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Aging in orbit: The twelve hallmarks as a bidirectional bridge between spaceflight-induced senescence and terrestrial geroscience.

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Title: Aging in orbit: The twelve hallmarks as a bidirectional bridge between spaceflight-induced senescence and terrestrial geroscience.
Authors: Minoretti P; Department of Social Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain; Studio Minoretti, Oggiono, Lecco, Italy., Lista S; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain., López-Ortiz S; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain., Merino-País M; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain., Santos-Lozano A; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid, Spain., Lucia A; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid, Spain; Department of Sport Sciences, Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, Madrid, Spain., Emanuele E; 2E Science, Robbio, Pavia, Italy. Electronic address: enzo.emanuele@2escience.com.
Source: Ageing research reviews [Ageing Res Rev] 2026 Jul; Vol. 119, pp. 103191. Date of Electronic Publication: 2026 May 28.
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Elsevier Science Country of Publication: England NLM ID: 101128963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9649 (Electronic) Linking ISSN: 15681637 NLM ISO Abbreviation: Ageing Res Rev Subsets: MEDLINE
Imprint Name(s): Original Publication: Oxford, UK : Elsevier Science, c2002-
MeSH Terms: Aging*/physiology , Aging*/genetics , Weightlessness*/adverse effects , Space Flight* , Geroscience*, Cosmic Radiation/adverse effects ; Cellular Senescence/physiology ; Humans ; Animals
Abstract: Human spaceflight exposes crew members to a combination of environmental stressors - including microgravity, galactic cosmic radiation, circadian disruption, and prolonged confinement - that together induce multisystem physiological changes resembling terrestrial aging. In this narrative review, we examine how short- and medium-term spaceflight affects all twelve recognized hallmarks of aging. Integrated multi-omics analyses in astronauts and rodent models identified mitochondrial dysfunction as a central node of spaceflight biology, with oxidative damage propagating genomic instability, cellular senescence, and chronic inflammation. At the chromosomal level, telomere dynamics were characterized by a paradoxical elongation-shortening cycle that may compress years of terrestrial attrition into months. In parallel, epigenetic clock analyses showed a ∼1.9-year biological age acceleration in astronauts after a 9-day orbital mission, with hierarchical post-flight recovery (reversible transcriptomic and epigenomic shifts versus persistent chromosomal inversions and clonal hematopoiesis mutations). This partial reversibility distinguishes the spaceflight paradigm from the largely unidirectional trajectory of chronological aging. We conclude that the relationship between spaceflight biology and terrestrial geroscience is bidirectional. Aging research on Earth provides the interpretive framework that renders astronaut molecular data biologically meaningful, and spaceflight offers geroscience a compressed, partially reversible aging-like phenotype in healthy young subjects that has no direct terrestrial counterpart. The observation that space radiation induces qualitatively distinct senescent phenotypes amenable to senolytic clearance supports a translational framework in which geroprotective strategies may simultaneously serve astronaut health and promote healthy longevity in the broader aging population.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Given his role as an Associate Editor of Ageing Research Reviews, Alejandro Lucia had no involvement in the peer review of this article and had no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to another journal editor. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Biological age acceleration; Epigenetic clock; Galactic cosmic radiation; Geroscience; Hallmarks of aging; Spaceflight
Entry Date(s): Date Created: 20260529 Date Completed: 20260605 Latest Revision: 20260605
Update Code: 20260606
DOI: 10.1016/j.arr.2026.103191
PMID: 42214505
Database: MEDLINE
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  Data: Aging in orbit: The twelve hallmarks as a bidirectional bridge between spaceflight-induced senescence and terrestrial geroscience.
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  Data: <searchLink fieldCode="AU" term="%22Minoretti+P%22">Minoretti P</searchLink>; Department of Social Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain; Studio Minoretti, Oggiono, Lecco, Italy.<br /><searchLink fieldCode="AU" term="%22Lista+S%22">Lista S</searchLink>; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain.<br /><searchLink fieldCode="AU" term="%22López-Ortiz+S%22">López-Ortiz S</searchLink>; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain.<br /><searchLink fieldCode="AU" term="%22Merino-País+M%22">Merino-País M</searchLink>; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain.<br /><searchLink fieldCode="AU" term="%22Santos-Lozano+A%22">Santos-Lozano A</searchLink>; i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid, Spain.<br /><searchLink fieldCode="AU" term="%22Lucia+A%22">Lucia A</searchLink>; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid, Spain; Department of Sport Sciences, Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, Madrid, Spain.<br /><searchLink fieldCode="AU" term="%22Emanuele+E%22">Emanuele E</searchLink>; 2E Science, Robbio, Pavia, Italy. Electronic address: enzo.emanuele@2escience.com.
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  Data: Human spaceflight exposes crew members to a combination of environmental stressors - including microgravity, galactic cosmic radiation, circadian disruption, and prolonged confinement - that together induce multisystem physiological changes resembling terrestrial aging. In this narrative review, we examine how short- and medium-term spaceflight affects all twelve recognized hallmarks of aging. Integrated multi-omics analyses in astronauts and rodent models identified mitochondrial dysfunction as a central node of spaceflight biology, with oxidative damage propagating genomic instability, cellular senescence, and chronic inflammation. At the chromosomal level, telomere dynamics were characterized by a paradoxical elongation-shortening cycle that may compress years of terrestrial attrition into months. In parallel, epigenetic clock analyses showed a ∼1.9-year biological age acceleration in astronauts after a 9-day orbital mission, with hierarchical post-flight recovery (reversible transcriptomic and epigenomic shifts versus persistent chromosomal inversions and clonal hematopoiesis mutations). This partial reversibility distinguishes the spaceflight paradigm from the largely unidirectional trajectory of chronological aging. We conclude that the relationship between spaceflight biology and terrestrial geroscience is bidirectional. Aging research on Earth provides the interpretive framework that renders astronaut molecular data biologically meaningful, and spaceflight offers geroscience a compressed, partially reversible aging-like phenotype in healthy young subjects that has no direct terrestrial counterpart. The observation that space radiation induces qualitatively distinct senescent phenotypes amenable to senolytic clearance supports a translational framework in which geroprotective strategies may simultaneously serve astronaut health and promote healthy longevity in the broader aging population.<br /> (Copyright © 2026 Elsevier B.V. All rights reserved.)
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  Data: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Given his role as an Associate Editor of Ageing Research Reviews, Alejandro Lucia had no involvement in the peer review of this article and had no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to another journal editor. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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