TY - JOUR
T1 - Intercellular competition and the inevitability of multicellular aging
AU - Nelson, Paul
AU - Masel, Joanna
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank Kevin Gomez for making the {f, z}→ {v, c} map rigorous and Jason Bertram for his valuable input on the analytical model. We are also grateful to Daniel Promislow, Athena Atkipis, and two anonymous reviewers for their comments on this manuscript. This research was supported by the John Templeton Foundation (Grant 39667) and the NIH (Grant K12GM000708).
Publisher Copyright:
© 2017, National Academy of Sciences. All rights reserved.
PY - 2017/12/5
Y1 - 2017/12/5
N2 - 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.
AB - 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.
KW - Cancer
KW - Cellular degradation
KW - Cellular robustness
KW - Cooperation
KW - Negligible senescence
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U2 - 10.1073/pnas.1618854114
DO - 10.1073/pnas.1618854114
M3 - Article
C2 - 29087299
AN - SCOPUS:85037039568
SN - 0027-8424
VL - 114
SP - 12982
EP - 12987
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 49
ER -