{
  "abstract": "Background and Aims: Ageing is accompanied by progressive microvascular dysfunction, a key determinant of organ performance and longevity. The molecular drivers of this process remain incompletely defined, and the mechanisms by which exercise counters vascular ageing are unclear. This study investigated whether exercise-regulated long noncoding RNAs (lncRNAs) contribute to microvascular ageing and age-related cardiac dysfunction.\n\nMethods: RNA sequencing was performed in naturally aged mice with and without voluntary exercise. Functional studies of candidate lncRNAs were conducted using AAV-mediated overexpression, antisense oligonucleotides, and CRISPR-based knockdown, both in vivo and in endothelial cells (ECs).\n\nResults: A novel set of lncRNAs altered in hearts from exercised aged mice was identified and termed Senescence Associated LncRNA Transcripts in Exercise (SALTes). Among these, SALTe1 is evolutionarily conserved and enriched in ECs. SALTe1 expression is elevated in hearts from aged mice and in patients with various types of heart failure but suppressed by exercise. In 20-month-old mice, SALTe1 inhibition, via antisense GapmeRs or EC-specific deletion, attenuated endothelial senescence, restored microvascular perfusion, and improved diastolic function. Mechanistic studies showed that SALTe1 acts, at least in part, through upregulation of PARP9.\n\nConclusions: These findings establish SALTe1 as a pivotal regulator of endothelial senescence as well as microvascular and cardiac dysfunction in ageing. Targeted inhibition of SALTe1 recapitulates the vasculoprotective effects of exercise, highlighting a tractable antisense-based therapeutic strategy for combating age-related cardiac decline.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA",
    "Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA",
    "Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA",
    "Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA",
    "Stanley and Judith Frankel Institute for Heart and Brain Health, University of Michigan Medical Center, North Campus Research Complex, 2800 Plymouth Road, NCRC Building 25, Ann Arbor, MI 48109-2800, USA",
    "Chair for Gender Medicine, University of Zurich, Zurich 8006, Switzerland",
    "Department of Cardiology, University Hospital Zurich, Zurich 8091, Switzerland",
    "German Center for Heart and Cardiovascular Research (DZHK), Heidelberg, Germany",
    "Department of Cardiology, University Hospital Heidelberg, Heidelberg 69120, Germany",
    "Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Haobo Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiao Xiao"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Yirong Zhou"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yajing Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiayi Kang"
    },
    {
      "affs": [
        4
      ],
      "name": "Zixun Yuan"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiaqi He"
    },
    {
      "affs": [
        4
      ],
      "name": "Justin Guerra"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Carolin Lerchenmüller"
    },
    {
      "affs": [
        9
      ],
      "name": "Kenneth B. Margulies"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Aaron D. Aguirre"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jason D. Roh"
    },
    {
      "affs": [
        4
      ],
      "name": "Anthony Rosenzweig",
      "orcid": "0000-0001-6387-0386"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/23dhg14nhktbt.bib",
  "cited_by": 2,
  "doi": "10.1093/eurheartj/ehag356",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711036/",
  "id": "23dhg14nhktbt",
  "issns": [
    "0195-668X",
    "1522-9645"
  ],
  "landing_url": "https://doi.org/10.1093/eurheartj/ehag356",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2737|Telomeres, Telomerase, and Senescence"
    ]
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  "openalex": "W7161740686",
  "pdf_url": null,
  "pmcid": "PMC13711036",
  "pmid": "42155043",
  "published": "2026-05-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/23dhg14nhktbt.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:53Z",
      "native_id": "PMC13711036",
      "source": "pmc",
      "url": "https://doi.org/10.1093/eurheartj/ehag356"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Telomeres, Telomerase, and Senescence",
      "subfield": "physiology"
    }
  ],
  "title": "Long noncoding RNA SALTe1, microvascular ageing, and cardiac dysfunction",
  "title_text": "Long noncoding RNA SALTe1, microvascular ageing, and cardiac dysfunction",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:53Z",
  "url": "https://research.draconitic.com/paper/23dhg14nhktbt",
  "venue": "European heart journal",
  "versions": []
}