Related Experiment Video
Updated: May 17, 2026

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
Aged circulating CD8+ T cells and their secreted factors drive cognitive decline
Juliana Sucharov1, Gregor Bieri2, Karishma J B Pratt3
1Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
Abstract:
Changes in peripheral CD8+ T cells are a hallmark of immune aging. However, the role of aged non-infiltrating CD8+ T cells in brain aging remains to be fully defined. Here, we showed that aged circulating CD8+ T cells and their secreted factors drove hippocampal-dependent cognitive decline. Using heterochronic parabiosis and transcriptomics analysis, we observed that peripheral CD8+ T cells maintained properties intrinsic to their age. Systemic exposure of young mice to aged CD8+ T cells elicited synaptic-related hippocampal changes and impaired cognition, and inhibiting activation, but not infiltration, mitigated their pro-aging effects. Conversely, targeting aged circulating CD8+ T cells restored youthful signatures and rescued cognition. Mechanistically, we identified granzyme K (GZMK) as a secreted pro-aging CD8+ T cell-derived factor in plasma, and GZMK inhibition rescued cognition in aged animals. Together, our data identified activated aged CD8+ T cell-derived circulating factors as potential therapeutic targets to rescue cognition in old age.
Related Concept Videos
Alzheimer Disease l: Introduction
Alzheimer Disease ll: Pathophysiology
Cognitive Development During Adulthood
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Dementia l: Introduction