NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice
Zhang H, Ryu D, Wu Y, et al.
Key finding
Oral NR at 400 mg/kg/day extends aged-mouse lifespan and restores stem cell function through SIRT1 and mitochondrial UPR. Source: Zhang H, Ryu D, Wu Y, et al. Science, 2016.
Summary
Mouse study from the Auwerx laboratory showing that oral NR supplementation extends lifespan and rescues adult stem cell function in aged animals. 24-month-old C57BL/6J mice given 400 mg/kg/day NR in drinking water for six weeks exhibited increased muscle stem cell (satellite cell) number and myogenic capacity, improved neural stem cell function, and restored intestinal stem cell compartment integrity. NR-treated aged mice showed improved mitochondrial function (membrane potential, respiration, mtDNA copy number), reduced senescence markers, and extended median lifespan by approximately 5%. Mechanistically, the improvements depended on SIRT1-mediated mitochondrial UPR activation and were blunted in SIRT1 knockouts. The study is one of the few published mouse lifespan experiments for an oral NAD+ precursor and paired the longevity outcome with mechanistic stem-cell biology — strengthening the translational case for NAD+-boosting interventions as systemic gerotherapeutics. Dose translates to approximately 1.9 g/day human-equivalent via standard allometric scaling.
For background on the compound studied here, see our NR precursor reference.
Frequently asked questions
- What did Zhang et al. (2016) find about NR?
- Oral NR at 400 mg/kg/day extends aged-mouse lifespan and restores stem cell function through SIRT1 and mitochondrial UPR. Source: Zhang H, Ryu D, Wu Y, et al. "NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice." Science, 2016.
- What kind of study is Zhang 2016?
- It is a mechanism study on NR published in Science in 2016. Mouse study from the Auwerx laboratory showing that oral NR supplementation extends lifespan and rescues adult stem cell function in aged animals. 24-month-old C57BL/6J mice given 400 mg/kg/day NR in drinking water for six weeks exhibited increased muscle stem cell (satellite cell) number and myogenic capacity, improved neural stem cell function, and restored intestinal stem cell compartment integrity. NR-treated aged mice showed improved mitochondrial function (membrane potential, respiration, mtDNA copy number), reduced senescence markers, and extended median lifespan by approximately 5%. Mechanistically, the improvements depended on SIRT1-mediated mitochondrial UPR activation and were blunted in SIRT1 knockouts. The study is one of the few published mouse lifespan experiments for an oral NAD+ precursor and paired the longevity outcome with mechanistic stem-cell biology — strengthening the translational case for NAD+-boosting interventions as systemic gerotherapeutics. Dose translates to approximately 1.9 g/day human-equivalent via standard allometric scaling.
- Where can I read the full Zhang 2016 paper?
- The primary source is available on PubMed (PMID 27127236) and via DOI 10.1126/science.aaf2693.
Access the full paper
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