Lifespan extension by cranberry supplementation partially requires SOD2 and is life stage independent

Abstract

Many nutraceuticals and pharmaceuticals have been shown to promote healthspan and lifespan. However, the mechanisms underlying the beneficial effects of prolongevity interventions and the time points at which interventions should be implemented to achieve beneficial effects are not well characterized. We have previously shown that a cranberry-containing nutraceutical can promote lifespan in worms and flies and delay age-related functional decline of pancreatic cells in rats. Here we investigated the mechanism underlying lifespan extension induced by cranberry and the effects of short-term or life stage-specific interventions with cranberry on lifespan in Drosophila. We found that lifespan extension induced by cranberry was associated with reduced phosphorylation of ERK, a component of oxidative stress response MAPK signaling, and slightly increased phosphorylation of AKT, a component of insulin-like signaling. Lifespan extension was also associated with a reduced level of 4-Hydroxynonenal protein adducts, a biomarker of lipid oxidation. Moreover, lifespan extension induced by cranberry was partially suppressed by knockdown of SOD2, a major mitochondrial superoxide scavenger. Furthermore, cranberry supplementation was administered in three life stages of adult flies, health span (3–30 days), transition span (31–60 days) and senescence span (61 days to the end when all flies died). Cranberry supplementation during any of these life stages extended the remaining lifespan relative to the non-supplemented and life stage-matched controls. These findings suggest that cranberry supplementation is sufficient to promote longevity when implemented during any life stage, likely through reducing oxidative damage.

Dietary ursolic acid improves health span and life span in male Drosophila melanogaster

“…Some secondary plant compounds and plant extracts, for example, curcumin , anthocyanins , and cranberry extract , have been shown to reduce oxidative stress in Drosophila presumably contributing to life span prolongation. There is evidence that srl ‐overexpressing flies show higher survival rates than wild‐type flies following oxidative stress exposure .…”

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

“…In addition to these major pathways and genes, ROS is also involved in regulating longevity [16]. High ROS activity has been shown to be a major lifespan limiting factor in humans, C. elegans, and Drosophila [7,[17][18][19]. Finally, in addition to the factors discussed above, mitochondria regulate different signaling and metabolic pathways, including ROS production and therefore plays a vital role in aging progression [20].…”

Superoxide Dismutase (SOD) Genes and Aging in Drosophila

“…Studies in yeast demonstrate the role of Cu/ZnSOD in repressing metabolism in response to glucose (Reddi and Culotta 2013). Similarly, Drosophila MnSOD gene activity was found to be required for the longevity-promoting effects of cranberry extract (Sun et al 2014), supporting a diet-dependent interaction between MnSOD and life span (Fig. 3.1).…”