{
  "abstract": "The aging process is driven by parallel accumulation of damage across multiple molecular “counters”—telomeric (#2), centriolar (#1), mitochondrial (#3), epigenetic (#4), and proteostatic (#5). The Multi-Counter Organismal Aging (MCOA) framework posits that no single counter universally limits lifespan; instead, their relative contribution depends on tissue context. Here we extend MCOA with three interconnected principles and introduce piRNA-mediated regulation as a potential sixth counter (#6). First, we formalize context-dependent counter prioritization through a nonlinear differential equation incorporating damage clearance. Second, we provide an updated atlas of tissue-specific winner counters, demonstrating that hematopoietic stem cells (HSCs) can switch from telomeric (#2) to proteostatic (#5) dominance under inflammatory stress, as observed in VEXAS syndrome . Third, we propose the Master-Counter Hypothesis: organismal aging is governed by winner counters operating within tissue-specific stem cell compartments. Using a meta-analysis of 28,325 participants (Global Epigenetic Age Consortium, The Lancet Healthy Longevity, 2025), we demonstrate that GrimAge epigenetic age acceleration (EAA) has the strongest association with frailty (β=0.11, 95% CI 0.06–0.15) and serves as an integrative marker of the master counter . Finally, we introduce piRNA-mediated regulation as a potential counter #6: circulating piRNAs predict 2-year survival with AUC up to 0.92 in older adults, and lower piRNA levels associate with longer survival . Nine piRNAs were identified as potential therapeutic targets. We present falsifiable predictions, including tissue-specific proteostasis interventions and piRNA-targeted therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Georgia Longevity Alliance, Reg. №404506520"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jaba Tkemaladze",
      "orcid": "0000-0001-8651-7243"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b3fevt9ze3fhn.bib",
  "cited_by": 35,
  "doi": "10.65649/n15sg225",
  "fulltext_url": null,
  "id": "b3fevt9ze3fhn",
  "issns": [
    "3088-4063"
  ],
  "landing_url": "https://doi.org/10.65649/n15sg225",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7160713260",
  "pdf_url": "https://longevity.ge/longhoriz/article/download/179/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b3fevt9ze3fhn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7160713260",
      "source": "openalex",
      "url": "https://doi.org/10.65649/n15sg225"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "A Stem-cell-centric Multi-counter Theory of Organismal Aging",
  "title_text": "A Stem-cell-centric Multi-counter Theory of Organismal Aging",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T13:20:46Z",
  "url": "https://research.draconitic.com/paper/b3fevt9ze3fhn",
  "venue": "Longevity Horizon",
  "versions": []
}