TY - JOUR
T1 - Epigenetic Age Acceleration Is Not Associated with Age-Related Macular Degeneration
AU - Saptarshi, Neil
AU - Green, Daniel
AU - Cree, Angela
AU - Lotery, Andrew
AU - Paraoan, Luminita
AU - Porter, Louise F
N1 - Funding Information:
Funding: L.F.P. is MCU-PH funded by the French Ministry of Health at the University of Strasbourg, France; previously an NIHR Clinical Lecturer at the University of Liverpool. This project was funded by Academy of Medical Sciences Starter Grant for Clinical Lecturers awarded to L.F.P. N.S. is supported by a National Eye Research Centre PhD Studentship. D.G. is funded by the MRC Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (MR/R502182/1). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The funders had no role in the design, data collection, analysis, or conclusions drawn from this study. AJL is an emeritus NIHR Senior Investigator and the Southampton AMD cohort was funded by Macula Vision Research Foundation, Macular Disease Society, British Council Prevention Blindness, T.F.C. Frost Charitable Trust, The Wellcome Trust, Brian Mercer Charitable Trust, De Laszlo Foundation and the Gift of Sight Appeal.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - DNA methylation age (DNAm age) estimation is a powerful biomarker of human ageing. To date, epigenetic clocks have not been evaluated in age-related macular degeneration (AMD). Here, we perform genome-wide DNA methylation analyses in blood of AMD patients with a documented smoking history (14 AMD, 16 Normal), identifying loci of differential methylation (DML) with a relaxed p-value criterion (p ≤ 10
−4 ). We conduct DNAm age analyses using the Horvath-multi tissue, Hannum and Skin & Blood epigenetic clocks in both blood and retinal pigment epithelium (RPE). We perform Ingenuity Pathway Analysis Causal Network Analysis (IPA CNA) on the topmost significantly differentially methylated CpG probes in blood and RPE. Results show poor performance of epigenetic clocks in RPE. Epigenetic age acceleration (EAA) was not observed in AMD. However, we observe positive EAA in blood of smokers, and in smokers with AMD. DML analysis revealed hypomethylation at cg04953735 within RPTOR (p = 6.51 × 10
−5; ∆β = −11.95%). IPA CNA in the RPE also identified RPTOR as the putative master regulator, predicted to be inhibited in AMD. In conclusion, this is the first study evaluating an association of epigenetic ageing in AMD. We posit a role for RPTOR as a common master regulator of methylation changes in the RPE in AMD.
AB - DNA methylation age (DNAm age) estimation is a powerful biomarker of human ageing. To date, epigenetic clocks have not been evaluated in age-related macular degeneration (AMD). Here, we perform genome-wide DNA methylation analyses in blood of AMD patients with a documented smoking history (14 AMD, 16 Normal), identifying loci of differential methylation (DML) with a relaxed p-value criterion (p ≤ 10
−4 ). We conduct DNAm age analyses using the Horvath-multi tissue, Hannum and Skin & Blood epigenetic clocks in both blood and retinal pigment epithelium (RPE). We perform Ingenuity Pathway Analysis Causal Network Analysis (IPA CNA) on the topmost significantly differentially methylated CpG probes in blood and RPE. Results show poor performance of epigenetic clocks in RPE. Epigenetic age acceleration (EAA) was not observed in AMD. However, we observe positive EAA in blood of smokers, and in smokers with AMD. DML analysis revealed hypomethylation at cg04953735 within RPTOR (p = 6.51 × 10
−5; ∆β = −11.95%). IPA CNA in the RPE also identified RPTOR as the putative master regulator, predicted to be inhibited in AMD. In conclusion, this is the first study evaluating an association of epigenetic ageing in AMD. We posit a role for RPTOR as a common master regulator of methylation changes in the RPE in AMD.
KW - Age-related macular degeneration
KW - Ageing
KW - DNA methylation
KW - Epigenetic clock
KW - Retinal pigment epithelium
KW - Whole blood
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U2 - 10.3390/ijms222413457
DO - 10.3390/ijms222413457
M3 - Article (journal)
C2 - 34948253
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 24
M1 - 13457
ER -