Team AgingPrint

AgingPrint is a perturbation-informed immune aging clock that decomposes CD4+ T cell aging into three independent biological programs: pro-aging transcription, anti-aging transcription, and naive T cell composition. AgingPrint weights were derived from 305 genes associated with aging in two independent cohorts then weighted by causal evidence from genome-wide perturbation data. Existing clocks optimize weights to predict chronological age, then call the residual biological aging. AgingPrint inverts this –– the gap from chronological age is the finding, not the error. Applied to 91 unseen donors, AgingPrint retains 98% of its performance. In healthy donors, biological immune age is normally distributed with a standard deviation of nearly 10 years meaning only 20% of “healthy” donors fall within two years of their chronological age. This variation appears to be genuine biology, not measurement error. Applied to disease, the three-component attribution reveals mechanistic distinctions invisible to single-score clocks: lupus accelerates all three aging programs, tracking from managed disease to flare-ups. Severe COVID suppresses pro-aging transcription while depleting naive T cells. Alzheimer's shows almost no peripheral CD4+ T cell aging signal. This framework extends to any immune cell type with matched CRISPRi screening data, enabling multi-cell-type biological aging assessment from a standard blood draw.