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.
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.
Access the full paper
Related research
Nature Communications · 2016
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans
NR is orally bioavailable in humans and raises blood NAD+ without flushing.
Cell Reports · 2019
Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome
NR raises tissue NAD+ in aged muscle and shifts mitochondrial transcription.
Scientific Reports · 2019
Safety and metabolism of long-term administration of NIAGEN (Nicotinamide Riboside Chloride) in healthy middle-aged and older adults
NR is well tolerated at doses up to 1 g/day over 8 weeks in healthy adults.