What markers track epigenetic clocks?
Epigenetic clocks estimate biological age from DNA methylation marks. This page outlines the markers and clocks used in research, including findings from human skeletal muscle and population studies.
Epigenetic clocks are composite biomarkers that estimate biological age from DNA methylation (DNAm) at specific CpG sites. The formal name for the underlying process is epigenetic age acceleration (EAA), defined as the difference between chronological age and epigenetic age estimated by a clock. EAA is typically calculated using algorithms such as Horvath, Hannum, PhenoAge, GrimAge, and others; the evidence block does not provide sequence, formula, or molecular weight for these clocks. The work centres on DNA methylation marks, particularly 5-methylcytosine at CpG dinucleotides, which are read by methyl-CpG-binding domain (MBD) proteins and ten-eleven translocation (TET) enzymes that mediate demethylation.
In research settings, epigenetic clocks are measured from DNA extracted from blood, saliva, or skeletal muscle. The markers that track these clocks are the methylation levels at clock-specific CpG sites, often aggregated into a single score. The following sections summarise studies that have examined how interventions or population factors relate to these markers.
Research Studies
Nicotinamide riboside and epigenetic aging in human skeletal muscle
Nicotinamide riboside (NR), a vitamin B3 precursor to NAD+, was tested for its effects on epigenetic age acceleration in human skeletal muscle. In a study assessing 5-month NR supplementation and 4–6 weeks of high-intensity interval training (HIIT) across three independent studies, NR supplementation was associated with changes in EAA as measured by seven epigenetic clocks [1]. The study reported divergent effects of NR and HIIT on skeletal muscle epigenetic aging, though the evidence block does not specify the direction or magnitude of these associations [1].
High-intensity interval training and epigenetic aging in human skeletal muscle
The same study evaluated HIIT and found that it also influenced epigenetic age acceleration in skeletal muscle, but the effects differed from those of NR [1]. The evidence block does not provide details on which clocks showed significant changes or the effect sizes. The study highlights that both interventions may modulate epigenetic aging, but their impacts are not uniform across clocks [1].
Seasonality and biological age in adults
A clinical trial is investigating how seasonal variations influence biological age, with the aim of enhancing the design and analysis of long-term lifestyle interventions targeting biological clocks [2]. The study measures biological age from samples such as blood or saliva and calculates age acceleration as the difference between chronological and biological age [2]. This research is ongoing and has not yet reported results in the evidence block.
Genetic susceptibility to epigenetic age acceleration in Asian populations
A genome-wide association study (GWAS) of epigenetic age acceleration using multiple epigenetic clocks was conducted in a Korean population to explore ethnic differences and individual variability [3]. The study identified Asian-specific genetic susceptibility loci for EAA, though the specific genes or variants are not detailed in the evidence block [3]. This finding suggests that genetic factors may influence epigenetic clock markers in a population-specific manner.
Comparison of epigenetic clocks in skeletal muscle
The study on NR and HIIT utilised seven epigenetic clocks to assess EAA in human skeletal muscle [1]. The table below summarises the clocks mentioned in the evidence block, though specific clock names are not provided.
| Clock | Number of clocks | Tissue | Study |
|---|---|---|---|
| Epigenetic clocks (unspecified) | 7 | Skeletal muscle | [1] |
| Epigenetic clocks (multiple) | Not specified | Blood or saliva | [2] |
| Epigenetic clocks (multiple) | Not specified | Not specified | [3] |
Markers of epigenetic aging: DNA methylation sites
The primary markers tracked by epigenetic clocks are DNA methylation levels at specific CpG sites. These sites are distributed across the genome and are often located in or near genes involved in aging-related pathways. The evidence block does not list specific CpG sites or genes, but the clocks aggregate methylation data to produce an estimate of biological age [1][2][3].
Epigenetic age acceleration as a marker
Epigenetic age acceleration (EAA) is a derived marker that represents the difference between epigenetic age and chronological age. Positive EAA indicates that biological age is greater than chronological age, while negative EAA indicates the opposite. EAA is used as an outcome in intervention studies and population research [1][2][3].
Population-specific genetic markers for EAA
The GWAS in a Korean population identified genetic variants associated with EAA, suggesting that genetic background may affect the markers that track epigenetic clocks [3]. This is a reference-only finding and does not constitute a section on its own; it supports the notion that epigenetic aging is influenced by both environmental and genetic factors.
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Sources
- [1] The Divergent Effects of Nicotinamide Riboside and High-Intensity Exercise Training on Skeletal Muscle Epigenetic Aging
- [2] Evaluation of the Effect of Seasonality on Biological Age in Adults
- [3] A genome-wide association study identifies Asian-specific genetic susceptibility for epigenetic age acceleration