Human tissue is like a city: dense neighborhoods of specialized cells, streets of blood vessels, plazas of functional units. As we age, this city gets remodeled. Researchers from the GTEx project examined 14,788 tissue sections from 980 donors and segmented 3.5 billion cells across 16 organs to see how this architecture changes.

It turned out that cell density declines in 8 of 16 organs, most dramatically in the ovary (by 47%), lung (35%), and liver (27%). Epithelial cells, which line organ surfaces, suffer more than others. In the ovary, granulosa cells nearly disappear (a 45% drop per decade), in the lung, alveolar cells are lost (25-30% per decade), while in the pancreas, glandular columnar cells actually increase (+17% per decade).

But the main discovery concerns not cells but functional tissue units (FTUs): groups of cells that perform a specific job, such as crypts in the intestine or follicles in the ovary. Of the 236 FTUs analyzed, 62 change significantly with age. Dense, specialized structures are replaced by sparse and heterogeneous ones, enriched in stromal and immune cells. It's like neighborhoods with clear planning turning into chaotic suburbs.

The vascular network of the gastrointestinal tract thins out: in the small intestine, arteries lose 20% of their density per decade, veins and lymphatic vessels lose 15%. Cell morphology changes too: in the uterus, all three major populations undergo significant remodeling, and in the thyroid, despite stable density, there is the greatest remodeling (25-28% of features).

The work creates a quantitative atlas of cellular and architectural aging. It can serve as a reference for diagnosing age-related changes in pathology and for evaluating the effectiveness of anti-aging interventions. Aging remodels the city of our tissues, and now we have a map of those changes.

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