PathStAR mapped the ages at which human tissue structure changes most rapidly

PathStAR mapped the ages at which human tissue structure changes most rapidly

On August 31, Nature Aging published a study of PathStAR, a method that compares digital scans of stained tissue sections and measures the rate at which their structure changes. The authors analyzed 25 306 images of 40 tissue types from 970 deceased donors aged 21 to 70 years.

A different model trained on the same tissue sections estimated each donor's chronological age. PathStAR identifies the ages at which the structure of a specific tissue changes more rapidly.

The team used GTEx, a collection of tissues obtained from deceased donors. They divided the tissue scans into patches, converted visible structural features into sets of numbers, and compared these sets between adjacent ten-year age groups while shifting the group boundaries by one year at a time. This produced a curve showing the rate of structural change in each tissue.

The analysis yielded reliable trajectories for 15 tissues. Arteries changed most rapidly during the donors' 30s. The rate increased in the uterus and vagina during the early and mid-50s, close to menopause. Digestive tissues, the prostate, and the testes showed two increases, one around age 30 and another around age 50. When the researchers repeated the analysis using three other algorithms for tissue section analysis, the overall pattern remained consistent for most tissues.

The authors compared these age-related peaks with GTEx gene activity data. During periods of rapid structural change, tissues showed a shared increase in inflammatory programs and reduced activity in programs related to energy production, cell division, and intracellular quality control. The authors also measured how much each donor's tissue structure differed from the pattern typical for that donor's age. These differences were correlated across the digestive, vascular, and reproductive systems. Within the same person, they were more likely to point in the same direction.

“Because tissue structure underlies tissue function, structural aging provides a more interpretable link to functional decline than molecular approaches alone,” the authors write.

This map makes it possible to test interventions with a specific question: do they preserve the structure of a selected tissue during a period of rapid change?