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DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936

DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936
DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936
Background: The biological mechanisms underlying frailty in older people are poorly understood. There is some evidence to suggest that DNA methylation patterns may be altered in frail individuals.

Methods: Participants were 791 people aged 70 years from the Lothian Birth Cohort 1936. DNA methylation was measured in whole blood. Biological age was estimated using two measures of DNA methylation-based age acceleration - extrinsic and intrinsic epigenetic age acceleration. We carried out an epigenome-wide association study of physical frailty, as defined by the Fried phenotype. Multinomial logistic regression was used to calculate relative risk ratios for being physically frail or pre-frail according to epigenetic age acceleration.

Results: There was a single significant (P=1.16x10-7) association in the epigenome-wide association study comparing frail versus not frail. The same CpG was not significant when comparing pre-frail versus not frail. Greater extrinsic epigenetic age acceleration was associated with an increased risk of being physically frail, but not of being pre-frail. For a year increase in extrinsic epigenetic age acceleration, age- and sex-adjusted relative risk ratios (95% CI) for being physically frail or pre-frail were 1.06 (1.02, 1.10) and 1.02 (1.00, 1.04) respectively. After further adjustment for smoking and chronic disease, the association with physical frailty remained significant. Intrinsic epigenetic age acceleration was not associated with physical frailty status.

Conclusions: People who are biologically older, as indexed by greater extrinsic epigenetic age acceleration, are more likely to be physically frail. Future research will need to investigate whether epigenetic age acceleration plays a causal role in the onset of physical frailty.
1868-7075
Gale, Catharine
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Marioni, Riccardo E.
dd8c1d6f-c3ed-464a-8c41-50bc9b1a0aad
Harris, Sarah E.
925adc32-c478-44a2-84c0-1c7eefa8dfc8
Starr, John M.
92fc6cf8-b0f7-47dc-93d8-8fd246d40585
Deary, Ian J.
027158ae-fbfb-40ea-98b1-32d2690499ac
Gale, Catharine
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Marioni, Riccardo E.
dd8c1d6f-c3ed-464a-8c41-50bc9b1a0aad
Harris, Sarah E.
925adc32-c478-44a2-84c0-1c7eefa8dfc8
Starr, John M.
92fc6cf8-b0f7-47dc-93d8-8fd246d40585
Deary, Ian J.
027158ae-fbfb-40ea-98b1-32d2690499ac

Gale, Catharine, Marioni, Riccardo E., Harris, Sarah E., Starr, John M. and Deary, Ian J. (2018) DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936. Clinical Epigenetics. (doi:10.1186/s13148-018-0538-4).

Record type: Article

Abstract

Background: The biological mechanisms underlying frailty in older people are poorly understood. There is some evidence to suggest that DNA methylation patterns may be altered in frail individuals.

Methods: Participants were 791 people aged 70 years from the Lothian Birth Cohort 1936. DNA methylation was measured in whole blood. Biological age was estimated using two measures of DNA methylation-based age acceleration - extrinsic and intrinsic epigenetic age acceleration. We carried out an epigenome-wide association study of physical frailty, as defined by the Fried phenotype. Multinomial logistic regression was used to calculate relative risk ratios for being physically frail or pre-frail according to epigenetic age acceleration.

Results: There was a single significant (P=1.16x10-7) association in the epigenome-wide association study comparing frail versus not frail. The same CpG was not significant when comparing pre-frail versus not frail. Greater extrinsic epigenetic age acceleration was associated with an increased risk of being physically frail, but not of being pre-frail. For a year increase in extrinsic epigenetic age acceleration, age- and sex-adjusted relative risk ratios (95% CI) for being physically frail or pre-frail were 1.06 (1.02, 1.10) and 1.02 (1.00, 1.04) respectively. After further adjustment for smoking and chronic disease, the association with physical frailty remained significant. Intrinsic epigenetic age acceleration was not associated with physical frailty status.

Conclusions: People who are biologically older, as indexed by greater extrinsic epigenetic age acceleration, are more likely to be physically frail. Future research will need to investigate whether epigenetic age acceleration plays a causal role in the onset of physical frailty.

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Accepted/In Press date: 27 July 2018
e-pub ahead of print date: 3 August 2018

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Local EPrints ID: 422670
URI: https://eprints.soton.ac.uk/id/eprint/422670
ISSN: 1868-7075
PURE UUID: 7eecfc27-f2f8-4737-bc72-efe48d7a1f1b
ORCID for Catharine Gale: ORCID iD orcid.org/0000-0002-3361-8638

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Date deposited: 30 Jul 2018 16:30
Last modified: 10 Dec 2019 01:54

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Author: Catharine Gale ORCID iD
Author: Riccardo E. Marioni
Author: Sarah E. Harris
Author: John M. Starr
Author: Ian J. Deary

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