Coniferaldehyde activates autophagy and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans via par-4/aak-2/skn-1 pathway

Dec 14, 2024Biogerontology

Coniferaldehyde boosts cell cleaning, stress resistance, and lifespan in worms through the par-4/aak-2/skn-1 pathway

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Abstract

50 µM coniferaldehyde (CFA) significantly activates autophagy and reduces oxidative stress in Caenorhabditis elegans.

CFA treatment enhances the activity of antioxidant enzymes and increases resistance to oxidative stress.
CFA effectively decreases levels of reactive oxygen species (ROS) and promotes the expression of antioxidant genes.
CFA promotes SKN-1 protein localization to the nucleus, which influences the expression of the gst-4 gene.
The activation of the PAR-4/LKB-1-AAK-2/AMPK-SKN-1/NRF-2 pathway is associated with reduced oxidative stress and enhanced lifespan.
Key genes, bec-1 and lgg-1, play important roles in autophagy-mediated lifespan extension.

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Aging represents the gradual accumulation of alterations within an organism over time. The physical and chemical characteristics of our cells gradually change as we age, making it more difficult for our tissues and organs to self-regulate, regenerate, and maintain their structural and functional integrity. AMP- activated protein kinase (AMPK), a well-known sensor of cellular energy status acts as a central regulator of an integrated signalling network that control homeostasis, metabolism, stress resistance, cell survival and autophagy. Coniferaldehyde (CFA), a phenolic compound found in many edible plants, has multiple biological and pharmacological functions. Our findings demonstrated that 50 µM CFA could significantly activate autophagy and reduce oxidative stress, which enhanced the activity of antioxidant enzymes and increased resistance under oxidative stress. CFA treatment could efficiently decrease reactive oxygen species (ROS) levels and positively enhance the expression of antioxidant genes in Caenorhabditis elegans (C. elegans). On the other hand, CFA did not have any role in the lifespan extension of the several mutants linked to the AAK-2/AMPK pathway and it promotes SKN-1 (Skinhead-1) localization into the nucleus, which modulates downstream gene gst-4 (Glutathione S-transferase). In depth investigations revealed that CFA could lower oxidative stress and enhance the lifespan of C. elegans by activating the PAR-4/LKB-1-AAK-2/AMPK-SKN-1/NRF-2 pathway, with crucial involvement of bec-1 and lgg-1 genes for autophagy mediated lifespan extension. This study might contribute to understanding the interactions and mechanisms that allow natural compounds like CFA to treat age-related disorders among several species.

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Coniferaldehyde activates autophagy and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans via par-4/aak-2/skn-1 pathway

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