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The use of progeroid DNA repair-deficient mice for assessing anti-aging compounds, illustrating the benefits of nicotinamide riboside.
Birkisdóttir, María B; van Galen, Ivar; Brandt, Renata M C; Barnhoorn, Sander; van Vliet, Nicole; van Dijk, Claire; Nagarajah, Bhawani; Imholz, Sandra; van Oostrom, Conny T; Reiling, Erwin; Gyenis, Ákos; Mastroberardino, Pier G; Jaarsma, Dick; van Steeg, Harry; Hoeijmakers, Jan H J; Dollé, Martijn E T; Vermeij, Wilbert P.
Afiliación
  • Birkisdóttir MB; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
  • van Galen I; Oncode Institute, Utrecht, Netherlands.
  • Brandt RMC; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
  • Barnhoorn S; Oncode Institute, Utrecht, Netherlands.
  • van Vliet N; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • van Dijk C; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Nagarajah B; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Imholz S; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • van Oostrom CT; Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Reiling E; Centre for Health Protection, National Institute for Public Health and the Environment, (RIVM), Bilthoven, Netherlands.
  • Gyenis Á; Centre for Health Protection, National Institute for Public Health and the Environment, (RIVM), Bilthoven, Netherlands.
  • Mastroberardino PG; Centre for Health Protection, National Institute for Public Health and the Environment, (RIVM), Bilthoven, Netherlands.
  • Jaarsma D; Centre for Health Protection, National Institute for Public Health and the Environment, (RIVM), Bilthoven, Netherlands.
  • van Steeg H; , Faculty of Medicine, CECAD, Institute for Genome Stability in Aging and Disease, University of Cologne, Cologne, Germany.
  • Hoeijmakers JHJ; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Dollé MET; IFOM-The FIRC Institute of Molecular Oncology, Milan, Italy.
  • Vermeij WP; Department of Life, Health, and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Front Aging ; 3: 1005322, 2022.
Article en En | MEDLINE | ID: mdl-36313181
Despite efficient repair, DNA damage inevitably accumulates with time affecting proper cell function and viability, thereby driving systemic aging. Interventions that either prevent DNA damage or enhance DNA repair are thus likely to extend health- and lifespan across species. However, effective genome-protecting compounds are largely lacking. Here, we use Ercc1 Δ/- and Xpg -/- DNA repair-deficient mutants as two bona fide accelerated aging mouse models to test propitious anti-aging pharmaceutical interventions. Ercc1 Δ/- and Xpg -/- mice show shortened lifespan with accelerated aging across numerous organs and tissues. Previously, we demonstrated that a well-established anti-aging intervention, dietary restriction, reduced DNA damage, and dramatically improved healthspan, strongly extended lifespan, and delayed all aging pathology investigated. Here, we further utilize the short lifespan and early onset of signs of neurological degeneration in Ercc1 Δ/- and Xpg -/- mice to test compounds that influence nutrient sensing (metformin, acarbose, resveratrol), inflammation (aspirin, ibuprofen), mitochondrial processes (idebenone, sodium nitrate, dichloroacetate), glucose homeostasis (trehalose, GlcNAc) and nicotinamide adenine dinucleotide (NAD+) metabolism. While some of the compounds have shown anti-aging features in WT animals, most of them failed to significantly alter lifespan or features of neurodegeneration of our mice. The two NAD+ precursors; nicotinamide riboside (NR) and nicotinic acid (NA), did however induce benefits, consistent with the role of NAD+ in facilitating DNA damage repair. Together, our results illustrate the applicability of short-lived repair mutants for systematic screening of anti-aging interventions capable of reducing DNA damage accumulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Aging Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Aging Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza