Intercellular Competition and Inevitability of Multicellular Aging (PNAS, 2017)

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. 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.

About Robert Zinn

Robert Zinn, M.D., Ph.D. is a medical doctor, physician, and web entrepreneur, who, for over 15 years was employed by academic and research institutions and focused his clinical practices on very specialized patient populations, such as those with rare genetic diseases or rare cancers. He shares his knowledge through his website,

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