A dicer-related helicase opposes the age-related pathology from SKN-1 activation in ASI neurons.

Unlike activation, an understudied fundamental question across biological systems is how to deactivate a pathway, process, or enzyme after it has been turned on. The irony that the activation of a transcription factor that is meant to be protective can diminish health was first documented by us at the organismal level over a decade ago, but it has long been appreciated that chronic activation of the human ortholog of SKN-1, NRF2, could lead to chemo- and radiation resistance in cancer cells. A colloquial analogy to this biological idea is a sink faucet that has an on valve without a mechanism to shut the water off, which will cause the sink to overflow. Here, we define this off valve.