Distinguishable DNA methylation defines a cardiac-specific epigenetic clock

Area of Science:

• Epigenetics
• Cardiovascular Science
• Aging Research

Background:

• Investigates epigenetic differences in the heart following cardiac surgery (aortic valvular replacement - AVR, coronary artery bypass graft - CABG).
• Aims to establish an algorithm to assess how pathophysiological conditions influence biological cardiac age.

Purpose of the Study:

• To develop and validate novel blood- and cardiac-specific epigenetic clocks.
• To evaluate the relationship between chronological age, biological age, and cardiovascular health.
• To identify epigenetic markers distinguishing patient subgroups undergoing different cardiac procedures.

Main Methods:

• Collected blood and cardiac auricle samples from 94 AVR and 289 CABG patients.
• Selected 31 CpGs from six age-related genes to construct tissue-tailored clocks.
• Validated clocks using neural network analysis and elastic regression; measured telomere length (TL) via qPCR.

Main Results:

• Demonstrated similarity between chronological and biological age in blood and heart; heart TL was significantly higher than blood TL.
• The cardiac clock effectively discriminated between AVR and CABG patients.
• Cardiac clock sensitivity to cardiovascular risk factors (obesity, smoking) and identification of AVR subgroup with accelerated bioage linked to altered ventricular parameters.

Conclusions:

• Successfully applied a method to evaluate cardiac biological age using epigenetic features.
• Revealed distinct epigenetic profiles separating subgroups of AVR and CABG patients.
• The developed cardiac-specific clock holds potential for personalized risk assessment in cardiovascular surgery patients.