{
  "abstract": "Mitochondria are increasingly recognized as master regulators of aging, integrating bioenergetics, redox control, stem cell fate, and innate immune signaling. This review synthesizes evidence that mitochondrial dysfunction is not only a hallmark but also an upstream driver of stem cell exhaustion and inflammaging. We discuss how age-associated mitochondrial DNA (mtDNA) mutations and clonal mosaicism impair respiration and reshape metabolite availability, thereby reprogramming long-lived epigenetic states that govern quiescence, lineage commitment, and regenerative output. In parallel, erosion of mitochondrial quality control (MQC), including fission-fusion balance, mitophagy, and the mitochondrial unfolded protein response (UPRmt), permits the persistence of reactive oxygen species (ROS)-producing organelles and lowers containment of mitochondrial danger signals. A central advance is that mitochondrial damage can be decoded as inflammation: cytosolic mtDNA and other mitochondrial damage-associated molecular patterns (mtDAMPs) activate cGAS-STING and NF-κB pathways, reinforcing senescence-linked cytokine circuits and chronic inflammatory tone. We further highlight nicotinamide adenine dinucleotide (NAD⁺) depletion as a metabolic bottleneck that compromises sirtuin-dependent resilience and can enforce mitochondrial dysfunction-associated senescence (MiDAS), linking redox collapse to altered senescence phenotypes and regenerative decline. Finally, we evaluate emerging mitochondria-targeted rejuvenation strategies, NAD⁺ repletion, mitophagy enhancers, mitochondrial transplantation/engineering, and precision elimination of mutant mtDNA using mitochondria-targeted transcription activator-like effector nucleases (mitoTALENs) or zinc-finger nucleases (mitoZFNs), emphasizing tissue-specific thresholds and context dependence for effective healthspan extension.",
  "abstract_shown": true,
  "affiliations": [
    "Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador",
    "Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador. aalc84@gmail.com"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jhommara Bautista",
      "orcid": "0000-0002-9717-8096"
    },
    {
      "affs": [
        1
      ],
      "name": "Andrés López-Cortés",
      "orcid": "0000-0003-1503-1929"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bsnwmaj8jetwb.bib",
  "cited_by": 7,
  "doi": "10.1038/s41514-026-00422-5",
  "fulltext_url": null,
  "id": "bsnwmaj8jetwb",
  "issns": [
    "2731-6068"
  ],
  "landing_url": "https://doi.org/10.1038/s41514-026-00422-5",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7162665327",
  "pdf_url": "https://www.nature.com/articles/s41514-026-00422-5_reference.pdf",
  "pmcid": "PMC13500825",
  "pmid": "42209503",
  "published": "2026-05-28",
  "publisher": "Springer Science+Business Media",
  "ris": "https://research.draconitic.com/paper/bsnwmaj8jetwb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W7162665327",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41514-026-00422-5"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Mitochondrial Function and Pathology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mitochondrial drivers of stem cell aging and inflammaging",
  "title_text": "Mitochondrial drivers of stem cell aging and inflammaging",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T13:20:30Z",
  "url": "https://research.draconitic.com/paper/bsnwmaj8jetwb",
  "venue": "npj Aging",
  "versions": []
}