Transcriptomic study using RNA-seq in murine models of accelerated aging Zmpste24-/- treated with the supplements nicotinamide riboside (NR)
We evaluated the effects of NAD? precursor supplementation with nicotinamide riboside (NR) and niacin (NIA) in the accelerated aging Zmpste24-/- mouse model through systemic phenotyping and RNA-seq analysis. Both compounds extended lifespan; however, NR did so without restoring body weight, glycemia, or body temperature, indicating that these parameters are not required for lifespan extension. NR improved energy metabolism, oxygen consumption, and nighttime respiratory exchange ratio, and promoted marked rejuvenation in bone and cardiovascular tissues, whereas niacin showed more limited benefits and failed to rescue bone or hematological alterations. Transcriptomic analysis revealed that NR robustly restored aging-associated pathways, including fatty acid metabolism, mTOR and insulin signaling, hypoxia, p53, and bile acid metabolism, suggesting a broad metabolic reprogramming. Overall, while both NAD? precursors extend lifespan in Zmpste24-/- mice, NR provides a more comprehensive improvement in healthspan, highlighting the context-dependent effects of NAD?-boosting strategies.
We evaluated the effects of NAD? precursor supplementation with nicotinamide riboside (NR) and niacin (NIA) in the accelerated aging Zmpste24-/- mouse model through systemic phenotyping and RNA-seq analysis. Both compounds extended lifespan; however, NR did so without restoring body weight, glycemia, or body temperature, indicating that these parameters are not required for lifespan extension. NR improved energy metabolism, oxygen consumption, and nighttime respiratory exchange ratio, and promoted marked rejuvenation in bone and cardiovascular tissues, whereas niacin showed more limited benefits and failed to rescue bone or hematological alterations. Transcriptomic analysis revealed that NR robustly restored aging-associated pathways, including fatty acid metabolism, mTOR and insulin signaling, hypoxia, p53, and bile acid metabolism, suggesting a broad metabolic reprogramming. Overall, while both NAD? precursors extend lifespan in Zmpste24-/- mice, NR provides a more comprehensive improvement in healthspan, highlighting the context-dependent effects of NAD?-boosting strategies.