Elimination of Unfit Cells Maintains Tissue Health and Prolongs Lifespan

Abstract

SummaryViable 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.

When stem cells grow old: phenotypes and mechanisms of stem cell aging

“…It has also been suggested that stem cell selection during aging is an active process. In flies, cells display their relative fitness with various isoforms of the membrane protein Flower; cells exhibiting lower fitness than their neighbors are culled, and enhancing this process extends maximal lifespan (Merino et al, 2015). Whether similar systems regulate tissue homeostasis and longevity in mammals remains to be explored.…”

Survival of the Fittest: Essential Roles of Cell Competition in Development, Aging, and Cancer

“…Similarly, mouse hematopoietic stem cells can compete in the adult bone narrow when they are exposed to environmental stresses modifying their relative levels of the tumor suppressor p53 [32]. Cell competition can also be triggered by low doses of UV irradiation in Drosophila larvae and in adults [33], where the elimination of damaged suboptimal cells requires the fitness marker Azot. Spontaneous competition occurs in the thymus between incoming T cell progenitors derived from bone marrow and resident thymus progenitors [34].…”

p53 pathway is involved in cell competition during mouse embryogenesis

“…Tissue fitness depends on the elimination of unfit cells (11). In contrast to the classical cell autonomous responses of growth arrest or apoptosis, a noncell autonomous mechanism called cell competition, first uncovered in Drosophila, determines whether a cell is to survive or be eliminated based on its relative "fitness" in comparison with its neighboring cells (12,13).…”