Join us for an insightful presentation by Steve Horvath, PhD, Professor, Division of Geriatrics, David Geffen School of Medicine, UCLA.  Director, Aging Biology Research, Department of Medicine.

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Title:  "Epigenetic Clocks: Statistical Foundations, Emerging Computational Challenges, and What They Still Can't Tell Us"

Abstract:  DNA methylation clocks have become the most widely used molecular estimators of biological age, and they are increasingly deployed as surrogate endpoints in geroscience trials. In this talk I will lay out how epigenetic clocks are actually built (from penalized regression to deep learning on high-dimensional methylation data), the choice of training outcome (chronological age, phenotypic age, mortality risk, pace of aging), and the consequences those choices have for what a clock measures. I will then turn to the problems that remain open: technical noise and low reliability at the CpG level, confounding by cell-type composition, the fact that clocks are trained on cross-sectional data but interpreted longitudinally, and the persistent gap between predictive association and causal relevance. I will discuss recent work on causal versus non-causal CpGs, single-cell and cell-type-resolved clocks, and what would be required for an epigenetic age measure to serve as a credible surrogate endpoint. The talk is aimed at a bioinformatics and clinical data science audience. I will be explicit about where I think the methods are heading and where they currently fall short.

Biography:  Steve Horvath is Professor of Medicine in the Division of Geriatrics at the David Geffen School of Medicine, UCLA, and Director of Aging Biology Research in the Department of Medicine. Trained in mathematics and biostatistics, he works at the interface of computational biology and the biology of aging. He developed the epigenetic clock method for estimating biological age from DNA methylation data, and subsequent biomarkers including second generation clocks such as GrimAge, and the mammalian methylation clocks, which extend the approach across more than 300 species. He is a founder of the non-profit Epigenetic Clock Development Foundation, and was previously a Principal Investigator at Altos Labs.