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

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.

The Review of Anti-aging Mechanism of Polyphenols on Caenorhabditis elegans

“…Many studies have focused on the anti-oxidant capacity of different plant extracts rich with anthocyanins. The vast majority of plant extracts rich in anthocyanins, such as extracts of purple wheat (Chen et al, 2013 ), acai berry (Peixoto et al, 2016 ), mulberry (Yan et al, 2017 ), purple pitanga fruit (Tambara et al, 2018 ), tart cherry (Jayarathne et al, 2020 ), and bilberry (Gonzalez-Paramas et al, 2020 ), which can play their beneficial role by increasing nuclear translocation of DAF-16 and promoting the expression of anti-oxidant genes, such as sod-3 , and the heat shock gene, hsp-16.2 , in its downstream. Heat shock proteins (HSPs) are molecular chaperones and play important roles in the protection of molecular damage under environmental stress and have the ability to maintain proteostasis and prolong the longevity of organisms (Swindell, 2009 ).…”

“…DAF-16 is a key protein for the anti-aging effects. Mechanistically, recent studies have found that anthocyanins could regulate the AAK-2/AMPK signaling pathway to perform its biological function (Jayarathne et al, 2020 ). aak-2 is the encoding gene of AMPK in nematodes.…”

Natural Products in the Prevention of Metabolic Diseases: Lessons Learned from the 20th KAST Frontier Scientists Workshop

“…Changes during aging are often linked to mitochondrial dysfunction. For the first time, we demonstrated that worms fed TC extracts exhibited increased mitochondrial spare respiration, and expression of uncoupling protein 4 and antioxidant markers such as superoxide dismutase (SOD)-3 [59]. Additional research is warranted both in mouse models and clinical studies to better understand the detailed molecular mechanisms of TC in aging and determine the most effective dose for human consumption.…”

“…Dietary antioxidants have potential roles in lowering oxidative stress associated with aging and chronic conditions [58]. We have recently reported that TC extract rich in anthocyanins with antioxidant activity increased lifespan in C. elegans mainly via insulin/insulin-like growth factor-1 signaling (IIS) by regulating DAF-2 and DAF-16 expression, major components of the IIS pathway [59]. Changes during aging are often linked to mitochondrial dysfunction.…”

Review of Biological Effects of Acute and Chronic Radiation Exposure on Caenorhabditis elegans

“…E. coli DA837 and Bacillus simplex are intermediate food sources [39]. Additionally, several investigations reported that food sources that contain phytochemicals such as blueberry polyphenols [40], epigallocatechin gallate from tea [41], plant adaptogens [42], and tart cherry [43], among others, increase the life span of C. elegans.…”