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Causality-enriched epigenetic age uncouples damage and adaptation.
Ying, Kejun; Liu, Hanna; Tarkhov, Andrei E; Sadler, Marie C; Lu, Ake T; Moqri, Mahdi; Horvath, Steve; Kutalik, Zoltán; Shen, Xia; Gladyshev, Vadim N.
Afiliación
  • Ying K; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Liu H; T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Tarkhov AE; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Sadler MC; Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
  • Lu AT; Department of Pharmacy, Massachusetts General Hospital, Boston, MA, USA.
  • Moqri M; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Horvath S; University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
  • Kutalik Z; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Shen X; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Gladyshev VN; Altos Labs, San Diego, CA, USA.
Nat Aging ; 4(2): 231-246, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38243142
ABSTRACT
Machine learning models based on DNA methylation data can predict biological age but often lack causal insights. By harnessing large-scale genetic data through epigenome-wide Mendelian randomization, we identified CpG sites potentially causal for aging-related traits. Neither the existing epigenetic clocks nor age-related differential DNA methylation are enriched in these sites. These CpGs include sites that contribute to aging and protect against it, yet their combined contribution negatively affects age-related traits. We established a new framework to introduce causal information into epigenetic clocks, resulting in DamAge and AdaptAge-clocks that track detrimental and adaptive methylation changes, respectively. DamAge correlates with adverse outcomes, including mortality, while AdaptAge is associated with beneficial adaptations. These causality-enriched clocks exhibit sensitivity to short-term interventions. Our findings provide a detailed landscape of CpG sites with putative causal links to lifespan and healthspan, facilitating the development of aging biomarkers, assessing interventions, and studying reversibility of age-associated changes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Epigénesis Genética Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Epigénesis Genética Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos