Tart Cherry Increases Lifespan in Caenorhabditis elegans by Altering Metabolic Signaling Pathways

Aging and healthspan are determined by both environmental and genetic factors. The insulin/insulin-like growth factor-1(IGF-1) pathway is a key mediator of aging in Caenorhabditis elegans and mammals. Specifically, DAF-2 signaling, an ortholog of human IGF, controls DAF-16/FOXO transcription factor, a master regulator of metabolism and longevity. Moreover, mitochondrial dysfunction and oxidative stress are both linked to aging. We propose that daily supplementation of tart cherry extract (TCE), rich in anthocyanins with antioxidant properties may exert dual benefits for mitochondrial function and oxidative stress, resulting in beneficial effects on aging in C. elegans. We found that TCE supplementation at 6 μg or 12 μg/mL, increased (p < 0.05) the mean lifespan of wild type N2 worms, respectively, when compared to untreated control worms. Consistent with these findings, TCE upregulated (p < 0.05) expression of longevity-related genes such as daf-16 and aak-2 (but not daf-2 or akt-1 genes) and genes related to oxidative stress such as sod-2. Further, we showed that TCE supplementation increased spare respiration in N2 worms. However, TCE did not change the mean lifespan of daf-16 and aak-2 mutant worms. In conclusion, our findings indicate that TCE confers healthspan benefits in C. elegans through enhanced mitochondrial function and reduced oxidative stress, mainly via the DAF-16 pathway.