Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Edited by Raghavendra Gadagkar, Indian Institute of Science, Bangalore, India, and approved October 6, 2017 (received for review November 14, 2016)
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.
Author contributions: P.N. and J.M. designed research; P.N. performed research; P.N. analyzed data; and P.N. and J.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
See Commentary on page 12851.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1618854114/-/DCSupplemental.
- Copyright © 2017 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Inevitability of multicellular aging
Article Classifications
- Biological Sciences
- Evolution
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.
See related content: