hsf1 (+) extends chronological lifespan through Ecl1 family genes in fission yeast

Abstract

The heat shock factor (HSF), a protein evolutionarily conserved from yeasts to human, regulates the expression of a set of proteins called heat shock proteins (HSPs), many of which function as molecular chaperones. In Saccharomyces cerevisiae, the HSF binds to the 5' upstream region of YGR146C and activates its transcription. YGR146C encodes a functional homolog of ecl1 (+), ecl2 (+), and ecl3 (+) of Schizosaccharomyces pombe. At present, these Ecl1 family genes, which are extenders of chronological lifespan, have been identified only in fungi groups. Based on ChIP analysis, we identified that Hsf1 binds to the upstream DNA region of ecl2 (+) after heat shock in S. pombe. In Caenorhabditis elegans, heat shock factor HSF-1 is known to regulate aging and required for the elongation of longevity by dietary restriction. We found that heat shock factor Hsf1 extends chronological lifespan of S. pombe when overexpressed. Moreover, we show that the extension of chronological lifespan by the overproduction of Hsf1 mainly depends on ecl2 (+) among Ecl1 family genes. From these results, we suggest that HSF is a conserved regulator of lifespan, at least in yeast and nematode, and Ecl1 family genes such as YGR146C and ecl2 (+) are the direct targets of Hsf1 and mediate lifespan extension by Hsf1.