AI Article Synopsis
- Aging leads to a decline in physiological functions across all organisms, but environmental factors like diet can influence this process.
- The compound nordihydroguaiaretic acid (NDGA) has been shown to increase lifespan in both flies and mice, although its exact mechanism of action is not well understood.
- Research reveals that NDGA inhibits the p300 epigenetic regulator, blocking its acetyltransferase activity and promoting autophagy, which helps explain how NDGA may contribute to increased longevity.
Article Abstract
Aging is characterized by the progressive loss of physiological function in all organisms. Remarkably, the aging process can be modulated by environmental modifications, including diet and small molecules. The natural compound nordihydroguaiaretic acid (NDGA) robustly increases lifespan in flies and mice, but its mechanism of action remains unclear. Here, we report that NDGA is an inhibitor of the epigenetic regulator p300. We find that NDGA inhibits p300 acetyltransferase activity in vitro and suppresses acetylation of a key p300 target in histones (i.e., H3K27) in cells. We use the cellular thermal shift assay to uniquely demonstrate NDGA binding to p300 in cells. Finally, in agreement with recent findings indicating that p300 is a potent blocker of autophagy, we show that NDGA treatment induces autophagy. These findings identify p300 as a target of NDGA and provide mechanistic insight into its role in longevity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775102 | PMC |
| http://dx.doi.org/10.1038/s41514-019-0037-7 | DOI Listing |
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