Aging is associated with declines in tissue function that negatively impact health and independence. Pharmacological interventions to delay aging could prolong youthfulness and productivity in the aging population. However, identifying compounds that delay aging is expensive and time-consuming using the available mammalian models. This project aims to quickly identify lead compounds that can delay aging in the nematode, C. elegans. These lead compounds can be further studied for their effects in models that more closely approximate the human body. Current work is focused on two types of compounds that we have found to prolong lifespan, natural polyphenols in blueberries and the electron spin-trap nitroxide compound, tempol. Like many fruits and vegetables, blueberries contain high amounts of polyphenol compounds. In in vitro assays, these compounds possess high antioxidant activity. We have found that treatment with blueberry polyphenols can significantly prolong C. elegans average lifespan and delays the accumulation of aging-related damage. The bioactive compounds co-fractionate with a proanthocyanidin-enriched fraction, but not with other antioxidant polyphenols. Genetic analysis revealed that treatment with blueberry polyphenols did not lead to induction of stress resistance pathways. Our current model is that blueberry polyphenols protected cells from intrinsic stress that leads to cellular decline during aging. C. elegans lifespan was also significantly prolonged by treatment with the electron spin-trap nitroxide compound, tempol. At higher doses, tempol inhibited feeding and movement and caused larval lethality. Tempol did not appear to act as an antioxidant in vivo, as tempol treatment did not rescue lethality in mutants with increased oxidative stress. We hypothesize that tempol might interfere with normal mitochondrial function, since previous studies had shown that reductions of mitochondrial respiration can extend lifespan. We are currently investigating the effects of tempol on mitochondrial function.
