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Senescence-associated β-galactosidase reveals the abundance of senescent CD8+ T cells in aging humans
Aging Cell. 2021 May 3;e13344. doi: 10.1111/acel.13344.
Ricardo I Martínez-Zamudio 1 2, Hannah K Dewald 3 4 5, Themistoklis Vasilopoulos 1 2 3, Lisa Gittens-Williams 6, Patricia Fitzgerald-Bocarsly 4 5, Utz Herbig 1 2
Abstract:
...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 60s. 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.