{
  "abstract": "Maintenance of neuronal function during aging requires metabolic adaptation, yet how metabolite-sensitive chromatin regulators contribute to this process remains unclear. YEATS-domain proteins, including ENL and AF9, recognize histone acylation marks and are positioned at the interface between cellular metabolism and transcriptional regulation. We previously showed that pan-neuronal suppression of dENL/AF9, the single Drosophila orthologue of mammalian ENL and AF9, extends lifespan, preserves healthspan, and enhances oxidative-stress resistance. Here, we used multi-omics and biochemical analyses to define the molecular state associated with neuronal dENL/AF9 suppression. Transcriptomic profiling revealed a markedly stronger response in aged than young male fly heads, with prominent enrichment of fatty-acid degradation and several intermediary metabolic pathways in the aged dataset. Guided by this age-related transcriptional response, we focused subsequent profiling on aged heads, where independent molecular layers converged on a distinct metabolic and energetic signature. Lipidomics identified reduced abundance of multiple triglyceride-related and fatty acid derivatives, while metabolomics revealed changes in central-carbon/TCA-, nicotinamide-, and purine-associated features. Proteomics implicated mitochondrial and ATP-associated processes, accompanied by increased ATP abundance and a higher NAD/NADH ratio. Matched lipidome-metabolome integration further identified citrate as a cross-omics feature inversely associated with altered triglyceride and ceramide species, linking central-carbon and lipid-associated components of the molecular signature. Together, these findings identify a stronger transcriptional response to neuronal dENL/AF9 suppression in aged flies and a distinct metabolic and energetic molecular signature in aged fly heads, providing candidate molecular correlates of the previously established longevity phenotype and a framework for studies of neuronal aging biology.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Medicine, ChiangMai University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "R. Yeewa"
    },
    {
      "name": "P. Noisagul"
    },
    {
      "name": "S. Dissook"
    },
    {
      "name": "C. Panto"
    },
    {
      "name": "P. Poound"
    },
    {
      "name": "S. JANTRAPIROM"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Lo Piccolo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ebjpabnsdkffj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.30.755827",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755827v1.full",
  "id": "ebjpabnsdkffj",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755827v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7216282160",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755827v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ebjpabnsdkffj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:46Z",
      "native_id": "10.64898/2026.09.30.755827",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755827v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Multi-omics profiling identifies a metabolic and energetic signature associated with neuronal dENL/AF9 suppression in aged flies",
  "title_text": "Multi-omics profiling identifies a metabolic and energetic signature associated with neuronal dENL/AF9 suppression in aged flies",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:46Z",
  "url": "https://research.draconitic.com/paper/ebjpabnsdkffj",
  "venue": "bioRxiv",
  "versions": []
}