An Example of Lifespan Extension Through Induced Hormesis

Hormesis is the name given to the processes by which a little damage at the cellular level can actually be beneficial, as it spurs repair and maintenance systems to greater efforts - the result is a net gain. Here researchers demonstrate one method of inducing hormesis in nematode worms: "As organisms age, cellular proteins, lipids and nucleic acids sustain damage that can lead to functional deficits in tissues and, ultimately, death. The free radical theory of aging proposes that aging results, at least in part, from damage to cellular components by reactive oxygen species (ROS) ... Indeed, oxidative modification is a major form of damage detected in aging tissues ... Here, we report that hormetic chemicals can be modified to optimize beneficial effects and minimize toxicity in C. elegans, a model for studying aging in whole organisms. C. elegans is well-suited to this problem due to the short lifespan, ease of genetic manipulation and transparent anatomy. First, we examined whether lifespan extension is common among biological toxins with various chemical structures and mechanisms of action. In a small screen of natural phytochemicals, we identified two ROS generating compounds, plumbagin and juglone, which extended lifespan at subtoxic doses. Mean lifespan extension by plumbagin was dependent on SKN-1, a cap'n'collar transcription factor that promotes antioxidant gene expression in response to oxidative stress. We further screened a collection of six plumbagin analogs, identifying three additional naphthoquinones that activated expression of a skn-1 target. One of these could extend lifespan over a larger range of doses than plumbagin, demonstrating the utility of stress hormesis mechanisms as promising prolongevity intervention."


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