Journal September 26, 2026 4 min read

How does GrimAge work?

GrimAge is a second-generation epigenetic clock that incorporates plasma protein surrogates and smoking history to estimate mortality risk. This article explains its construction, the DNA methylation sites it uses, and t

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What is GrimAge?

GrimAge is a DNA methylation-based epigenetic clock designed to estimate biological age and predict mortality risk. Unlike first-generation clocks such as Horvath and Hannum, which were trained solely on chronological age, GrimAge was trained on time-to-death and composite clinical outcomes. It is formally known as the GrimAge epigenetic clock, and its output is often expressed as GrimAge acceleration (GrimAgeAccel), the residual from regressing GrimAge on chronological age. The clock uses DNA methylation data, typically from blood or saliva, and is calculated from a set of CpG sites. The exact number of CpGs and their identities are defined in the original publication; the evidence block does not provide these identifiers.

GrimAge is not a single biomarker but a composite of DNA methylation surrogates for plasma proteins and smoking pack-years. The pathway or receptor family most central to its mechanism is the DNA methylation machinery that regulates gene expression, though the clock itself is a statistical predictor rather than a direct measure of a specific biological pathway.

Research Studies

GrimAge and epigenetic age acceleration in Asian populations

A genome-wide association study (GWAS) of epigenetic age acceleration (EAA) was conducted in a Korean population using multiple epigenetic clocks, including GrimAge. The study aimed to explore ethnic differences and individual variability in EAA. The findings identified Asian-specific genetic susceptibility loci for EAA, suggesting that genetic determinants of epigenetic aging may differ across populations [3]. This work is REFERENCE ONLY and supports the broader context of GrimAge as a measurable trait with genetic underpinnings.

GrimAge and seasonal variation in biological age

A clinical study is evaluating the effect of seasonality on biological age in adults. The research aims to provide insights on how seasonal variations influence biological age and enhance the design and analysis of long-term lifestyle interventions targeting biological clocks. Biological age clocks, including GrimAge, can be measured from samples like blood or saliva and are emerging as valuable tools for assessing the pace of aging and calculating age acceleration—the difference between chronological and biological age [1]. This study is ongoing and has not yet reported results.

GrimAge and autologous bone marrow procedures in Parkinson's disease

A pilot study evaluated the safety, tolerability, and exploratory epigenetic outcomes of a single same-day autologous bone marrow procedure in adults with Parkinson's disease (PD) or Parkinson-plus syndromes (PPS). Ten participants underwent bone marrow aspiration, with unprocessed aspirate administered intravenously and a concentrate administered intranasally. The study included exploratory epigenetic outcomes, which may involve GrimAge or other epigenetic clocks, but the evidence block does not specify which clocks were used or report any results [2]. This study is ongoing or completed, but no epigenetic findings are available in the provided evidence.

GrimAge and mortality prediction

The evidence block does not contain studies directly reporting GrimAge's mortality prediction performance. The original GrimAge publication is not included in the evidence block, so no specific effect sizes or hazard ratios can be cited here.

GrimAge and lifestyle interventions

The evidence block does not contain studies of lifestyle interventions specifically targeting GrimAge. The seasonality study [1] mentions lifestyle interventions targeting biological clocks, but no results are reported.

GrimAge and comparison with other epigenetic clocks

The evidence block does not provide comparative data between GrimAge and other clocks. The GWAS study [3] used multiple epigenetic clocks, but the results are not detailed in the evidence block.

GrimAge and tissue specificity

The evidence block does not contain studies on tissue specificity of GrimAge. The seasonality study [1] notes that biological age clocks can be measured from blood or saliva, but no specific findings for GrimAge are provided.

GrimAge and clinical outcomes

The evidence block does not contain studies linking GrimAge to specific clinical outcomes other than the general mention of mortality risk in the context of epigenetic clocks [1]. No specific disease outcomes are reported.

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