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Polyphenols and Metabolites Enhance Survival in Rodents and Nematodes—Impact of Mitochondria

Laboratory for Nutrition in Prevention and Therapy, Institute of Nutritional Sciences, Biomedical Research Center Seltersberg (BFS), Justus-Liebig-University of Giessen, Schubertstr. 81, 35392 Giessen, Germany
Institute of Nutritional and Food Sciences, Molecular Food Technology, University of Bonn, Endenicher Allee 19b, 53115 Bonn, Germany
Author to whom correspondence should be addressed.
Nutrients 2019, 11(8), 1886;
Received: 17 July 2019 / Revised: 1 August 2019 / Accepted: 7 August 2019 / Published: 13 August 2019
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(1) Background: Polyphenols (PP) play an important role in the prevention of non-communicable diseases and may contribute to healthy aging. To investigate the molecular and cellular aspects of PP metabolites on longevity with a focus on mitochondrial function, we applied a pre-fermented mixture of polyphenols (Rechtsregulat®, RR) to rodents and nematodes. (2) Methods: The lifespans of Navar Medical Research Institute (NMRI) mice and C. elegans were recorded. The heat-stress resistance (37 °C) of C. elegans N2 was measured using nucleic staining. Respiration and membrane potential (ΔΨm) were measured in isolated mitochondria. The energetic metabolites adenosine triphosphate (ATP), lactate, and pyruvate were determined in lysates. Expression levels of longevity related genes were determined using quantitative real time polymerase chain reaction (qRT-PCR). Phenolic compounds were identified using ultra high performance liquid chromatography-diode array detection-Iontrap-multiple stage mass spectrometry (UHPLC-DAD-Iontrap-MSn). (3) Results: Several phenolic metabolites including protocatechuic acid (PCA) were identified in RR. Feeding of mice with RR resulted in a significantly increased lifespan. Heat-stress resistance (RR *** p = 0.0006; PCA **** p < 0.0001), median lifespan (NMRI: RR ** p = 0.0035; C. elegans RR * p = 0.0279; PCA **** p < 0.0001), and activity of mitochondrial respiratory chain complexes (RR *** p = 0.0237 − 0.0052; PCA * p = 0.019 − 0.0208) of C. elegans were significantly increased after incubation with RR (10%) or PCA (780 µM). PCA significantly improved nematodes ΔΨm (* p = 0.02058) and ATP levels (* p = 0.029). RR significantly up-regulated lactate levels, indicating enhanced glycolysis. The expression levels of longevity related genes daf-16, sir-2.1, and skn-1 were significantly upregulated after PCA, and partially after RR administration. (4) Conclusion: Phenolic metabolites such as PCA have the potential to enhance health and lifespan and mitochondrial function, and thus may contribute to healthy aging. View Full-Text
Keywords: caenorhabditis elegans; mitochondria; longevity; polyphenol; respiration; protocatechuic acid caenorhabditis elegans; mitochondria; longevity; polyphenol; respiration; protocatechuic acid

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Dilberger, B.; Passon, M.; Asseburg, H.; Silaidos, C.V.; Schmitt, F.; Schmiedl, T.; Schieber, A.; Eckert, G.P. Polyphenols and Metabolites Enhance Survival in Rodents and Nematodes—Impact of Mitochondria. Nutrients 2019, 11, 1886.

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