{
  "abstract": "Aging clocks and biomarkers are increasingly used as if they were the mechanism that drives mortality. But a mechanism, unlike a thermometer, must satisfy three conditions: it must account for the mortality signal, be causal, and be the layer that reverses when aging is reversed. Using public or provider-restricted de-identified data, we test all three. First (accounting), a Markov generator-matrix model with death as an absorbing state, fitted jointly to biomarkers and mortality in NHANES (n=23,512) and replicated in the Health and Retirement Study, assigns most of the Gompertz rise in mortality to a component latent to measured blood biomarkers (92.7%; 89.1% under a mean-field re-specification; 91.5% on replication). Second (causation), a positive-control-calibrated, two-platform cis-pQTL Mendelian-randomization design (UKB-PPP, deCODE) detects known causal proteins (LPA, IL6R) yet finds the measurable inflammatory, renal and growth-signalling markers null. Third (reversibility), at donor level reprogramming reverses a chronological clock (-9.7 and -22.4 yr), whereas a causality-enriched damage clock shows no detectable reversal while somatic identity is retained and moves only as pluripotency is approached. On these data the biomarkers meet none of the three conditions; aging measures appear to track mortality risk rather than its cause, a caution for their use as surrogate end-points.",
  "abstract_shown": true,
  "affiliations": [
    "Oita University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. Tanigawa"
    },
    {
      "name": "T. Iwaki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7j3dd3ajxfy04.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.07.05.26356402",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.07.05.26356402v2.full",
  "id": "7j3dd3ajxfy04",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.07.05.26356402v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "geriatric medicine"
    ],
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7167834878",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.07.05.26356402v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7j3dd3ajxfy04.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:50Z",
      "native_id": "10.64898/2026.07.05.26356402",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.07.05.26356402v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "A generator-matrix model quantifies the limited contribution of measured biomarkers to human mortality acceleration",
  "title_text": "A generator-matrix model quantifies the limited contribution of measured biomarkers to human mortality acceleration",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:50Z",
  "url": "https://research.draconitic.com/paper/7j3dd3ajxfy04",
  "venue": "medRxiv",
  "versions": []
}