Centriolar Mechanisms of Differentiation and Replicative Aging of Higher Animal Cells

Abstract

The centrosome (centriole) and the cytoskeleton produced by it are structures, which probably determine differentiation, morphogenesis, and switching on the mechanism of replicative aging in all somatic cells of multicellular animals. The mechanism of such programming of the events seems to include cytoskeleton influences and small RNAs related to the centrosome. 1) If these functions are really related with centrioles, the multicellular organism's cells which: a) initially lack centrioles (e.g., higher plant cells and also zygote and early blastomeres of some animals) or cytoskeleton (e.g., embryonic stem cells); or b) generate centrioles de novo (e.g., zygote and early blastomeres of some animals), will be totipotent and lack replicative aging. Consequently, the absence (constant or temporary) of the structure determining the counting of divisions also means the absence of counting of differentiation processes. 2) Although a particular damage to centrioles or cytoskeleton (e.g., in tumor cells) fails to make the cells totipotent (because the morphogenetic status of these cells, as differentiated from that of totipotent ones, is not zero), but such a transformation can suppress the initiation of the aging mechanism induced by these structures and, thus, make such cells replicatively "immortal".

Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) Finds Patient Age and Sperm Morphology Are Associated With Centriole Quality

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Fission Yeast Does Not Age under Favorable Conditions, but Does So after Stress

“…The existence of an aging lineage can be further supported by the identification of an aging factor that is inherited by the aging cell. Cell components that segregate asymmetrically to aging cells in other organisms, such as the old cell pole [7], protein aggregates [10], ribosomal DNA circles [20], the recently replicated spindle-pole body (new SPB) [21] or centrosome [22], the vacuole, which acidifies with age [23], or even a larger cell volume [24], could be related to aging in S. pombe .…”

Nonpathological Senescence Arises from Unsuitable External Influences

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“…The primary causes of senescence have not been solidly established, though some new concepts have emerged. [1][2][3][4][5] Recently, the hypothesis that aging might be caused by shrinkage of chromosome tips has been rejected by its author. 1 He has recently put forth a new proposal based on hypothetical entities called "redusomes."…”