Obesity accelerates epigenetic aging of human liver | Zendy

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

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Obesity accelerates epigenetic aging of human liver

Author(s) -

Steve Horvath,

Wiebke Erhart,

Mario Brosch,

Ole Ammerpohl,

Witigo von Schönfels,

M 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

Publication year - 2014

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.1412759111

Subject(s) - epigenetics , biological age , obesity , biomarker , biology , body mass index , human obesity , cellular aging , bioinformatics , medicine , oncology , endocrinology , genetics , evolutionary biology , gene , telomere

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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