Nicotinamide riboside functions during development while beta-hydroxybutyrate functions during adulthood to extend C....

Area of Science:

• Gerontology and aging research
• Molecular biology and cellular stress responses
• Nutritional biochemistry and metabolism

Background:

• Nicotinamide riboside (NR), a vitamin B3 derivative and NAD+ precursor, activates the mitochondrial unfolded protein response (UPRmt).
• Beta-hydroxybutyrate (BHB), a ketone body and HDAC inhibitor, also extends lifespan.
• Both NR and BHB have demonstrated lifespan-extending properties in C. elegans models.

Purpose of the Study:

• To investigate the distinct temporal effects of NR and BHB on C. elegans lifespan.
• To determine the impact of combining NR and BHB treatments on longevity.
• To explore the underlying mechanisms, including hormesis and pathway convergence, of NR and BHB's lifespan effects.

Main Methods:

• Supplementation of C. elegans with nicotinamide riboside (NR) during larval development.
• Supplementation of C. elegans with beta-hydroxybutyrate (BHB) during adulthood.
• Comparative analysis of lifespan extension in response to individual and combined NR and BHB treatments.

Main Results:

• NR significantly extended C. elegans lifespan when administered during larval development.
• BHB significantly extended C. elegans lifespan when administered during adulthood.
• The combination of NR during development and BHB during adulthood unexpectedly decreased lifespan.

Conclusions:

• NR and BHB exert their lifespan-extending effects through distinct temporal mechanisms.
• The antagonistic effect of combined NR and BHB suggests the involvement of hormesis and parallel longevity pathways.
• These pathways likely converge on a common downstream target, mediating the observed lifespan alterations.