🧬 Aging Wiki

2026-08-31

3 min read

2026-08-31

Ingest + verify — PAI-1/SERPINE1 aging evidence from a YouTube lead

Reviewed the YouTube video “PAI-1 Impacts Telomere Length, Cell Senescence, And Longevity” under scraping-youtube-references. The video description contained promotions and no scientific references, so its transcript was used only to identify claims. No wiki claim cites the video; each incorporated claim was mapped to and checked against primary literature.

Pages added and independently verified

  • pai-1 — canonical SERPINE1/PAI-1 protein page. The evidence supports a window-sensitive target: partial lifelong deficiency is associated with favorable metabolic, vascular, telomere, and survival phenotypes, whereas complete deficiency causes delayed bleeding and is associated with cardiac fibrosis. Aging-context druggability is tier 1 because TM5614 reached an aging-focused human study, but no controlled peer-reviewed human geroscience efficacy result exists.
  • khan-2017-serpine1-longevity — 177-person founder-cohort study plus extended-pedigree survival analysis (doi:10.1126/sciadv.aao1617). Verified the approximately 10% longer age-adjusted LTL, 28% lower fasting insulin, 0/43 versus 8/127 diabetes comparison, and 85-versus-75-year median survival. The age-associated LTL slope did not differ, and only 56 of 221 relatives with known lifespan had direct or obligate genotype ascertainment.
  • khoddam-2025-pai1-aortic-aging — human cfPWV comparison and mouse perturbation series (doi:10.1172/JCI196714). Verified the adjusted human effect (−1.182 m/s), exact mouse median-survival change (749 to 875 days; 16.8%, reported as 17%), and the boundary that TM5614 restored PWV but not systolic or diastolic pressure to baseline during continued l-NAME exposure. Source-data/reporting inconsistencies are documented on the study page.

Claims corrected or not incorporated

  • “Almost 20%” mouse lifespan extension was replaced with the paper’s reported 17% median-survival increase.
  • “Nearly 100 carriers, only one diabetes case” was not found in the published cohort; the verified 2017 comparison is 0/43 heterozygotes versus 8/127 noncarriers.
  • “Preserved juvenile epigenetic patterns” was not matched to a published primary study and was not incorporated.
  • DNAm PAI-1 in GrimAge is a 211-CpG methylation surrogate, not a plasma PAI-1 assay. It was the strongest individual protein-surrogate lifespan signal, but DNAm pack-years and the final GrimAge composite were stronger predictors.
  • The proposed direct PAI-1→PD-L1 senescent-cell immune-evasion chain was not incorporated as established aging biology. Direct PAI-1/PD-L1 evidence located was in tumor models, while senescent-cell PD-L1 evidence does not establish PAI-1 as its upstream cause.
  • “Perfect replication” across species was rejected: the CRISPR mouse model reproduces the allele and several directional phenotypes, but the human evidence remains one related founder population and the drug-reversal model used l-NAME stress rather than natural aging.

Propagation

  • telomere-length-leukocyte — added the SERPINE1 natural experiment with the critical LTL-level-versus-attrition-slope distinction.
  • arterial-stiffening — added the verified human cfPWV effect, mouse perturbation evidence, TM5614 boundary, and complete-deficiency safety context.
  • pcsk9 — added the bounded PAI-1→PCSK9 edge from mouse genetics/pharmacology and a small human plasma comparison.
  • grimage-2019 — corrected the relative ranking and direct-assay-versus-DNAm-surrogate distinction.
  • sasp, apoptosis-pathway, and acronyms — resolved existing PAI-1 mentions to the new atomic page.

Independent verifier passes checked the new pages against complete primary articles and available supplements/supporting data, searched for corrections/retractions/supersession, and promoted all three pages to verified: true on 2026-08-31.

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