Introduction: Aging and health span 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 C. 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 dietary bioactive compounds such as tart cherry (TC) with antioxidant properties may exert dual benefits in mitochondrial function, oxidative stress resulting in beneficial effects on aging. We hypothesize that TC, rich in antioxidant anthocyanins, confers health span benefits in C. elegans through enhanced mitochondrial function and anti-oxidant property, mainly via the DAF-16 pathway. Methods: Lifespan assays were conducted in micropillar devices using age-synchronized Bristol N2 and
daf-16 (GR1307) C. elegans. Worms were fed concentrated E. coli OP50 (100mg/ml) suspended in nematode growth media supplemented with TC extract at final doses of 3, 6, and 12 g/ml of anthocyanins. Gene expression analysis was performed at
day10 to test DAF-16 pathway (
daf-16,
aak-2, akt, and
daf-2), and antioxidant genes (
sod-2/3). Data were normalized to the 18s housekeeping gene. Seahorse analyzer was used to determine mitochondrial maximal or spare respiration capacity. Results: TC supplementation at 6ug or 12ug/ml, significantly increased (p<0.05) the mean lifespan of N2 worms (19.25 plus or minus 0.24 and 19.45 plus or minus 0.24 days) respectively, when compared to untreated control worms (12.75 plus or minus 0.23 days). Consistent with these findings, TC upregulated (p<0.05) expression of longevity-related genes such as
daf-16, and
aak-2 (but not
daf-2 or
akt-2 genes). Interestingly, these effects of TC did not extend lifespan of
daf-16 (GR1307) worms. Moreover, TC upregulated (p<0.05) antioxidant gene expression (
sod-2) in N2 worms. In line with these results, TC prevented the age-related decline of mitochondrial capacity which was measured by increase in spare respiration capacity (p<0.05) in N2 worms. Conclusion: TC increases the lifespan of C. elegans, in a DAF-16-dependent manner. This may be due to enhanced both antioxidant and spare respiratory, allowing cells to function better under stressful conditions. Further studies are warranted to understand mechanisms linking oxidative stress, respiration, and longevity and their regulation by dietary antioxidants