On the Quantification of Aging

Abstract

This dissertation explores the complex biological process of aging through multiple methodological lenses, from molecular mechanisms to population-level analyses. As global demographics shift toward an increasingly older population, understanding aging mechanisms and developing interventions to extend healthy lifespan have become critical scientific priorities. Despite chronological age being the strongest risk factor for many diseases, individuals age at different rates, suggesting that chronological age alone is an insufficient measure of biological aging. This research addresses key challenges in aging research through a multifaceted approach combining traditional genetic and epidemiological analyses with advanced computational methods. The dissertation investigates causal relationships between aging and disease, develops causality-enriched epigenetic clocks, examines the role of germline mutations in exceptional longevity, constructs high-dimensional representations of aging, develops foundation models for analyzing complex aging-related data, establishes standardized frameworks for biomarker evaluation, and creates a unified theoretical definition of biological age. By pursuing these objectives, this work aims to contribute significantly to our understanding of the aging process and provide tools and frameworks that can accelerate research in this field.