Mouse aging atlases revealed how tissues change the composition of their cell populations during different age windows
Mouse aging atlases revealed how tissues change the composition of their cell populations during different age windows
On August 14, Quanta Magazine published an interview with cell biologist Junyue Cao about two mouse aging atlases. These atlases show how the proportions of different cell populations in tissues change with age and which signals accompany those transitions.
A tissue contains cells with different roles. Some support blood vessels and tendons, others participate in immune responses, and still others repair damage. The proportions of these cells change with age. Cao studies which populations shrink or expand during each age window and which signals are associated with those transitions.
Cao began working on this problem while searching for molecular targets that might slow aging. Many molecular pathways are associated with age, but their effects depend on the cell type. His group developed EasySci, a method that identifies active genes in the nuclei of individual cells. This set of genes can be used to identify the cell type and measure how its proportion within a tissue changes.
The PanSci atlas included 21 786 931 nuclear profiles from more than 600 samples across 14 tissues, collected from mice of both sexes between three and 23 months of age. All samples were processed using the same protocol so that differences between data batches would not be mistaken for age-related changes. The authors identified more than 200 cell populations whose proportions within tissues changed substantially with age. Some populations declined, whereas others expanded, and these shifts occurred during different age windows.
“The changes that occur during aging do not affect all cells equally,” Cao says.
In a separate experiment, the researchers selectively removed mature lymphocytes, which are a subset of immune cells, from adult and old mice and examined how other populations changed. Some age-related expansions depended on these cells. This experiment tested one pathway through which one group of cells affects another.
In the second study, the group mapped chromatin accessibility, which indicates which regions of DNA in the nucleus are available for gene transcription. The map covered 21 tissues from mice of both sexes in three age groups. About a quarter of the 536 cell types and 1 828 more narrowly defined subtypes changed substantially with age. The authors linked coordinated shifts in cell types found across many tissues to intrinsic regulators of gene activity and to cytokine programs, which involve signaling molecules that cells use to communicate with one another.
“Molecular changes, and possibly other changes associated with aging, converge on a reorganization of the cellular community,” Cao says.
These atlases divide the broad question of aging into testable questions: which cell population changes during a specific period, and which signal is associated with that change.