Early life changes in histone landscape protect against age-associated amyloid toxicities through HSF-1-dependent regulation of lipid metabolism.

Transient events during development can exert long-lasting effects on organismal lifespan. Here we demonstrate that exposure of Caenorhabditis elegans to reactive oxygen species during development protects against amyloid-induced proteotoxicity later in life. We show that this protection is initiated by the inactivation of the redox-sensitive H3K4me3-depositing COMPASS complex and conferred by a substantial increase in the heat-shock-independent activity of heat shock factor 1 (HSF-1), a longevity factor known to act predominantly during C. elegans development. We show that depletion of HSF-1 leads to marked rearrangements of the organismal lipid landscape and a significant decrease in mitochondrial ß-oxidation and that both lipid and metabolic changes contribute to the protective effects of HSF-1 against amyloid toxicity. Together, these findings link developmental changes in the histone landscape, HSF-1 activity and lipid metabolism to protection against age-associated amyloid toxicities later in life.

Making room for citizens at the public policy table.

Citizen engagement is a critical factor in determining whether devolution, which shifts responsibility for decision-making from the federal to state and local levels, is a success. Devolved policies and decisions will be more effective when the community members they affect are involved in making them. This article presents six lessons from a citizen-focused project conducted in two communities over two years on what it takes to get and keep citizens involved in the policy process. This project showed that, when applied, these lessons will inspire community members to get involved, create the relationships needed to sustain their involvement over time, and build their capacity to understand and problem solve around complex policy issues.