Resumen de Sulfated steroid hormones and epigenetic regulation during aging in C. elegans.
Using the nematode C. elegans as a model [1], previous lab work demostrated that increased levels of sulfatedsteroid hormones (SHs) extend lifespan and ameliorate age-associated neurodegenerative disorders [2]. This wasachieved by knocking out or inhibiting sul-2, the enzyme involved in the removal of the sulfate moiety of sulfatedSHs. Currently, one of the main aims of the laboratory is to understand the molecular mechanisms triggered bysulfated SHs responsible for this health improvement. Based on unpublished RNAseq data comparing wild-type andsul-2 C. elegans, we found that some of the transcriptional consequences observed in sul-2 mutants resembled thosefound in hpl-2 and his-24 mutants. hpl-2 and his-24 encode proteins important for heterochromatin formation andcompaction [3], suggesting the involvement of epigenetic deregulation in health benefits mediated by increasedlevels of sulfated SHs. Furthermore, many of the more differentially expressed genes in sul-2 mutants localized closeto each other, forming clusters, providing further evidence of a possible role of epigenetic regulators in mediating thesulfated SHs response. Using genetic and chemical approaches, the objective of this master project was to elucidatethe putative roles of hpl-2 and his-24 in lifespan extension and neurodegenerative protection induced by sulfatedSHs.
