What does the research say about epigenetic clocks?
Epigenetic clocks are DNA methylation-based estimators of biological age. Research has examined their response to interventions such as nicotinamide riboside and HIIT, and their genetic and seasonal determinants.
What are epigenetic clocks?
Epigenetic clocks are statistical models that estimate biological age from DNA methylation patterns. They are also referred to as biological age clocks or DNA methylation age estimators. These clocks are not physical instruments but algorithms that combine methylation levels at specific CpG sites to produce an age estimate. The difference between estimated biological age and chronological age is termed epigenetic age acceleration (EAA). EAA can be measured in accessible tissues such as blood or saliva, and it is used in research to assess the pace of aging [2].
The work on epigenetic clocks centres on DNA methylation, a covalent modification of cytosine residues in CpG dinucleotides, and the enzymatic machinery that writes, reads, and erases these marks, including DNA methyltransferases and ten-eleven translocation (TET) enzymes.
Research Studies
Nicotinamide riboside and epigenetic age acceleration in human skeletal muscle
Nicotinamide riboside (NR), a vitamin B3 precursor to NAD+, has been investigated for its effects on aging-related mitochondrial decline. In a study assessing the impact of 5-month NR supplementation on epigenetic age acceleration in human skeletal muscle, NR was associated with changes in EAA as measured by seven epigenetic clocks across three independent studies [1]. The direction and magnitude of these associations varied among the clocks, and the study design does not establish causality.
High-intensity interval training and epigenetic age acceleration in human skeletal muscle
The same research programme evaluated 4–6 weeks of high-intensity interval training (HIIT) for its effects on skeletal muscle epigenetic aging. HIIT was proposed to ameliorate aging-related mitochondrial decline, but its effects on epigenetic age acceleration were not fully elucidated. The study reported divergent effects of NR and HIIT on EAA, indicating that the two interventions do not act identically on epigenetic clocks in this tissue [1].
Comparison of nicotinamide riboside and HIIT effects on epigenetic clocks
The table below summarises the intervention parameters and the epigenetic clock outcomes reported in the human skeletal muscle study [1].
| Intervention | Duration | Tissue | Epigenetic clocks used | Reported effect on EAA |
|---|---|---|---|---|
| Nicotinamide riboside (NR) | 5 months | Human skeletal muscle | Seven clocks | Associated with changes in EAA |
| High-intensity interval training (HIIT) | 4–6 weeks | Human skeletal muscle | Seven clocks | Divergent effects compared with NR |
Seasonality and biological age in adults
A clinical study is examining how seasonal variations influence biological age, with the aim of improving the design and analysis of long-term lifestyle interventions targeting biological clocks. 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.
Genetic susceptibility to epigenetic age acceleration in Asian populations
Genome-wide association studies (GWASs) have been performed on multiple epigenetic clocks to understand the genetic underpinnings of EAA. To explore ethnic differences and individual variability, a GWAS of EAA using multiple epigenetic clocks was conducted in a Korean population [3]. This work identified Asian-specific genetic susceptibility loci for epigenetic age acceleration, highlighting that genetic determinants of EAA can differ by ancestry.
Epigenetic clocks as biomarkers in aging research
Biological age clocks are emerging as tools for assessing the pace of aging and calculating age acceleration. They can be measured from blood or saliva, making them accessible for longitudinal studies. Their utility in predicting functional capability in healthy individuals is an active area of investigation [2].
Mitochondrial dysfunction and epigenetic alterations as hallmarks of aging
Aging is accompanied by a decline in physiological function and increased vulnerability to disease. Mitochondrial dysfunction and epigenetic alterations are recognised as key hallmarks of this process. Interventions such as NR and HIIT have been proposed to target aging-related mitochondrial decline, but their effects on epigenetic aging are not fully elucidated [1].
Methodological considerations in epigenetic clock research
Studies of epigenetic clocks employ multiple algorithms, and results can vary depending on the clock used. In the human skeletal muscle study, seven epigenetic clocks were applied, and the effects of NR and HIIT were assessed across three independent studies [1]. The choice of clock, tissue, and intervention duration can influence the observed EAA. Standardisation and replication across populations remain important challenges [3].
If you are reading this for personal health reasons
The materials and interventions discussed here are for laboratory research only. We do not provide dosing or medical guidance. Anyone considering a compound or intervention for themselves should speak to a licensed clinician.
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