Activated SKN-1 alters the aging trajectories of long-lived Caenorhabditis elegans mutants.

In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here, we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the eat-2 model of dietary restriction, and glp-1-dependent loss of germ cell proliferation.

Activated SKN-1 alters the aging trajectories of long-lived mutants.

In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the model of caloric restriction, and -dependent loss of germ cell proliferation.

Disrupting the SKN-1 homeostat: mechanistic insights and phenotypic outcomes.

The mechanisms that govern maintenance of cellular homeostasis are crucial to the lifespan and healthspan of all living systems. As an organism ages, there is a gradual decline in cellular homeostasis that leads to senescence and death. As an organism lives into advanced age, the cells within will attempt to abate age-related decline by enhancing the activity of cellular stress pathways.

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

Coordination of cellular responses to stress is essential for health across the lifespan. The transcription factor SKN-1 is an essential homeostat that mediates survival in stress-inducing environments and cellular dysfunction, but constitutive activation of SKN-1 drives premature aging thus revealing the importance of turning off cytoprotective pathways. Here, we identify how SKN-1 activation in two ciliated ASI neurons in results in an increase in organismal transcriptional capacity that drives pleiotropic outcomes in peripheral tissues.

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

Unlabelled: Coordination of cellular responses to stress are essential for health across the lifespan. The transcription factor SKN-1 is an essential homeostat that mediates survival in stress-inducing environments and cellular dysfunction, but constitutive activation of SKN-1 drives premature aging thus revealing the importance of turning off cytoprotective pathways. Here we identify how SKN-1 activation in two ciliated ASI neurons in results in an increase in organismal transcriptional capacity that drives pleiotropic outcomes in peripheral tissues.