Abstract

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.

Highlights

  • Aging has a significant influence on economy, health, and demography with healthy aging being a global challenge [1]

  • We demonstrated that Tart cherry (TC) extract (TCE) extends lifespan and healthspan of C. elegans by influencing the major DAF-16/forkhead box O1 (FOXO) lifespan regulating pathway

  • We found that feeding C. elegans lower concentrations of TCE (3, 6, and 12 μg/mL) resulted in significant extension of mean lifespan (MLS) by 12.09% (p > 0.05), 26.44% (p < 0.05), and 25.69% (p < 0.05), respectively

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Summary

Introduction

Aging has a significant influence on economy, health, and demography with healthy aging being a global challenge [1]. 9% of the population was old (over age 65) in 2019, which is expected to increase to 16% by 2050 [3]. Genetic and lifestyle factors contribute to aging and healthy lifespan. Various factors contribute to aging such as defects in development and genetics, environmental factors, diseases, and reactive oxygen species (ROS), which cause harmful changes in cells and tissues [5]. Excessive ROS production causes oxidative stress, which is a predominant factor in the pathophysiology of various diseases and aging in human and other models [6] such as Caenorhabditis elegans (C. elegans) [7] and Drosophila [8]. Human studies are scarce [12], and the safety and effectiveness of calorie restriction for lifespan

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