{
  "abstract": "NRF2 (Nuclear Factor Erythroid 2-Related Factor 2) has traditionally been viewed as a master regulator of the antioxidant response. However, emerging evidence redefines NRF2 as a pleiotropic and evolutionarily conserved systems-level integrator of redox, metabolic, proteostatic, and inflammatory homeostasis, i.e., an evolutionarily conserved guardian of health. From its origins as an adaptive response to rising atmospheric oxygen in early metazoans to its role in orchestrating complex cytoprotective networks in humans, NRF2 exemplifies the biological transition from stress resistance to adaptive resilience. Understanding its regulation across species, tissues, life stages and gender offers novel perspectives for combating age-related cellular dysfunction and reframing the dynamic process of redox regulation as a component of adaptive homeostasis in a precision medicine perspective. This review summarizes and integrates essential concepts currently being developed regarding the evolutionary roots of NRF2, its molecular and regulatory complexity, its dualistic role in health and disease, and its potential as a biomarker of resilience and therapeutic target. We highlight NRF2's function as a rheostat rather than a binary stress switch, including the role of hormetic activation through lifestyle and environmental stimuli. By maintaining redox homeostasis and dynamic adaptive stress responses, NRF2 bridges molecular defense mechanisms with strategies for healthspan extension and preventive medicine from very early life stages until senescence.",
  "abstract_shown": true,
  "affiliations": [
    "iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Lisboa, Portugal. Electronic address: stenreiro@nms.unl.pt",
    "iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Lisboa, Portugal",
    "Institute of Evolutionary Medicine, University of Zurich, Zurich, Switzerland",
    "Centre of Experimental Medicine, Slovak Academy of Sciences, Institute of Normal and Pathological Physiology, Bratislava, Slovakia",
    "Center for Behavioral Sciences and Mental Health, Instituto Superiore di Sanità, Rome, Italy",
    "Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain",
    "Center for Behavioral Sciences and Mental Health, Instituto Superiore di Sanità, Rome, Italy; Faculty of Medicine and Surgery, Catholic University of the Sacred Heart, Rome, Italy",
    "Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Krakow, Poland",
    "Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria",
    "Malopolska Centre of Biotechnology, Jagiellonian University in Krakow, Krakow, Poland",
    "Institute of Pharmaceutical Science, King's College London, London, United Kingdom; Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil",
    "Faculty of Medicine, University Hospital Bern, Switzerland",
    "Vienna Airway Lab, Department of Otolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria",
    "Department of Physiology and Pharmacology \"Vittorio Erspamer\", La Sapienza University, Rome, Italy",
    "International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland",
    "Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland",
    "Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sandra Tenreiro",
      "orcid": "0000-0001-7272-5842"
    },
    {
      "affs": [
        1
      ],
      "name": "Ana S. Falcão",
      "orcid": "0000-0002-4491-7457"
    },
    {
      "affs": [
        2
      ],
      "name": "Nicole Bender",
      "orcid": "0000-0002-3838-587X"
    },
    {
      "affs": [
        3
      ],
      "name": "Iveta Bernátová",
      "orcid": "0000-0002-6120-706X"
    },
    {
      "affs": [
        4
      ],
      "name": "Alessandra Berry",
      "orcid": "0000-0001-6562-9043"
    },
    {
      "affs": [
        5
      ],
      "name": "Antonio Cuadrado",
      "orcid": "0000-0002-4039-7140"
    },
    {
      "affs": [
        2
      ],
      "name": "Patrick Eppenberger",
      "orcid": "0000-0002-9526-8709"
    },
    {
      "affs": [
        6
      ],
      "name": "Letizia Giona",
      "orcid": "0009-0008-0093-5080"
    },
    {
      "affs": [
        7
      ],
      "name": "Anna Grochot‐Przeczek",
      "orcid": "0000-0003-0533-7254"
    },
    {
      "affs": [
        8
      ],
      "name": "Elke H. Heiß",
      "orcid": "0000-0001-7618-5505"
    },
    {
      "affs": [
        9
      ],
      "name": "Monika A. Jakubowska",
      "orcid": "0000-0002-4899-2606"
    },
    {
      "affs": [
        10
      ],
      "name": "Paul F. Long",
      "orcid": "0000-0001-6698-4602"
    },
    {
      "affs": [
        2
      ],
      "name": "Asya Makhro",
      "orcid": "0009-0001-5383-1110"
    },
    {
      "affs": [
        11
      ],
      "name": "Mojgan Masoodi",
      "orcid": "0000-0001-9840-1731"
    },
    {
      "affs": [
        12
      ],
      "name": "Christina Morgenstern",
      "orcid": "0000-0003-2943-9634"
    },
    {
      "affs": [
        13
      ],
      "name": "Luciano Saso",
      "orcid": "0000-0003-4530-8706"
    },
    {
      "affs": [
        1
      ],
      "name": "Miguel C. Seabra",
      "orcid": "0000-0002-6404-4892"
    },
    {
      "affs": [
        14
      ],
      "name": "Alicja Sznarkowska",
      "orcid": "0000-0002-9461-1878"
    },
    {
      "affs": [
        15
      ],
      "name": "Gerasimos Sykiotis"
    },
    {
      "affs": [
        16
      ],
      "name": "Ioannis P. Trougakos",
      "orcid": "0000-0002-6179-2772"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b3806mp07nd8z.bib",
  "cited_by": 9,
  "doi": "10.1016/j.redox.2026.104217",
  "fulltext_url": null,
  "id": "b3806mp07nd8z",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://doi.org/10.1016/j.redox.2026.104217",
  "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|Genomics, phytochemicals, and oxidative stress"
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  "openalex": "W7161300567",
  "pdf_url": null,
  "pmcid": "PMC13208080",
  "pmid": "42155153",
  "published": "2026-05-15",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/b3806mp07nd8z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
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      "url": "https://doi.org/10.1016/j.redox.2026.104217"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics, phytochemicals, and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "NRF2 as a guardian of health: from an ancient survival pathway to a modern therapeutic target",
  "title_text": "NRF2 as a guardian of health: from an ancient survival pathway to a modern therapeutic target",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:43Z",
  "url": "https://research.draconitic.com/paper/b3806mp07nd8z",
  "venue": "Redox Biology",
  "versions": []
}