title: Intermittent Stem Cell Cycling Balances Self-Renewal and Senescence of the C. elegans Germ Line.
abstract: Self-renewing organs often experience a decline in function in the course of aging. It is unclear whether chronological age or external factors control this decline, or whether it is driven by stem cell self-renewal-for example, because cycling cells exhaust their replicative capacity and become senescent. Here we assay the relationship between stem cell cycling and senescence in the Caenorhabditis elegans reproductive system, defining this senescence as the progressive decline in "reproductive capacity," i.e. in the number of progeny that can be produced until cessation of reproduction. We show that stem cell cycling diminishes remaining reproductive capacity, at least in part through the DNA damage response. Paradoxically, gonads kept under conditions that preclude reproduction keep cycling and producing cells that undergo apoptosis or are laid as unfertilized gametes, thus squandering reproductive capacity. We show that continued activity is in fact beneficial inasmuch as gonads that are active when reproduction is initiated have more sustained early progeny production. Intriguingly, continued cycling is intermittent-gonads switch between active and dormant states-and in all likelihood stochastic. Other organs face tradeoffs whereby stem cell cycling has the beneficial effect of providing freshly-differentiated cells and the detrimental effect of increasing the likelihood of cancer or senescence; stochastic stem cell cycling may allow for a subset of cells to preserve proliferative potential in old age, which may implement a strategy to deal with uncertainty as to the total amount of proliferation to be undergone over an organism's lifespan.
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cinquin
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Chiang
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Adrian
authors.initials: A
authors.lastname: Paz
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.|Department of Computer Science, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Sam
authors.initials: S
authors.lastname: Hallman
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Oliver
authors.initials: O
authors.lastname: Yuan
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Indre
authors.initials: I
authors.lastname: Vysniauskaite
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.|Department of Computer Science, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Charless C
authors.initials: CC
authors.lastname: Fowlkes
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cinquin
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D000066673:Cell Self Renewal / Q000502:physiology*; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D010053:Ovary / Q000502:physiology; D051716:Replication Protein A / Q000235:genetics; D012098:Reproduction / Q000502:physiology; D013217:Starvation / Q000503:physiopathology; D013234:Stem Cells; D014157:Transcription Factors / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051716:Replication Protein A; C581871:SPE-8 protein, C elegans; D014157:Transcription Factors; C498431:fog-1 protein, C elegans; C492171:fog-2 protein, C elegans