Obesity accelerates epigenetic aging of human liver

Steve Horvath; Wiebke Erhart; Mario Brosch; Ole Ammerpohl; Witigo Von Schönfels; Markus Ahrens; Nils Heits; Jordana T. Bell; Pei Chien Tsai; Tim D. Spector; Panos Deloukas; Reiner Siebert; Bence Sipos; Thomas Becker; Christoph Röcken; Clemens Schafmayer; Jochen Hampe

doi:10.1073/pnas.1412759111

Obesity accelerates epigenetic aging of human liver

Steve Horvath^*, Wiebke Erhart, Mario Brosch, Ole Ammerpohl, Witigo Von Schönfels, Markus Ahrens, Nils Heits, Jordana T. Bell, Pei Chien Tsai, Tim D. Spector, Panos Deloukas, Reiner Siebert, Bence Sipos, Thomas Becker, Christoph Röcken, Clemens Schafmayer, Jochen Hampe

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

537 Scopus citations

Abstract

Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10^-4 in dataset 1 and r = 0.42, P = 1.2 × 10^-4 in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10^-9) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

Original language	English
Pages (from-to)	15538-15543
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	43
DOIs	https://doi.org/10.1073/pnas.1412759111
State	Published - 28 10 2014
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2014, National Academy of Sciences. All rights reserved.

Keywords

Aging
Biological age
DNA methylation
Epigenetics
Obesity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.1412759111

Cite this

Horvath, S., Erhart, W., Brosch, M., Ammerpohl, O., Von Schönfels, W., Ahrens, M., Heits, N., Bell, J. T., Tsai, P. C., Spector, T. D., Deloukas, P., Siebert, R., Sipos, B., Becker, T., Röcken, C., Schafmayer, C., & Hampe, J. (2014). Obesity accelerates epigenetic aging of human liver. Proceedings of the National Academy of Sciences of the United States of America, 111(43), 15538-15543. https://doi.org/10.1073/pnas.1412759111

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abstract = "Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an {"}epigenetic clock{"}) to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10-4 in dataset 1 and r = 0.42, P = 1.2 × 10-4 in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10-9) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.",

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Horvath, S, Erhart, W, Brosch, M, Ammerpohl, O, Von Schönfels, W, Ahrens, M, Heits, N, Bell, JT, Tsai, PC, Spector, TD, Deloukas, P, Siebert, R, Sipos, B, Becker, T, Röcken, C, Schafmayer, C & Hampe, J 2014, 'Obesity accelerates epigenetic aging of human liver', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 43, pp. 15538-15543. https://doi.org/10.1073/pnas.1412759111

TY - JOUR

T1 - Obesity accelerates epigenetic aging of human liver

AU - Horvath, Steve

AU - Erhart, Wiebke

AU - Brosch, Mario

AU - Ammerpohl, Ole

AU - Von Schönfels, Witigo

AU - Ahrens, Markus

AU - Heits, Nils

AU - Bell, Jordana T.

AU - Tsai, Pei Chien

AU - Spector, Tim D.

AU - Deloukas, Panos

AU - Siebert, Reiner

AU - Sipos, Bence

AU - Becker, Thomas

AU - Röcken, Christoph

AU - Schafmayer, Clemens

AU - Hampe, Jochen

PY - 2014/10/28

Y1 - 2014/10/28

N2 - Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10-4 in dataset 1 and r = 0.42, P = 1.2 × 10-4 in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10-9) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

AB - Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10-4 in dataset 1 and r = 0.42, P = 1.2 × 10-4 in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10-9) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

KW - Aging

KW - Biological age

KW - DNA methylation

KW - Epigenetics

KW - Obesity

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U2 - 10.1073/pnas.1412759111

DO - 10.1073/pnas.1412759111

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C2 - 25313081

AN - SCOPUS:84908441328

SN - 0027-8424

VL - 111

SP - 15538

EP - 15543

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 43

ER -

Obesity accelerates epigenetic aging of human liver

Abstract

Bibliographical note

Keywords

UN SDGs

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