title: Elimination of unfit cells maintains tissue health and prolongs lifespan.
abstract: Viable yet damaged cells can accumulate during development and aging. Although eliminating those cells may benefit organ function, identification of this less fit cell population remains challenging. Previously, we identified a molecular mechanism, based on "fitness fingerprints" displayed on cell membranes, which allows direct fitness comparison among cells in Drosophila. Here, we study the physiological consequences of efficient cell selection for the whole organism. We find that fitness-based cell culling is naturally used to maintain tissue health, delay aging, and extend lifespan in Drosophila. We identify a gene, azot, which ensures the elimination of less fit cells. Lack of azot increases morphological malformations and susceptibility to random mutations and accelerates tissue degeneration. On the contrary, improving the efficiency of cell selection is beneficial for tissue health and extends lifespan.
authors.affiliation: Institute of Cell Biology, IZB, University of Bern, Bern 3012, Switzerland.
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Merino
authors.affiliation: Institute of Cell Biology, IZB, University of Bern, Bern 3012, Switzerland.
authors.forename: Christa
authors.initials: C
authors.lastname: Rhiner
authors.affiliation: Institute of Cell Biology, IZB, University of Bern, Bern 3012, Switzerland; Polarity Division and Morphogenesis, Institut Curie, CNRS UMR 3215, INSERM U934 Paris, France.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Lopez-Gay
authors.affiliation: Institute of Cell Biology, IZB, University of Bern, Bern 3012, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Buechel
authors.affiliation: Institute of Cell Biology, IZB, University of Bern, Bern 3012, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hauert
authors.affiliation: Institute of Cell Biology, IZB, University of Bern, Bern 3012, Switzerland. Electronic address: emoreno@izb.unibe.ch.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moreno
mesh_terms: D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D008136:Longevity; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment
chemical_list: C000597193:Azot protein, Drosophila; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins