Eight-year study reveals how molecular aging scripts differ individually

Aging does not appear to follow the same molecular script for everyone, according to an eight-year study of 335 women. The findings reveal that individual molecular trajectories of aging can diverge substantially from population-wide patterns and are shaped not only by genetics but also by factors such as circadian rhythm, seasonality, and environmental exposures.

"Understanding of such individual variation in longitudinal trajectories will be crucial for precision medicine approaches in the future," say the study's authors. Multiomic profiles – broad measurements of genes, metabolites, and other biological signals – offer a detailed snapshot of an individual's physiological state at the molecular level and could help to detect disease risk earlier and tailor interventions more precisely. Realizing this potential, however, requires distinguishing the normal molecular changes of aging from those associated with disease. Although researchers have mapped molecular changes associated with aging in model organisms, comparable longitudinal data in humans have remained elusive.

To address this gap, Julia El-Sayed Moustafa and colleagues created the MultiMuTHER study using data from the long-running TwinsUK cohort. The MultiMuTHER study followed 335 female twins for up to eight years, collecting repeated measurements of whole-blood gene expression and 1,197 serum metabolites. Using this new longitudinal dataset, El-Sayed Moustafa et al. investigated which genes and metabolites changed over time, how these changes varied among cell types, and how genetics, seasonal cycles, time of day, and environmental pollutants such as PFAS (per- and polyfluoroalkyl substances) influenced molecular activity. They also explored how patterns of gene expression and metabolism are linked both at a single point in time and across the course of aging.

According to their findings, aging is accompanied by widespread but highly individual changes in the body's molecular landscape. Over a median of six years, more than 5,000 genes and 181 metabolites changed over time, including many associated with age-related diseases like cardiometabolic and neurodegenerative disorders. This suggests that people of the same chronological age can follow markedly different biological aging trajectories. The findings also revealed a complex remodeling of the immune system during aging, with signs of declining adaptive immune function alongside sustained or increasing activity in parts of the innate immune system, potentially contributing to chronic inflammation in later life. Moreover, the authors found that environmental exposures also left detectable, time-sensitive molecular signatures.