{
  "abstract": "Introduction: Cellular senescence in human T cells remains incompletely defined, particularly with respect to how senescence-associated states influence susceptibility to cell death.\n\nMethods: We used flow-cytometric SPiDER-based detection of senescence-associated β-galactosidase (SA-β-Gal) activity to profile human CD8+ T-cell subsets from young and old donors. We stratified effector memory (CD8 EM ) and effector memory re-expressing CD45RA (CD8 EMRA ) subsets by the lowest (bottom 25%) and highest (top 25%) quartiles of SA-β-Gal signal.\n\nResults: CD8 EM and CD8 EMRA cells displayed the greatest within-subset heterogeneity in SA-β-Gal activity. The SA-β-Gal low and high populations occupied distinct regions in UMAP projections and were reproducibly enriched in different FlowSOM metaclusters, indicating that SA-β-Gal activity captures structured phenotypic states within differentiated CD8+ T-cell compartments. These states differed in senescence-associated markers, including CD27, CD28, CD57, and CX3CR1, as well as granzyme-associated programs involving Gzm A, B and K, whereas chronological age had only a limited effect once subsets were analyzed separately. Functionally, nutrient-limited conditions unmasked marked differences in cell death susceptibility between these populations. Following PMA/ionomycin stimulation, SA-β-Gal high CD8 EM and CD8 EMRA cells underwent accelerated stimulation-induced cell death, showed increased caspase-3/7 activation, and exhibited lower post-treatment γH2AX signal relative to SA-β-Gal low counterparts. In contrast, in the absence of stimulation-induced energetic demand, SA-β-Gal high cells displayed greater resistance to cell death.\n\nDiscussion: Together, SA-β-Gal stratification resolves structured heterogeneity within human CD8 effector T cells and supports a context-dependent model in which senescence-associated effector states become selectively vulnerable to stimulation-induced death under metabolic stress.",
  "abstract_shown": true,
  "affiliations": [
    "Rutgers School of Graduate Studies, Rutgers Biomedical and Health Sciences, Rutgers University",
    "Department of Pathology, Immunology, and Laboratory Medicine, Rutgers-New Jersey Medical School",
    "Department of Microbiology, Biochemistry and Molecular Genetics, Center for Cell Signaling, Rutgers-New Jersey Medical School"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Luis Garza-Martínez"
    },
    {
      "affs": [
        0
      ],
      "name": "Mark Apadeer"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nica Mariz Aquino"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Paolo S. Turano"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Elizabeth Akbulut"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Dillon Oswald"
    },
    {
      "affs": [
        1
      ],
      "name": "Sukhwinder Singh"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Patricia Fitzgerald-Bocarsly"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1epehy6k1j7bg.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1985303",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1985303/full",
  "id": "1epehy6k1j7bg",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1985303/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC581-607"
    ],
    [
      "openalex",
      "2737|Telomeres, Telomerase, and Senescence"
    ]
  ],
  "openalex": "W7223648595",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1985303/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1epehy6k1j7bg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1985303",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1985303/full"
    },
    {
      "first_seen": "2026-10-30T13:47:30Z",
      "native_id": "7a5b284b42534928af4488a82438e5e4",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fimmu.2026.1985303"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Telomeres, Telomerase, and Senescence",
      "subfield": "physiology"
    }
  ],
  "title": "SA-β-Gal stratification reveals senescence-associated heterogeneity and differential cell death susceptibility in human CD8 effector T cells",
  "title_text": "SA-β-Gal stratification reveals senescence-associated heterogeneity and differential cell death susceptibility in human CD8 effector T cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:30Z",
  "url": "https://research.draconitic.com/paper/1epehy6k1j7bg",
  "venue": "Frontiers in Immunology",
  "versions": []
}