{
  "abstract": "Asparagine endopeptidase (AEP), also known as legumain, is a lysosomal cysteine protease whose activity increases with age and contributes to age-related tissue dysfunction. We tested whether chronic AEP inhibition could slow aging phenotypes in naturally aged mice. Here, we show that chronic treatment with the AEP inhibitor #11a extended lifespan and improved health span in aged C57BL/6 mice, together with reduced frailty and improved physical and cognitive performance. #11a treatment also attenuated several senescence- and inflammation-associated readouts in multiple organs. Mechanistically, #11a treatment suppressed AEP-dependent cleavage of nicotinamide phosphoribosyltransferase (NAMPT), accompanied by an increased NAD+/NADH ratio and higher SIRT1 levels. These findings support further investigation of pharmacological AEP inhibition as a strategy to promote healthy aging.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Menghan Yang"
    },
    {
      "name": "Xin Meng"
    },
    {
      "name": "Zhongyun Xie"
    },
    {
      "name": "Mengmeng Wang"
    },
    {
      "name": "Zhengjiang Qian"
    },
    {
      "name": "Keqiang Ye",
      "orcid": "0000-0002-7657-8154"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/77vk4ps544j17.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117990",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720683/?tool=EBI",
  "id": "77vk4ps544j17",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03373-0",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Animal physiology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "heading",
      "Biochemistry"
    ],
    [
      "heading",
      "Biological sciences"
    ],
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7223267586",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720683/pdf/?tool=EBI",
  "pmcid": "PMC13720683",
  "pmid": "42964811",
  "published": "2026-10-23",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/77vk4ps544j17.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.1016/j.isci.2026.117990",
      "source": "feed-cell",
      "url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03373-0"
    },
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1016/j.isci.2026.117990",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2589004226033730"
    },
    {
      "first_seen": "2026-10-31T12:21:37Z",
      "native_id": "PMC:PMC13720683",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13720683"
    },
    {
      "first_seen": "2026-11-03T12:21:31Z",
      "native_id": "PMC13720683",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.isci.2026.117990"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "Inhibition of asparagine endopeptidase extends the lifespan and improves health span during aging",
  "title_text": "Inhibition of asparagine endopeptidase extends the lifespan and improves health span during aging",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:31Z",
  "url": "https://research.draconitic.com/paper/77vk4ps544j17",
  "venue": "iScience",
  "versions": []
}