CB-211

The effect of three phenols (ellagic, gentisic and gallic acids) from the axlewood treeAnogeissus leiocarpusonOnchocerca ochengiand drug-resistant strains ofCaenorhabditis elegans, a model organism for research on nematode parasites, is investigated. Worms were incubated in different concentrations of phenols and their survival was monitored after 48 h. Among the three acids, ellagic acid strongly affected the survival ofO. ochengimicrofilariae,O. ochengiadults, a wild-typeC. elegansand anthelmintic-resistant strains ofC. elegans, namely albendazole (CB3474), levamisole (CB211, ZZ16) and ivermectin (VC722, DA1316), with LC50values ranging from 0.03 mmto 0.96 mm. These results indicate that the binding of ellagic acid in the worm differs from that of resistant strains ofC. elegans. The efficacy of both gallic and gentisic acids was not significantly changed in resistant strains ofC. eleganstreated with levamisole (ZZ16, LC50= 9.98 mm, with gallic acid), albendazole (CB3474, LC50= 7.81 mm, with gentisic acid) and ivermectin (DA1316, LC50= 10.62 mm, with gentisic acid). The efficacy of these three pure compounds is in accordance with the use ofA. leiocarpusfrom its locality of origin. Thein vivotoxicity data reveal that the thresholds are up to 200 times higher than the determined LC50values. Thus, ellagic acid could be a potential option for the treatment of nematode infections, even in cases of drug resistance towards established anthelmintic drugs.

Background: Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased cellular damage and death. These conditions play an essential role in aging and significantly contribute to the development of age-related complications. Humanin is a mitochondrial-derived peptide (MDP), encoded by mitochondrial DNA, playing a cytoprotective role to preserve mitochondrial function and cell viability under stressful and senescence conditions. For these reasons, humanin can be exploited in strategies aiming to counteract several processes involved in aging, including cardiovascular disease, neurodegeneration, and cancer. Relevance of these conditions to aging and disease: Senescence appears to be involved in the decay in organ and tissue function, it has also been related to the development of age-related diseases, such as cardiovascular conditions, cancer, and diabetes. In particular, senescent cells produce inflammatory cytokines and other pro-inflammatory molecules that can participate to the development of such diseases. Humanin, on the other hand, seems to contrast the development of such conditions, and it is also known to play a role in these diseases by promoting the death of damaged or malfunctioning cells and contributing to the inflammation often associated with them. Both senescence and humanin-related mechanisms are complex processes that have not been fully clarified yet. Further research is needed to thoroughly understand the role of such processes in aging and disease and identify potential interventions to target them in order to prevent or treat age-related conditions. Objectives: This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, humanin, aging, and disease.