Two Natural Product Compositions Improve Lifespan and Healthspan in Caenorhabditis Elegans by Targeting the Hallmarks of Aging

Aging has been increasingly recognized as a global health burden. Current aging research suggests that preventative strategies may increase both lifespan and healthspan. Many natural compounds or natural products have demonstrated promising antiaging benefits and gained popularity in aging research. The present study evaluated two compositions comprised of nicotinamide mononucleotide, quercetin, alpha ketoglutarate, white button mushroom extract (standardized to spermidine), Transfer Factor (TF) (extracts from cow colostrum and chicken egg yolk) with or without milk thistle fruit extract (standardized to silybin) and apigenin for their antiaging effect in Caenorhabditis elegans (i.e., C. elegans). The active ingredients included in the two compositions were screened for their senolytic effects on cell viability of irradiated human umbilical vein endothelial cells. To further explore their potential molecular mechanisms of action, the two compositions were also tested for their binding activity to human sirtuin enzymes and TF on natural killer cell activities in human peripheral blood mononuclear cells from both young and old donors. Both compositions significantly increased the lifespan and healthspan of C. elegans. Both compositions demonstrated significant dose-dependent inhibitory effect on several sirtuins. When treated with TF, both younger and older human peripheral blood mononuclear cells bolstered natural killer cell activity. The present study suggested that these two compositions significantly improved both lifespan and healthspan of C. elegans likely by modulating sirtuin activity and rejuvenating senescent immune cells. Keywords Lifespan; Healthspan; Transfer factor; Nicotinamide mononucleotide; Spermidine