Study summary · research use only
An NAD(+)-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse study, the authors report that CD38, an NAD+-dependent metabolic enzyme, promotes hematopoietic stem cell (HSC) proliferation in young mice by inducing mitochondrial Ca2+ influx and mitochondrial metabolism, while aberrant CD38 upregulation during aging is described as contributing to HSC deterioration in aged mice through dysregulated NAD+ metabolism and impaired mitochondrial stress management. The mitochondrial calcium uniporter was also reported to support HSC proliferation in young mice but drive HSC decline in aged mice. Pharmacological inactivation of CD38 reversed HSC aging and related pathophysiological changes in aged mice. The authors describe an NAD+ metabolic checkpoint linking Ca2+ signaling to HSC aging.
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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