Intercellular competition and the inevitability of multicellular aging

Paul Nelson and Joanna Masel
PNAS December 5, 2017 114 (49) 12982-12987; published ahead of print October 30, 2017 https://doi.org/10.1073/pnas.1618854114

  1. Edited by Raghavendra Gadagkar, Indian Institute of Science, Bangalore, India, and approved October 6, 2017 (received for review November 14, 2016)

See related content:

See related content:

This article has a reply. Please see:

Significance

We lay out the first general model of the interplay between intercellular competition, aging, and cancer. Our model shows that aging is a fundamental feature of multicellular life. Current understanding of the evolution of aging holds that aging is due to the weakness of selection to remove alleles that increase mortality only late in life. Our model, while fully compatible with current theory, makes a stronger statement: Multicellular organisms would age even if selection were perfect. These results inform how we think about the evolution of aging and the role of intercellular competition in senescence and cancer.

Abstract

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.

Footnotes

  • ↵1To whom correspondence should be addressed. Email: pgnelson{at}email.arizona.edu.
View Full Text
Back to top
Article Alerts
Email Article
Citation Tools
Request Permissions
Inevitability of multicellular aging
Paul Nelson, Joanna Masel
Proceedings of the National Academy of Sciences Dec 2017, 114 (49) 12982-12987; DOI: 10.1073/pnas.1618854114
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Proceedings of the National Academy of Sciences: 116 (7)
Current Issue

Submit

Jump to section

You May Also be Interested in

Nonmonogamous strawberry poison frog (Oophaga pumilio). Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Putative signature of monogamy
A study suggests a putative gene-expression hallmark common to monogamous male vertebrates of some species, namely cichlid fishes, dendrobatid frogs, passeroid songbirds, common voles, and deer mice, and identifies 24 candidate genes potentially associated with monogamy.
Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Active lifestyles. Image courtesy of Pixabay/MabelAmber.
Meaningful life tied to healthy aging
Physical and social well-being in old age are linked to self-assessments of life worth, and a spectrum of behavioral, economic, health, and social variables may influence whether aging individuals believe they are leading meaningful lives.
Image courtesy of Pixabay/MabelAmber.