Objective: In the current study, we aim to evaluate whether Rapid-eye-movement sleep behavior disorder (RBD) age-at-onset and age-at-phenoconversion are associated with DNA methylation-age acceleration (DNAm-AA).
Background: RBD is the strongest prodromal marker for α‐synucleinopathies, including Parkinson’s disease and Lewy Body Dementia, for which aging is the strongest risk factor. The Horvath DNAm-age is an epigenetic clock that could reflect biological aging. Recently, age-at-onset of Parkinson’s disease was associated with DNAm-AA, which is the deviation of DNAm-age from chronological age.
Method: We analyzed blood DNA samples from 162 patients with idiopathic RBD diagnosed by polysomnography, including 45 patients with a longitudinal assessment (two time-points 2-10 years apart) and 53 patients who phenoconverted to either Parkinson’s disease or Lewy Body Dementia. Using the Infinium MethylationEPIC array (Illumina), we obtained DNAm data of 334 age-related CpG-sites constituting the Horvath DNAm-age adjusted for blood cell counts based on the advanced analysis mode of the DNAm-age calculator (https://dnamage.genetics.ucla.edu/). We applied multivariate linear regression to estimate the association between DNAm-AA and either RBD age-at-onset or age-at-phenoconversion. The analyses were adjusted for sex and interval (the difference between age at sample collection and RBD onset).
Results: We found an association of DNAm-AA with RBD age-at-onset at baseline (N=162; B=-0.68; SE=0.12; P=2.59e-08) and at follow-up in the longitudinal group (N=45; B=-1.07; SE=0.21; P=9.73e-06). We also observed that RBD patients with faster aging (DNAm-AA >3) had 4.6 years earlier age-at-onset than patients with slow/normal aging (DNAm-AA <3; 55.15±11.05 vs 59.71±10.06). Similarly, phenoconverters (N=53) showed an association between DNAm-AA and age-at-phenoconversion (B=-0.85; SE=0.21; P=1.26e-04). Patients with faster aging had earlier age-at-phenoconversion than patients with slow/normal aging (69.89±7.72 vs 75.06±7.96).
Conclusion: We demonstrated that epigenetic clock acceleration is associated with an earlier age-at-onset and age-at-phenoconversion in the RBD cohort. This is consistent with results previously reported for neurodegenerative diseases (i.e., Parkinson’s disease, Amyotrophic Lateral Sclerosis).
To cite this abstract in AMA style:
K. Senkevich, A. Pelletier, C. Sato, A. Keil, Z. Gan-Or, A. Lang, R. Postuma, E. Rogaeva. Epigenetic clock acceleration is linked to earlier onset and phenoconvertion of Rapid-eye-movement sleep behavior disorder [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/epigenetic-clock-acceleration-is-linked-to-earlier-onset-and-phenoconvertion-of-rapid-eye-movement-sleep-behavior-disorder/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/epigenetic-clock-acceleration-is-linked-to-earlier-onset-and-phenoconvertion-of-rapid-eye-movement-sleep-behavior-disorder/