Aged circulating CD8+ T cells and their secreted factor granzyme K drive cognitive decline in mice
By
Saul A. Villeda1,2,3,4,6,7,8 Send email to [email protected]
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Summary
This study investigates how aged circulating CD8+ T cells contribute to cognitive decline without infiltrating the brain. Using heterochronic parabiosis and transcriptomics in mice, researchers found that aged CD8+ T cells maintain age-intrinsic properties and their secreted factors (particularly granzyme K) drive hippocampal-dependent cognitive impairment. Exposing young mice to aged CD8+ T cells caused synaptic changes and cognitive deficits. Crucially, removing aged T cells or blocking granzyme K rescued cognitive function, suggesting potential therapeutic targets for age-related cognitive decline through immune factors in circulation.
Key quotes
· 4 pulledSucharov et al. reveal that aged circulating cytotoxic T cells are drivers of age-related cognitive decline.
Removal of aged T cells, or their secreted factor granzyme K, rescues cognition in mice.
These findings have promise for therapeutics that target immune factors in circulation to restore brain function.
Systemic exposure of young mice to aged CD8+ T cells elicited synaptic-related hippocampal changes and impaired cognition.
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