The Principal Component Life Trajectory (PCLT): Mapping Sex-Specific Physiological Change Across the Human Lifespan

Age- and sex-related variation in physiological biomarkers is well documented, yet how coordinated systemic physiology unfolds across life stages at the population level remains unclear. Here, we introduce the Principal Component Life Trajectory (PCLT), reconstructing physiological trajectories via multivariate analysis of 54 blood-based biomarkers from 11,124 participants in the National Health and Nutrition Examination Survey (NHANES). Quantifying year-on-year progression with Euclidean Trajectory Distance (ETD), we identify five distinct phases in an unbiased manner: Early adolescence, Sexual Divergence, Sexual Convergence, Late Adulthood, and Advanced Aging. Trajectories show early, pronounced sexual divergence validated in an ethnically distinct, independent cohort. Chronic disease is associated with PCLT displacement and increased ETD progression, whereas metabolic, behavioral, and psychosocial factors generate graded, phase-specific perturbations. Together, these findings establish PCLT as a reproducible framework for characterizing structured physiological change across the lifespan and for monitoring population-level health dynamics.