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Related Concept Videos

Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

281
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
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Epigenetic Regulation01:37

Epigenetic Regulation

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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.
X-chromosome...
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Related Experiment Video

Updated: Aug 17, 2025

DNA Methylation: Bisulphite Modification and Analysis
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Published on: October 21, 2011

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DNA methylation GrimAge version 2.

Ake T Lu1,2, Alexandra M Binder3,4, Joshua Zhang1

  • 1Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

Aging
|December 14, 2022
PubMed
Summary
This summary is machine-generated.

GrimAge2, an improved epigenetic biomarker, enhances prediction of human mortality risk using DNA methylation. It shows stronger associations with age-related diseases and conditions like diabetes and cardiovascular disease.

Keywords:
DNA methylationepigenetic clockhealthspanmortality

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Area of Science:

  • Epigenetics
  • Biomarker Development
  • Gerontology

Background:

  • DNA methylation (DNAm) based biomarkers like GrimAge predict human mortality risk.
  • Previous versions require updates to improve accuracy and scope.

Purpose of the Study:

  • To introduce and evaluate GrimAge version 2 (GrimAge2), an enhanced DNAm biomarker for mortality risk.
  • To assess GrimAge2's performance against GrimAge and its association with various health outcomes.

Main Methods:

  • GrimAge2 was developed using DNAm estimators for high-sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C).
  • Evaluated in 13,399 blood samples across nine cohorts, adjusting for age and sex.
  • Assessed associations with mortality, coronary heart disease, lung function (FEV1), fatty liver disease, metabolic syndrome markers, type 2 diabetes, triglycerides, and visceral fat.

Main Results:

  • GrimAge2 significantly outperforms GrimAge in predicting mortality across diverse racial/ethnic groups (meta P=3.6x10-167).
  • Demonstrates strong associations with age-related conditions, including reduced lung function (FEV1 correlation=-0.31) and fatty liver disease.
  • DNAm logCRP correlates with morbidity, DNAm logA1C with type 2 diabetes, and DNAm PAI-1 with triglycerides and visceral fat.

Conclusions:

  • GrimAge version 2 is a superior epigenetic biomarker for predicting human mortality risk.
  • It shows broad applicability across different populations, sample types (blood and saliva), and age groups.
  • GrimAge2 and its component biomarkers offer valuable insights into morbidity and age-related disease risk.