Production of YP170 Vitellogenins Promotes Intestinal Senescence in Caenorhabditis elegans

During aging, etiologies of senescence cause multiple pathologies, leading to morbidity and death. To understand aging requires identification of these etiologies. For example, C. elegans hermaphrodites consume their own intestinal biomass to support yolk production, which in later life drives intestinal atrophy and ectopic yolk deposition. Yolk proteins (vitellogenins) exist as 3 abundant species: YP170, derived from vit-1 - vit-5, and YP115 and YP88, derived from vit-6. Here we show that inhibiting YP170 synthesis leads to a reciprocal increase in YP115/YP88 levels and vice versa, an effect involving post-transcriptional mechanisms. Inhibiting YP170 production alone, despite increasing YP115/YP88 synthesis, reduces intestinal atrophy as much as inhibition of all YP synthesis, which increases lifespan. By contrast, inhibiting YP115/YP88 production alone accelerates intestinal atrophy and reduces lifespan, an effect that is dependent upon increased YP170 production. Thus, despite copious abundance of both YP170 and YP115/YP88, only YP170 production is coupled to intestinal atrophy and shortened lifespan. In addition, increasing levels of YP115/YP88 but not of YP170 increases resistance to oxidative stress; thus, longevity resulting from reduced vitellogenin synthesis is not attributable to oxidative stress resistance.