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Series GSE169009 Query DataSets for GSE169009
Status Public on Apr 14, 2021
Title Senescence‐associated β‐galactosidase reveals the abundance of senescent CD8+ T cells in aging humans
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Aging leads to a progressive functional decline of the immune system, rendering the elderly increasingly susceptible to disease and infection. The degree to which immune cell senescence contributes to this decline remains unclear, however, since markers that label immune cells with classical features of cellular senescence accurately and comprehensively have not been identified. Using a second‐generation fluorogenic substrate for β‐galactosidase and multi‐parameter flow cytometry, we demonstrate here that peripheral blood mononuclear cells (PBMCs) isolated from healthy humans increasingly display cells with high senescence‐associated β‐galactosidase (SA‐βGal) activity with advancing donor age. The greatest age‐associated increases were observed in CD8+ T‐cell populations, in which the fraction of cells with high SA‐βGal activity reached average levels of 64% in donors in their 60 s. CD8+ T cells with high SA‐βGal activity, but not those with low SA‐βGal activity, were found to exhibit features of telomere dysfunction‐induced senescence and p16‐mediated senescence, were impaired in their ability to proliferate, developed in various T‐cell differentiation states, and had a gene expression signature consistent with the senescence state previously observed in human fibroblasts. Based on these results, we propose that senescent CD8+ T cells with classical features of cellular senescence accumulate to levels that are significantly higher than previously reported and additionally provide a simple yet robust method for the isolation and characterization of senescent CD8+ T cells with predictive potential for biological age.
Overall design We performed bulk RNA-seq of FACS-isolated CD8+T cells exhibiting low and high senescence associated ß-galactosidase activity.
Contributor(s) Martínez-Zamudio RI, Dewald HK, Vasilopoulos T, Gittens-Williams L, Fitzgerald-Bocarsly P, Herbig U
Citation(s) 33939265
Submission date Mar 16, 2021
Last update date Jul 14, 2021
Contact name Ricardo Iván Martínez Zamudio
Organization name Rutgers Biomedical and Health Sciences | Rutgers-Robert Wood Johnson Medical School
Department Pharmacology
Lab Martínez Zamudio Lab
Street address 675 Hoes Lane West
City Piscataway
State/province New Jersey
ZIP/Postal code 08854
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM5173898 SAßGal low, young donor #1
GSM5173899 SAßGal low, young donor #2
GSM5173900 SAßGal low, young donor #3
BioProject PRJNA714897
SRA SRP310876

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Supplementary file Size Download File type/resource
GSE169009_counts_and_rld_per_gene.txt.gz 2.3 Mb (ftp)(http) TXT
GSE169009_rld_LFC_DEGs.txt.gz 469.4 Kb (ftp)(http) TXT
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