What does the research say about PhenoAge?
PhenoAge is a biological age clock derived from clinical biomarkers. This page summarises the registered research on PhenoAge, including seasonal variation and intervention studies, and states where evidence is limited t
What is PhenoAge?
PhenoAge is a biological age clock, a composite score calculated from routine clinical biomarkers and chronological age, used to estimate the pace of ageing and to calculate age acceleration — the difference between chronological and biological age [1]. It is one of several biological age clocks that can be measured from samples such as blood or saliva [1]. The term 'PhenoAge' is used in the research literature to distinguish this clinical-biomarker-based clock from epigenetic clocks, which are derived from DNA methylation patterns [1][3].
The work on PhenoAge centres on the biology of ageing and the pathways that link metabolic and cellular function to age-related decline; the broader field of biological age clocks is concerned with identifying biomarkers that predict functional capability in healthy individuals [1].
Research Studies
PhenoAge and seasonal variation in adults
A registered clinical study is evaluating the effect of seasonality on biological age in adults [1]. The study aims to provide insights into how seasonal variations influence biological age and to enhance the design and analysis of long-term lifestyle interventions targeting biological clocks [1]. This research is ongoing; no results are available in the evidence reviewed here.
PhenoAge and calcium alpha-ketoglutarate in middle-aged and older adults
A randomised, double-blind, placebo-controlled clinical trial is evaluating the effects of calcium alpha-ketoglutarate (CaAKG) supplementation on biological ageing and age-related health indicators in middle-aged and older adults [2]. Alpha-ketoglutarate (AKG) is a key intermediate in the Krebs cycle and has been investigated for its potential role in modulating ageing-related metabolic and cellular pathways [2]. Because free AKG has poor oral bioavailability, the stabilised form CaAKG is used to enhance absorption and additionally provides calcium supplementation [2]. At the population level, there is currently a lack of systematic assessment studies on the effects of CaAKG [2]. This trial is ongoing; no results are available in the evidence reviewed here.
PhenoAge and genetic susceptibility in Asian populations
A genome-wide association study (GWAS) of epigenetic age acceleration (EAA) was conducted using multiple epigenetic clocks in a Korean population [3]. The study was designed to explore ethnic differences and individual variability in Asian populations [3]. This work concerns epigenetic clocks rather than PhenoAge specifically, but it contributes to the broader understanding of biological age clocks and their genetic underpinnings [3].
PhenoAge and epigenetic clocks: a comparison
PhenoAge and epigenetic clocks are both biological age clocks, but they are derived from different types of data. The table below summarises the distinction as described in the evidence reviewed here.
| Clock type | Data source | Example use in evidence |
|---|---|---|
| PhenoAge | Clinical biomarkers and chronological age [1] | Seasonality study in adults [1] |
| Epigenetic clocks | DNA methylation patterns [3] | GWAS of epigenetic age acceleration in a Korean population [3] |
PhenoAge and age acceleration
Age acceleration is the difference between chronological and biological age [1]. Biological age clocks, including PhenoAge, are emerging as valuable tools for assessing the pace of ageing and calculating age acceleration [1]. The evidence reviewed here does not specify particular mechanisms or tissues for PhenoAge beyond its derivation from clinical biomarkers.
PhenoAge and lifestyle interventions
The seasonality study aims to enhance the design and analysis of long-term lifestyle interventions targeting biological clocks [1]. This indicates that PhenoAge may be used as an outcome measure in intervention research, but the evidence reviewed here does not report results from such interventions.
PhenoAge and metabolic pathways
Alpha-ketoglutarate is a key intermediate in the Krebs cycle and has been investigated for its potential role in modulating ageing-related metabolic and cellular pathways [2]. The CaAKG trial uses biological ageing as an outcome, which may include clocks such as PhenoAge, but the evidence reviewed here does not specify which clocks are used [2].
PhenoAge in animal and in vitro research
The evidence reviewed here does not include animal-only or in vitro studies of PhenoAge. The studies identified are registered clinical trials and a human GWAS [1][2][3].
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Sources
- [1] Evaluation of the Effect of Seasonality on Biological Age in Adults (ClinicalTrials.gov)
- [2] Evaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging (ClinicalTrials.gov)
- [3] A genome-wide association study identifies Asian-specific genetic susceptibility for epigenetic age acceleration (Europe PMC)