The C. elegans Piwi Argonaute protein PRG-1 associated with piRNAs to preventing germ cells from expressing foreign genetic elements such as transposons. PRG-1 promotes germ cell immortality and lines of
prg-1 mutants are initially fertile but become sterile if they are grown for many generations.
prg-1 mutant sterility is a form of reproductive arrest (1), which may resemble reproductive arrest in response to environmental stresses such as starvation (2). We found that early-generation
prg-1 mutants have normal lifespans and fertility, while later generations had reduced fertility yet longer lifespans. Mutation of the stress response transcription factor Daf-16/FOXO, caused the longevity phenotype of late-generation
prg-1 mutants to disappear, leading to the conclusion that
prg-1 mutant longevity may be a hormetic stress response. Phenotypes that arise from epigenetic defects can be inherited for at least 3 generations (3,4), and we found that longevity of late-generation
prg-1 mutants is inherited by F1 but not F2 cross progeny. We are currently asking if the
daf-12 germline signaling pathway that regulates aging is required of
prg-1 mutant longevity. Overall, our results imply that the longevity of late-generation
prg-1 mutant is distinct from the longevity that is transmitted for several generations by germ cells of mutants deficient for the ASH-2/SET-2/trithorax transcriptional activation complex (3,4). 1. Heestand, B., Simon, M., Frenk, S., Titov, D. & Ahmed, S. Transgenerational Sterility of Piwi Mutants Represents a Dynamic Form of Adult Reproductive Diapause. Cell Rep. 23, 156-171 (2018). 2. Angelo, G. & Van Gilst, M. R. Starvation Protects Germline Stem Cells and Extends Reproductive Longevity in C. elegans. Science 326, 954-958 (2009). 3. Greer, E. L. et al. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479, 365-371 (2011). 4. Lee TW, David HS, Engstrom AK, Carpenter BS, Katz DJ. Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans. Elife (2019). doi: 10.7554/eLife.48498