Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 103, Issue -, Pages 256-267Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2016.12.042
Keywords
2,3-dehydrosilybin A/B; Anti-aging; Anti-aggregation; Anti-oxidation; FGT-1; DAF-16
Funding
- U.S. National Institutes of Health National Center for Research Resources
- Thales GenAge [QALHS AP:10479/3.7.12 MIS380228]
- MAESTRO - European Union (European Social Fund- ESF)
- Greek national funds through the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF)
- Empirikion Foundation
- project of Czech Ministry of Education [LD15081]
- COST Action EU-ROS [BM1203]
- COST (European Cooperation in Science and Technology)
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Aging is an unavoidable process characterized by gradual failure of homeostasis that constitutes a critical risk factor for several age-related disorders. It has been unveiled that manipulation of various key pathways may decelerate the aging progression and the triggering of age-related diseases. As a consequence, the identification of compounds, preferably natural-occurring, administered through diet, with lifespan-extending, anti-aggregation and anti-oxidation properties that in parallel exhibit negligible side-effects is the main goal in the battle against aging. Here we analyze the role of 2,3-dehydrosilybin A/B (DHS A/B), a minor component of silymarin used in a plethora of dietary supplements. This flavonolignan is well-known for its anti-oxidative and neuroprotective properties, among others. We demonstrate that DHS A/B confers oxidative stress resistance not only in human primary cells but also in the context of a multi-cellular aging model, namely Caenorhabditis elegans (C. elegans) where it also promotes lifespan extension. We reveal that these DHS A/B outcomes are FGT-1 and DAF-16 dependent. We additionally demonstrate the anti-aggregation properties of DHS A/B in human cells of nervous origin but also in nematode models of Alzheimer's disease (AD), eventually leading to decelerated progression of AD phenotype. Our results identify DHS A/B as the active component of silymarin extract and propose DHS A/B as a candidate anti-aging and anti-aggregation compound.
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