Levine · Aging 2018 · observational biomarker development and validation study · n=?

An epigenetic biomarker of aging for lifespan and healthspan.

Cited 3747 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized observational biomarker development and cohort validation study

PubMed 29676998 · doi:10.18632/aging.101414 · record verified 2026-08-29

What was done

Authors developed a second-generation epigenetic aging biomarker, termed DNAm PhenoAge, using a two-step process incorporating composite clinical measures of phenotypic age reflecting lifespan and healthspan. The biomarker was developed using whole blood data and assessed across diverse tissues, cell types, and aging-related clinical outcomes, accompanied by transcriptional pathway analysis in sorted cells.

What was found

The abstract reports no numerical values, correlation coefficients, or hazard ratios. Qualitatively, DNAm PhenoAge was reported to outperform previous chronological age-trained measures in predicting all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. Epigenetic age acceleration was associated with increased activation of pro-inflammatory and interferon pathways, alongside decreased activation of transcriptional and translational machinery, DNA damage response, and mitochondrial signatures.

Why it matters

This work shifted epigenetic clock development toward multi-system phenotypic and functional outcomes, creating a tool to quantify biological aging and morbidity risk.

Limits

The abstract reports no sample sizes, demographic characteristics, or quantitative effect estimates. As an observational biomarker study, these associations do not demonstrate that the identified DNA methylation patterns causally drive phenotypic aging.

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