Preprint on 16 human organs identifies two partly independent dimensions of tissue aging

Preprint on 16 human organs identifies two partly independent dimensions of tissue aging

On September 13, the authors posted a preprint on bioRxiv analyzing 14 788 microscopic tissue sections from 16 organs in 980 deceased donors from GTEx, a project that collects human tissue samples. They identified approximately 3,5 billion cells in these sections and examined how cell numbers and spatial organization varied with age.

Tissue can be described in two ways: by counting cells of each type and by examining how they form functional structures, such as intestinal crypts, vascular niches, and connective tissue regions. This arrangement determines which cells touch one another and the structure of the tissue.

The same group had previously identified an age-related signal in microscopic GTEx tissue sections. This time, the authors started with individual cells, grouped neighboring cells, and identified recurring tissue regions that they termed functional units: crypts, vascular niches, and connective tissue regions.

They identified 236 types of functional units; the proportion of tissue sections occupied by 62 of these types varied with age. Densely packed regions containing specialized cells that carry out tissue functions tended to occupy smaller areas, while less dense regions containing connective tissue and immune cells tended to occupy larger areas. These comparisons were between deceased donors of different ages.

The authors tested whether these changes could be predicted solely from increases or decreases in the abundance of each cell type. For each functional unit, they calculated the expected age-related changes from changes in the density of its constituent cell types. These calculations explained only 7% of the variation in the observed changes (R² = 0,07).

In this sample, cell composition and spatial organization emerged as distinct measurable features of age-related tissue remodeling.