NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice

Area of Science:

• Cellular senescence
• Mitochondrial function
• Stem cell biology

Background:

• Adult stem cells (SCs) are crucial for tissue repair but decline with age.
• Cellular aging (senescence) impairs SC function.
• Oxidative nicotinamide adenine dinucleotide (NAD(+)) levels impact mitochondrial activity and SC health.

Purpose of the Study:

• To investigate the role of NAD(+) in modulating muscle stem cell (MuSC) senescence.
• To determine if NAD(+) precursors can rejuvenate aged MuSCs.
• To explore the potential of NAD(+) conservation strategies for improving lifespan.

Main Methods:

• Administered nicotinamide riboside (NR), an NAD(+) precursor, to aged mice.
• Utilized the mdx mouse model for muscular dystrophy.
• Assessed MuSC function, senescence markers, and mitochondrial activity.
• Evaluated effects on neural SCs, melanocyte SCs, and overall mouse lifespan.

Main Results:

• NR treatment induced the mitochondrial unfolded protein response and prohibitin synthesis.
• NR rejuvenated MuSCs in aged mice and prevented senescence in mdx mice.
• NR delayed senescence in neural and melanocyte SCs.
• NR administration extended mouse lifespan.

Conclusions:

• NAD(+) levels and mitochondrial activity are key regulators of SC senescence.
• NR treatment effectively rejuvenates aged and dysfunctional SCs.
• Strategies to conserve cellular NAD(+) hold promise for combating aging and extending lifespan.