Sulfated steroid hormones and epigenetic regulation during aging in C. elegans.

Resumen

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 Based on unpublished RNAseq data comparing wild-type and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