AgeViva Modulates Inflammatory Responses, Autophagy, and Mitochondrial Homeostasis in BV-2 Cells and C. elegans

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Background: Oxidative stress, neuroinflammation, impaired autophagy, and mitochondrial dysfunction are major contributors to ageing and neurodegenerative diseases. This study investigated whether AgeViva could counteract these processes by modulating redox balance, inflammation, autophagy, and mitochondrial function. Methods: The effects of AgeViva were evaluated using two complementary experimental models: lipopolysaccharide (LPS)-stimulated BV2 microglial cells and Caenorhabditis elegans (C. elegans) nematodes. In BV2 cells, the expression of inflammatory, autophagy-related, and antioxidant response genes, including NRF2, SOD, and GPX, was evaluated by RT-qPCR, while cell viability was assessed by Trypan Blue exclusion assay. In C. elegans, lifespan, healthspan parameters, ROS accumulation, mitochondrial integrity, membrane potential, and the expression of stress-response, longevity, and autophagy-related genes were analyzed following AgeViva supplementation. Results: In LPS-stimulated BV2 cells, AgeViva significantly reduced the expression of mRNA the pro-inflammatory cytokines Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor alpha (TNF-α) while increasing Interleukin-10 (IL-10) levels, AgeViva also induced changes in autophagy-related transcripts, such as modulation of microtubule-associated protein 1a/1b-Light Chain (LC3) and Sequestosome 1 (p62) expression, activated antioxidant-related gene expression, increasing the expression of Superoxide Dismutase 1(SOD1) and Glutathione Peroxidase (GPX). In C. elegans, AgeViva supplementation extended lifespan and improved healthspan parameters, including locomotor activity and pharyngeal pumping. Treated nematodes showed reduced cytosolic and mitochondrial ROS accumulation, preservation of mitochondrial network integrity, and maintenance of mitochondrial-associated fluorescence, reflecting mitochondrial content and/or membrane potential during ageing. Molecular analyses revealed modulation of key pathways involved in stress resistance and longevity, including Insulin-like Growth Factor 1 (Insulin/IGF-1) signaling Dauer Formation-2 and 16 (DAF-2/DAF-16), Skinhead-1 (SKN-1/Nrf2) signaling, and autophagy-related genes, like Ligating (lgg-1), Autophagy-Related-7 (atg-7), Autophagy Related-18 (atg-18), uncoordinated-51 (unc-51), and ectopic p-granules autophagy protein 5 (epg-5). Conclusions: AgeViva promotes healthy ageing by modulating oxidative stress, inflammation, autophagy, and mitochondrial homeostasis.

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