RRC ID 53257
Author Cinquin A, Chiang M, Paz A, Hallman S, Yuan O, Vysniauskaite I, Fowlkes CC, Cinquin O.
Title Intermittent Stem Cell Cycling Balances Self-Renewal and Senescence of the C. elegans Germ Line.
Journal PLoS Genet.
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.
Volume 12(4)
Pages e1005985
Published 2016-4
DOI 10.1371/journal.pgen.1005985
PMID 27077385
PMC PMC4831802
MeSH Aging / physiology* Animals Apoptosis / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Cell Self Renewal / physiology* Cellular Senescence / genetics Cellular Senescence / physiology* DNA Damage / genetics DNA Repair / genetics* DNA-Binding Proteins / genetics Female M Phase Cell Cycle Checkpoints / genetics Ovary / physiology Replication Protein A / genetics Reproduction / physiology Starvation / physiopathology Stem Cells Transcription Factors / genetics
IF 5.224
C.elegans tm1661