Epigenetic age acceleration is not associated with age-related macular degeneration
Epigenetic age acceleration is not associated with age-related macular degeneration
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.
Age-related macular degeneration, Ageing, DNA methylation, Epigenetic clock, Retinal pigment epithelium, Whole blood
Saptarshi, Neil
81c3f072-b9e2-4dd6-a671-69601ac6a37a
Green, Daniel
e2e7c936-2a7b-478d-89f7-fbc1c1f99b1c
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Paraoan, Luminita
252bc6c9-e9b1-4bbb-a2d3-d7fb91826b0e
Porter, Louise F.
d2e1c03d-bd5d-46cf-a96c-e25a47f2c69a
15 December 2021
Saptarshi, Neil
81c3f072-b9e2-4dd6-a671-69601ac6a37a
Green, Daniel
e2e7c936-2a7b-478d-89f7-fbc1c1f99b1c
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Paraoan, Luminita
252bc6c9-e9b1-4bbb-a2d3-d7fb91826b0e
Porter, Louise F.
d2e1c03d-bd5d-46cf-a96c-e25a47f2c69a
Saptarshi, Neil, Green, Daniel, Cree, Angela, Lotery, Andrew, Paraoan, Luminita and Porter, Louise F.
(2021)
Epigenetic age acceleration is not associated with age-related macular degeneration.
International Journal of Molecular Sciences, 22 (24), [13457].
(doi:10.3390/ijms222413457).
Abstract
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.
Text
ijms-22-13457
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Accepted/In Press date: 2 December 2021
Published date: 15 December 2021
Additional Information:
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.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
Keywords:
Age-related macular degeneration, Ageing, DNA methylation, Epigenetic clock, Retinal pigment epithelium, Whole blood
Identifiers
Local EPrints ID: 454784
URI: http://eprints.soton.ac.uk/id/eprint/454784
ISSN: 1661-6596
PURE UUID: 12567a63-9de2-43bb-b967-06fa61d7a08e
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Date deposited: 23 Feb 2022 17:37
Last modified: 18 Mar 2024 03:02
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Author:
Neil Saptarshi
Author:
Daniel Green
Author:
Luminita Paraoan
Author:
Louise F. Porter
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