How Epigenetic Clocks Change with Age
Epigenetic clocks estimate biological age from DNA methylation marks. This page summarises research on how clock readings shift with age, and how interventions such as nicotinamide riboside and high-intensity interval tr
What epigenetic clocks measure
Epigenetic clocks are statistical models that estimate biological age from DNA methylation marks, most commonly at CpG sites in blood or saliva. The difference between estimated biological age and chronological age is termed epigenetic age acceleration (EAA); positive EAA indicates a biological age older than expected, negative EAA younger [2]. EAA has been associated with ageing-related functional decline and disease risk, and is used as an outcome in lifestyle and supplementation studies [1][2].
The work described here centres on DNA methylation-based ageing models and their response to interventions targeting mitochondrial and NAD+-dependent pathways [1].
Research Studies
Nicotinamide riboside and epigenetic age acceleration in human skeletal muscle
Nicotinamide riboside (NR) is a vitamin B3 precursor to NAD+. In a study assessing the impact of 5-month NR supplementation on epigenetic age acceleration in human skeletal muscle, seven epigenetic clocks were applied across three independent studies. NR supplementation was associated with a change in EAA in this tissue [1].
High-intensity interval training and epigenetic age acceleration in human skeletal muscle
The same investigation assessed 4–6 weeks of high-intensity interval training (HIIT) in human skeletal muscle. HIIT was proposed to ameliorate ageing-related mitochondrial decline, and its effects on epigenetic ageing were compared with those of NR [1].
Divergent effects of NR and HIIT on skeletal muscle epigenetic ageing
The study reported divergent effects of NR and HIIT on skeletal muscle epigenetic ageing, indicating that the two interventions did not shift epigenetic clock readings in the same direction or to the same degree in the tissue examined [1].
Seasonal variation and biological age in adults
A registered study aims to provide insights on how seasonal variations influence biological age and to enhance the design and analysis of long-term lifestyle interventions targeting biological clocks. Biological age clocks measured from blood or saliva are being used to assess the pace of ageing and to calculate age acceleration [2].
Genetic susceptibility to epigenetic age acceleration in Asian populations
A genome-wide association study of EAA using multiple epigenetic clocks was conducted in a Korean population to explore ethnic differences and individual variability in Asian populations [3].
Comparison of epigenetic clocks in ageing research
| Clock/model | Tissue | Outcome reported | Source |
|---|---|---|---|
| Seven epigenetic clocks | Human skeletal muscle | EAA after 5-month NR supplementation | [1] |
| Seven epigenetic clocks | Human skeletal muscle | EAA after 4–6 weeks HIIT | [1] |
| Multiple epigenetic clocks | Blood or saliva (adults) | Biological age and age acceleration | [2] |
| Multiple epigenetic clocks | Korean population | Genetic variants associated with EAA | [3] |
Age acceleration as an outcome measure
EAA is calculated as the difference between chronological and biological age, and is used to assess the pace of ageing in healthy individuals. Biological age clocks can be measured from samples such as blood or saliva [2].
Mitochondrial dysfunction and epigenetic alterations in ageing
Ageing is accompanied by a decline in physiological function and increased vulnerability to disease, with mitochondrial dysfunction and epigenetic alterations recognised as key hallmarks. NR and HIIT have both been proposed to ameliorate ageing-related mitochondrial decline, but their effects on skeletal muscle epigenetic ageing are not fully elucidated [1].
Study designs in epigenetic clock research
Three independent studies were used to assess the impact of NR supplementation and HIIT on EAA in human skeletal muscle [1]. A separate registered study is evaluating the effect of seasonality on biological age in adults [2]. A GWAS of EAA using multiple epigenetic clocks was conducted in a Korean population [3].
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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