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An NAD+-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging.
Song, Zehan; Park, Sang Hee; Mu, Wei-Chieh; Feng, Yufan; Wang, Chih-Ling; Wang, Yifei; Barthez, Marine; Maruichi, Ayane; Guo, Jiayue; Yang, Fanghan; Lin, Anita Wong; Heydari, Kartoosh; Chini, Claudia C S; Chini, Eduardo N; Jang, Cholsoon; Chen, Danica.
Afiliación
  • Song Z; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Park SH; Metabolic Biology Graduate Program, University of California, Berkeley, CA, USA.
  • Mu WC; Department of Biological Chemistry, University of California, Irvine, CA, USA.
  • Feng Y; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Wang CL; Endocrinology Graduate Program, University of California, Berkeley, CA, USA.
  • Wang Y; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Barthez M; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Maruichi A; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Guo J; Metabolic Biology Graduate Program, University of California, Berkeley, CA, USA.
  • Yang F; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Lin AW; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Heydari K; Endocrinology Graduate Program, University of California, Berkeley, CA, USA.
  • Chini CCS; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Chini EN; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
  • Jang C; Endocrinology Graduate Program, University of California, Berkeley, CA, USA.
  • Chen D; Cancer Research Laboratory, University of California, Berkeley, CA, USA.
Nat Aging ; 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-39044033
ABSTRACT
How hematopoietic stem cells (HSCs) maintain metabolic homeostasis to support tissue repair and regeneration throughout the lifespan is elusive. Here, we show that CD38, an NAD+-dependent metabolic enzyme, promotes HSC proliferation by inducing mitochondrial Ca2+ influx and mitochondrial metabolism in young mice. Conversely, aberrant CD38 upregulation during aging is a driver of HSC deterioration in aged mice due to dysregulated NAD+ metabolism and compromised mitochondrial stress management. The mitochondrial calcium uniporter, a mediator of mitochondrial Ca2+ influx, also supports HSC proliferation in young mice yet drives HSC decline in aged mice. Pharmacological inactivation of CD38 reverses HSC aging and the pathophysiological changes of the aging hematopoietic system in aged mice. Together, our study highlights an NAD+ metabolic checkpoint that balances mitochondrial activation to support HSC proliferation and mitochondrial stress management to enhance HSC self-renewal throughout the lifespan, and links aberrant Ca2+ signaling to HSC aging.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos