Abstract
Removal of the reproductive system of many animals including fish, flies, nematodes, mice and humans can increase lifespan through mechanisms largely unknown. The abrogation of the germline in Caenorhabditis elegans increases longevity by 60% due to a signal emitted from the somatic gonad. Apart from increased longevity, germline-less C. elegans is also resistant to other environmental stressors such as feeding on bacterial pathogens. However, the evolutionary conservation of this pathogen resistance, its genetic basis and an understanding of genes involved in producing this extraordinary survival phenotype are currently unknown. To study these evolutionary aspects we used the necromenic nematode Pristionchus pacificus, which is a genetic model system used in comparison to C. elegans. By ablation of germline precursor cells and subsequent feeding on the pathogen Serratia marcescens we discovered that P. pacificus shows remarkable resistance to bacterial pathogens and that this response is evolutionarily conserved across the Genus Pristionchus. To gain a mechanistic understanding of the increased resistance to bacterial pathogens and longevity in germline-ablated P. pacificus we used whole genome microarrays to profile the transcriptional response comparing germline ablated versus un-ablated animals when fed S. marcescens. We show that lipid metabolism, maintenance of the proteasome, insulin signaling and nuclear pore complexes are essential for germline deficient phenotypes with more than 3,300 genes being differentially expressed. In contrast, gene expression of germline-less P. pacificus on E. coli (longevity) and S. marcescens (immunity) is very similar with only 244 genes differentially expressed indicating that longevity is due to abundant gene expression also involved in immunity. By testing existing mutants of Ppa-DAF-16/FOXO and the nuclear hormone receptor Ppa-DAF-12 we show a conserved function of both genes in resistance to bacterial pathogens and longevity. This is the first study to show that the influence of the reproductive system on extending lifespan and innate immunity is conserved in evolution.
Highlights
Removal or alteration of sexual organs can cause a dramatic increase in lifespan in animals including fish, flies, nematodes, mice and humans, but underlying mechanisms remain unknown
In a novel manner we performed cell ablation of the germline, exposure to bacterial pathogens and used whole genome microarrays of the same animals to find that this resistance is due to expression of genes involved in insulin signaling, nuclear pore complexes, ribosomal translation and lipid production
Using whole genome microarrays comparing unablated and germline ablated P. pacificus we found that resistance to pathogenic bacteria is due to differential expression of genes involved in insulin signaling, pathogen response, lipid metabolism, and core cellular processes like ribosomal translation, proteasome function, nuclear pore complexes
Summary
Removal or alteration of sexual organs can cause a dramatic increase in lifespan in animals including fish, flies, nematodes, mice and humans, but underlying mechanisms remain unknown. In the model organisms Caenorhabditis elegans and Drosophila melanogaster removal of the germline results in an increase in longevity of 40–60% [9,10]. This response depends on several genes including DAF-16/FOXO-like transcription factor, the ankyrin repeat KRI-1, the nuclear hormone receptor DAF-12, the cytochrome P450 DAF-9, the transcription elongation factor TCER-1 [11] and processes such as autophagy, and fat metabolism [12,13,14]. There has never been a systematic analysis of the whole genome transcriptional response to understand what genes are being expressed to decelerate aging and increase lifespan It has been shown in C. elegans that genes affecting lifespan affect other phenotypes such as resistance against bacterial pathogens [15]. This comparative research has revealed evolutionary changes in vulva development [21], gonad morphogenesis [22], and chemosensory behavior [23] compared to C
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