Ssk Upregulation Extends Improves Intestinal Function and Extends Life in Flies

In this study, we show that Snakeskin (Ssk), an sSJ-specific protein, plays an important role in controlling the density and composition of the gut microbiota and that upregulation of Ssk during aging can prolong Drosophila lifespan. More specifically, loss of intestinal Ssk in adults leads to rapid-onset intestinal barrier dysfunction, changes in gut morphology, altered expression of antimicrobial peptides (AMPs), and microbial dysbiosis. Critically, we show that these phenotypes, including intestinal barrier dysfunction and dysbiosis, can be reversed upon restored Ssk expression. Consistent with a critical role for intestinal junction proteins in organismal viability, loss of intestinal Ssk in adult animals leads to the rapid depletion of metabolic stores and rapid death. Importantly, restoring Ssk expression in flies showing intestinal barrier dysfunction prevents early-onset mortality. Moreover, intestinal upregulation of Ssk in normal flies protects against microbial translocation, limits age-onset dysbiosis, and prolongs lifespan. Our findings support the idea that occluding junction modulation could prove an effective therapeutic approach to prolong both intestinal and organismal health during aging in other species, including mammals. Link: https://doi.org/10.1016/j.isci.2018.10.022
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs