Aging unfolds in fixed phases across cell types

A large study analysed more than twenty million cells from various organs of mice at five different ages. The activity patterns of twenty thousand genes were measured in each cell. The researchers identified 536 main cell types and 1,828 subtypes. Only about a quarter of those subtypes changed strongly with aging; the rest remained stable throughout the lifespan.

Early loss, later expansion

In the earliest phase (equivalent to the human twenties and thirties), certain fat and muscle cells disappeared. Two immature brain cell types capable of regenerating tissue also declined early. Next, in a phase corresponding to the human thirties and forties, tissue-maintenance cells vanished: tendon cells (tenocytes), cells surrounding blood vessels, smooth muscle cells in the colon, and kidney epithelial cells.

Around the equivalent of human ages forty to fifty, the pattern shifted. Instead of cell loss, cell expansion followed. Immune cells increased, as did cells in lungs and kidneys whose properties had been altered by stress or inflammation. Transcriptional variation (the degree to which cells of the same type begin to function differently) increased with age.

What this tells us about aging as a process

The finding that aging proceeds through distinct time windows is relevant for how interventions are designed. If certain cells are most vulnerable at a specific life stage, targeted treatment at that point might be most effective. The researchers cautiously describe the process as a ‘coordinated remodelling of the society of cells’, but stress that the data are equally consistent with an accumulation of damage, not necessarily a fixed program.

The study was conducted in mice. Whether the same phases and cell types apply in humans requires further investigation.

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