Aging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

Non-destructive, controllable, remote light-induced release inside cells enables studying time- and space-specific processes in biology. In this work we demonstrate the remote release of tagged proteins in Caenorhabditis elegans (C. elegans) worms using a near-infrared laser light as a trigger from novel hydrogel shells functionalized with silver nanoparticles responsive to laser light. A new type of hydrogel shells was developed capable of withstanding prolonged storage in the lyophilized state to enable the uptake of the shell by worms, which takes place on an agar plate under standard culture conditions. Uptake of the shells by C. elegans was confirmed using confocal laser scanning microscopy, while release from alginate shells in C. elegans and the laser effect on the shells on a substrate in air was followed using fluorescence microscopy. In addition, Raman microscopy was used to track the localization of particles to avoid the influence of autofluorescence. Hierarchical cluster spectral analysis is used to extract information about the biochemical composition of an area of a nematode containing the hydrogel shells, whose Raman signal is enhanced by the SERS (Surface Enhanced Raman Scattering) effect due to hot spots formed by silver nanoparticles present in the shells. The in vivo release demonstrated here can be used to study intestinal microbiota and probiotic compounds as well as a possible future strategy for gene delivery in the worms, other insects and other organisms.

The C. elegans insulin/IGF-1 signaling mutant daf-2 recapitulates the dauer metabolic signature—a shift towards lipid and carbohydrate accumulation—which may be linked to its longevity and stress resistance phenotypes. Trehalose, a disaccharide of glucose, is highly upregulated in daf‑2 mutants and it has been linked to proteome stabilization and protection against heat, cold, desiccation, and hypoxia. Earlier studies suggested that elevated trehalose levels can explain up to 43% of the lifespan extension observed in daf-2 mutants. Here we demonstrate that trehalose accumulation is responsible for increased osmotolerance, and to some degree thermotolerance, rather than longevity in daf-2 mutants. This indicates that particular stress resistance phenotypes can be uncoupled from longevity.