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Intercellular competition and the inevitability of multicellular aging.

Paul NelsonJoanna Masel
Published in: Proceedings of the National Academy of Sciences of the United States of America (2017)
Current theories attribute aging to a failure of selection, due to either pleiotropic constraints or declining strength of selection after the onset of reproduction. These theories implicitly leave open the possibility that if senescence-causing alleles could be identified, or if antagonistic pleiotropy could be broken, the effects of aging might be ameliorated or delayed indefinitely. These theories are built on models of selection between multicellular organisms, but a full understanding of aging also requires examining the role of somatic selection within an organism. Selection between somatic cells (i.e., intercellular competition) can delay aging by purging nonfunctioning cells. However, the fitness of a multicellular organism depends not just on how functional its individual cells are but also on how well cells work together. While intercellular competition weeds out nonfunctional cells, it may also select for cells that do not cooperate. Thus, intercellular competition creates an inescapable double bind that makes aging inevitable in multicellular organisms.
Keyphrases
  • induced apoptosis
  • cell cycle arrest
  • endoplasmic reticulum stress
  • oxidative stress
  • physical activity
  • dna methylation
  • endothelial cells
  • cell proliferation
  • minimally invasive