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Epigenetic Regulation01:37

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

A Mongelli1,2, S Panunzi3, M Nesta4

  • 1Laboratorio di Epigenetica, Istituti Clinici Scientifici (ICS) Maugeri IRCCS, 27100, Pavia, Italy.

Clinical Epigenetics
|March 29, 2023
PubMed
Summary
This summary is machine-generated.

This study developed new epigenetic clocks for blood and heart, revealing similarities between chronological and biological age. The cardiac clock effectively differentiated between aortic valvular replacement and coronary artery bypass graft patients.

Keywords:
AgingCardiovascular diseaseDNA methylationDNAmAgeEpigenetic clockHeart biological agePyrosequencingRisk factors

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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.