2. Aging Clocks Measure Projections of Biological Age Onto Specific Data Layers

Currently existing aging clocks aim to measure biological age (as latent state of the deleteriome) using high-dimensional data (various omics, imaging, wearables, etc.) that correlates with time, phenotypes, and/or disease or mortality risk (11, 62, 63). In this framework, clock predictions are best viewed as readouts of aging projected onto the particular layer being measured. An epigenetic clock, for example, captures aspects of epigenetic state; a plasma proteomic clock captures circulating consequences of tissue aging; a transcriptomic clock captures gene-regulatory remodeling. No single clock represents true biological age, because biological age is not a single scalar property of the organism; it is a projection of a multidimensional state onto what a particular assay can see and what a model was trained to predict. Different clocks sample different layers (e.g., methylation vs transcripts vs proteins vs metabolites), tissues (e.g., blood, organ-specific), and processes (e.g., cell-state composition shifts, regulatory remodeling, inflammatory tone, damage responses). Multimodal clocks may be closer to ground truth and can outperform single-modality clocks in approximating biological age.