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细胞间竞争与多细胞衰老的必然性。

Intercellular competition and the inevitability of multicellular aging.

机构信息

Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721

Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721.

出版信息

Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):12982-12987. doi: 10.1073/pnas.1618854114. Epub 2017 Oct 30.

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.

摘要

目前的理论将衰老归因于选择失效,这要么是由于多效性限制,要么是由于生殖开始后选择力度的下降。这些理论含蓄地留下了一种可能性,即如果能够识别导致衰老的等位基因,或者如果能够打破拮抗多效性,那么衰老的影响可能会被无限期地减轻或延迟。这些理论是基于多细胞生物之间的选择模型建立的,但要全面理解衰老,还需要研究体细胞选择在生物体内的作用。体细胞(即细胞间竞争)之间的选择可以通过清除无功能细胞来延缓衰老。然而,多细胞生物的适应性不仅取决于其单个细胞的功能如何,还取决于细胞之间的协作程度。虽然细胞间竞争淘汰了无功能的细胞,但它也可能选择那些不合作的细胞。因此,细胞间竞争造成了一种不可避免的两难境地,使得衰老在多细胞生物中不可避免。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2457/5724245/08e96033a673/pnas.1618854114fig01.jpg

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