A microbiota and dietary metabolite integrates DNA repair and cell death to regulate embryo viability and aneuploidy during aging.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
24 02 2023
24 02 2023
Historique:
entrez:
24
2
2023
pubmed:
25
2
2023
medline:
3
3
2023
Statut:
ppublish
Résumé
During aging, environmental stressors and mutations along with reduced DNA repair cause germ cell aneuploidy and genome instability, which limits fertility and embryo development. Benevolent commensal microbiota and dietary plants secrete indoles, which improve healthspan and reproductive success, suggesting regulation of germ cell quality. We show that indoles prevent aneuploidy and promote DNA repair and embryo viability, which depends on age and genotoxic stress levels and affects embryo quality across generations. In young animals or with low doses of radiation, indoles promote DNA repair and embryo viability; however, in older animals or with high doses of radiation, indoles promote death of the embryo. These studies reveal a previously unknown quality control mechanism by which indole integrates DNA repair and cell death responses to preclude germ cell aneuploidy and ensure transgenerational genome integrity. Such regulation affects healthy aging, reproductive senescence, cancer, and the evolution of genetic diversity in invertebrates and vertebrates.
Identifiants
pubmed: 36827370
doi: 10.1126/sciadv.ade8653
pmc: PMC9956122
doi:
Substances chimiques
Indoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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