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We examined the effects of the extracts from two traditional Chinese medicine plants, Cuscuta chinensis and Eucommia ulmoides, on the healthspan of the model organism Caenorhabditis elegans. C. chinensis increased the short-term memory and the mechanosensory response of aged C. elegans. Furthermore, both extracts improved the resistance towards oxidative stress, and decreased the intracellular level of reactive oxygen species. Chemical analyses of the extracts revealed the presence of several bioactive compounds such as chlorogenic acid, cinnamic acid, and quercetin. A fraction from the C. chinensis extract enriched in zingibroside R1 improved the lifespan, the survival after heat stress, and the locomotion in a manner similar to the full C. chinensis extract. Thus, zingibroside R1 could be (partly) responsible for the observed health benefits of C. chinensis. Furthermore, a hydroxygallic acid derivative and the sterol lipid 4-alpha-formyl-stigmasta-7,24(241)-dien-3-beta-ol are abundantly present in the C. chinensis extract and its most bioactive fraction, but hardly in E. ulmoides, making them good candidates to explain the overall healthspan benefits of C. chinensis compared to the specific positive effects on stress resistance by E. ulmoides. Our findings highlight the overall anti-aging effects of C. chinensis in C. elegans and provide first hints about the components responsible for these effects., European Union’s Horizon 2020 research and innovation program, Humboldt-University of Berlin, Germany, German Research Foundation (DFG), Open Access Publication Fund of Humboldt-Universität zu Berlin, Peer Reviewed

The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans, we compile a list of features of health and of the genes associated with them. These genes may or may not be associated with survival/lifespan. In turn, survival/lifespan genes that are not known to be directly associated with health are not considered. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans and for C. elegans. Overlaying healthspan-related gene expression data onto the healthspan pathway maps, we observe the downregulation of (pro-inflammatory) Notch signaling in humans and of proliferation in C. elegans. We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, should be seen as a pilot investigation of the molecular underpinnings of health in two different species., Funding Agencies:Fonds de la Recherche en Sante du QuebecEstonian Research Agency grant IUT34-4FWO 11A5420NBME NC TKP2020 grant of NKFIH Hungary BME-Biotechnology FIKP grant of EMMI (BME FIKP-BIO) Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA) K119866

Recent research has highlighted that the polyphenols Quercetin and Tannic acid are capable of extending the lifespan of Caenorhabditis elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to three concentrations of Quercetin or Tannic acid, respectively. By means of an intricate meta-analysis it was possible to compare the transcriptomes of polyphenol exposure to recently published datasets derived from (i) longevity mutants or (ii) infection. This detailed comparative in silico analysis facilitated the identification of compound specific and overlapping transcriptional profiles and allowed the prediction of putative mechanistic models of Quercetin and Tannic acid mediated longevity. Lifespan extension due to Quercetin was predominantly driven by the metabolome, TGF-beta signaling, Insulin-like signaling, and the p38 MAPK pathway and Tannic acid’s impact involved, in part, the amino acid metabolism and was modulated by the TGF-beta and the p38 MAPK pathways. DAF-12, which integrates TGF-beta and Insulin-like downstream signaling, and genetic players of the p38 MAPK pathway therefore seem to be crucial regulators for both polyphenols. Taken together, this study underlines how meta-analyses can provide an insight of molecular events that go beyond the traditional categorization into gene ontology-terms and Kyoto encyclopedia of genes and genomes-pathways. It also supports the call to expand the generation of comparative and integrative databases, an effort that is currently still in its infancy., Peer Reviewed

Tannine sind pflanzliche, polyphenolische Sekundärmetabolite mit Protein-präzipitierenden und –bindenden Kapazitäten, welche offenbar für die antinutritiven und gesundheitsschädlichen Wirkungen der Tannine verantwortlich sind. Jedoch dominieren in der Literatur die gesundheitsfördernden Beschreibungen, für die meist die antioxidative Kapazität verantwortlich gemacht wurde. Der etablierte Modelorganismus Caenorhabditis elegans wurde zur Analyse dieses Kontrastes ausgewählt. Zunächst wurden Lebensdauer und Stressresistenz der mit Tanninsäure und den Tanninbausteinen Gallussäure, Ellagsäure und Catechin behandelten Nematoden ermittelt. Das vermutete Vorliegen eines „Calorie Restriction“ (CR)-Effektes als auch einer hormetischen Dosis-Wirkungs-Beziehung wurde überprüft. Weiterhin wurden antimikrobielle und antioxidative Eigenschaften als potentielle Ursachen der Langlebigkeit untersucht und die Auswirkungen auf die Fitness und Genexpression analysiert. Die Einbeziehung verschiedener Alterungs-Theorien rundete die Analyse der Tanninwirkung ab. Alle Tannin-Substanzen konnten eine Lebensverlängerung erwirken, doch erstaunlicherweise erwiesen sich Langlebigkeit und Stressresistenz als individuelle, nicht zwangsläufig gekoppelte Parameter. Hormesis, CR-nachahmende Eigenschaften, antimikrobielle Kapazitäten als auch verschiedene stressrelevante Gene sind teilweise für die Lebensverlängerung verantwortlich. Die antioxidative Kapazität scheint jedoch irrelevant zu sein. Die differentielle Expression mehrerer hundert Gene durch Tanninsäure unterstreicht zudem die Komplexität der Wirkweise. Hinweise zur Bestätigung der „Disposable Soma Theory“, der „Mitohormesis“-Theorie und der „Green Theory of Ageing“ konnten zum Teil gefunden werden. Diese Arbeit zeigt die individuelle und kontrastreiche Wirksamkeit der Tannine auf. Sie unterstreicht, dass Tannine molekulare Regulatoren sind, welche nicht nur auf ihre antioxidative und antinutritive Kapazität reduziert werden sollten., The polyphenolic tannins are plant-produced secondary metabolites with protein precipitating and binding capacities. This characteristic is seemingly responsible for antinutritional and harmful effects. However, health benefits have also been extensively described in the literature. Indeed, antioxidant properties are believed to be the reason for these beneficial effects. The established model organism Caenorhabditis elegans was chosen to examine this apparent contradiction. The nematodes were exposed to tannic acid and to the tannin building blocks gallic acid, ellagic acid, and catechin and the lifespan and stress resistance were determined. The presence of a calorie restriction (CR) effect and a hormetic dose-response-relationship was verified. Furthermore, antimicrobial and antioxidative capacities were assessed as possible causes of longevity and the impact on fitness parameters and gene expressions was analysed. The consideration of different ageing theories completed the analysis of the tannin action. All tannin-substances were able to prolong the lifespan but against all expectations, longevity and stress resistance were shown to be independent entities, which are not necessarily linked. Hormesis, CR-mimetic properties, antimicrobial capacities as well as several stress relevant genes are partly responsible for the life-extension. The antioxidant capacities, however, appeared to be irrelevant. The regulation of several hundred gene expressions by tannic acid underlined the complexity of the mode of action. Furthermore, the results partly confirm the “Disposable Soma Theory”, the “Mitohormesis Theory” and the “Green Theory of Ageing”. This work dissects the contrasting efficiency of the tannin family and underlines in particular, that tannins are molecular regulators, which should not be reduced to their antioxidative and antinutritional capacities