope by ≥ 40 %.
ACE × Sleep interaction term in LMM.
H2b (Inflammatory amplification)
Elevated baseline CRP (> 3 mg/L) will strengthen the ACE → acceleration association by ≥ 0.3 SD.
ACE × CRP interaction.
H3 (Clock concordance)
DunedinPACE will be more sensitive to therapy-induced change than GrimAge (paired Δ differences > 0.3 years, p < 0.05).
Repeated-measures ANOVA.
Null hypotheses (for protocol clarity)
H0-1: No difference in baseline epigenetic age acceleration between high- and low-ACE groups.
H0-2: Trauma-informed therapy does not change the annual rate of epigenetic aging compared with wait-list controls.
Use
Grant applications: Paste the Objective paragraph at the top of the Specific Aims page; list Aims and hypotheses beneath.
IRB protocol: Insert the Objective under “1.0 Study Purpose” and the hypotheses under “2.0 Study Endpoints.”
ClinicalTrials.gov: A 25-word public title could read: “RESET Study: Childhood adversity, epigenetic aging, and resilience-based therapy in youth and young adults.”
