Illustrating the Potency of Hormesis

Researchers are occasionally surprised when a genetic modification expected to reduce life span in fact extends it. In this example, a defense against lipid peroxidation is disabled in mice. (You might recall that lipid peroxidation is one of the ways in which oxidative damage originating in the mitochondria spreads throughout the body). Rather than reducing the life span of these mice due to greater damage, this actually has the effect of galvanizing further defensive mechanisms to greater activity. So in fact, such a mouse winds up with more effective repair and protection mechanisms over the long term. This is an example of hormesis - regular application of a little damage provokes an ongoing and massive response from the body's repair mechanisms, which leads to a longer healthy life span. From the paper: "The lipid peroxidation product 4-hydroxynonenal (4-HNE) forms as a consequence of oxidative stress. ... A major route of 4-HNE disposal is via glutathione conjugation, in the mouse catalyzed primarily by glutathione transferase mGSTA4-4. Unexpectedly, mGsta4-null mice, in which 4-HNE detoxification is impaired, have an extended life span. This finding could be explained by the observed activation of the transcription factor Nrf2 in the knockout mice, which in turn leads to an induction of [a] detoxification mechanism that contributes to enhanced longevity."



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