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AGED CD8+ T CELLS DRIVE COGNITIVE DECLINE VIA GZMK

GSE266454 Mus musculus (mouse) Single-cell RNA-seq 21 samples Submitted 2026/06/25 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 21 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
21 samples: 6 × YT vs 5 × AT vs 5 × cd8a vs 5 × IGGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Aged circulating CD8(+) T cells and their secreted factors drive cognitive declineImmunity · 2026
Summary (written by the submitters)
Changes in peripheral CD8+ T cells are a prominent hallmark of immune aging. While infiltrating CD8+ T cells are implicated in aging and neurodegenerative disease-related pathology in the brain, the role of aged non-infiltrating CD8+ T cells has yet to be fully defined. Here, we show that targeting activated aged peripheral CD8+ T cells rescues age-related cognitive decline.
Read the full summary ↓
Using heterochronic parabiosis and single cell transcriptomics analysis we observed that aged peripheral CD8+ T cells maintain properties intrinsic to their age, being refractory to the effects of a young or aged systemic milieu. Systemic exposure of young mice to aged CD8+ T cells elicited synaptic-related aging transcriptional signatures in the hippocampus and impaired cognition. Inhibiting migration of aged peripheral CD8+ T cells to lymph nodes mitigated pro-aging effects on the young hippocampus. Conversely, targeting aged CD8+ T cells restored synaptic-related signatures in the aged hippocampus and ameliorated cognitive impairments. Mechanistically, we identified granzyme k (GZMK) as a secreted age-associated CD8+ T cell-derived factor that impairs cognitive function. Together, our data identify activated aged CD8+ T cells and their secreted factors as potential therapeutic targets to rescue cognition in old age.
Published in
Aged circulating CD8(+) T cells and their secreted factors drive cognitive decline
Sucharov J, Bieri G, Pratt KJB et al. · Immunity 2026 · PMID 42140192 · doi:10.1016/j.immuni.2026.04.014
This dataset
Open GSE266454 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE266454_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1107204 and SRA study SRP505409. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42140192) ↗
Study design
6 × YT vs 5 × AT vs 5 × cd8a vs 5 × IG

Supports a between-group comparison across 21 samples.

How we read this: 4 replicated groups read from 21 sample titles; they account for 21 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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