RT Journal Article
SR Electronic
T1 Deficiency for Piwi results in transmission of a heritable stress that promotes longevity via DAF-16/Foxo
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 326769
DO 10.1101/326769
A1 Bree Heestand
A1 Matt Simon
A1 Stephen Frenk
A1 Shawn Ahmed
YR 2018
UL http://biorxiv.org/content/early/2018/05/19/326769.abstract
AB The C. elegans Piwi Argonaute protein PRG-1 and associated piRNAs protect the genomes of germ cells by suppressing the expression of transposons and potentially deleterious foreign nucleic acids. Deficiency for prg-1 compromises germ cell immortality, resulting in normal fertility for many generations followed by progressively reduced fertility and ultimately sterility. The sterility phenotype of prg-1 mutants was recently shown to be a form of reproductive arrest, which implies that prg-1 mutants may become sterile in response to a form of heritable stress. The DAF-16 stress resistance and longevity factor can promote germ cell immortality of prg-1 mutants by activating a systemic RNAi pathway. We found that this RNAi pathway was not required for the somatic longevity function of DAF-16. Given that prg-1 mutant germ cells may transmit a form of heritable stress, we studied the somatic longevity of prg-1 mutant adults. We found that early generation prg-1 mutants had normal lifespans, but that late-generation adults that displayed reduced fertility or sterility were long lived. Germ cells of long-lived late-generation prg-1 mutants gave rise to F1 cross progeny that were heterozygous for prg-1, fertile and also long lived. However, in the absence of DAF-16, the heritable stress transmitted by prg-1 mutant germ cells was deleterious and caused lifespan to shorten. We conclude that deficiency for the genomic surveillance factor PRG-1/Piwi results in germ cells that transmit a heritable stress that promotes somatic longevity via DAF-16/Foxo, which could be relevant transgenerational regulationof aging.