On the relationships between the rate of cytoskeletal stable assemblies turnover, stability of the differentiated state, development and aging.
There is a general consensus that biological specificity is a structure-derived property. If a living system is going to maintain its structure and function then the newly synthesized molecules should replace the faulty ones at the correct time and in the correct places so that the previously established cellular topology will be preserved. In addition, pre-existing spatial determinants which will direct the asymmetrical assembly of the newly synthesized molecules should be available. Therefore, regulation of turnover of cellular architecture represents an essential feature of living systems. In considering the underlying causes of cellular senescence it seemed reasonable to focus on the relationship between development of a stable phenotype and the turnover of cellular and extracellular stable assemblies, currently thought to be involved in maintaining the stability of the differentiated state. In recent years evidence has accumulated suggesting a reciprocal relationship between cytoarchitecture turnover rate and achievement of a stable structure. The lack of a feedback control on the turnover of cellular stable assemblies and/or a low turnover rate of cytoarchitecture components would mean that they will be subjected to damaging processes such as oxidation, cross-linking, aminoacid racemization or non-enzymatic browning which are known to occur in other long-lived proteins. The consequence would be the generation, with advancing age, of faulty cellular structures which, in turn, would alter the deposition of newly synthesized molecules. This process may lead to a progressive breakdown in cellular and extracellular stable structures. The process of directed assembly seems to be general for biological systems displaying history-dependent development. We believe that it is this strategy which imposes severe limitations on presegregated spatial determinants turnover rates and, therefore plays a major role in initiating the aging process. We also suggest that species-specific life-span might be determined by the species-specific regulatory networks which governs the cell-specific cytoarchitecture damaging rate. Moreover, aging appears to be an intrinsic feature of biological systems displaying history-dependent development and should be absent in systems displaying history-independent life-cycles, such as bacteria, some species of protozoa, and certain transformed cell lines. An important feature of protein turnover is that this process requires metabolic energy. Therefore, we can expect that structure preservation strategy is a part of a more general energy-saving strategy, a view previously expressed by T.B.L. Kirkwood (Nature, Lond., 1977, 270, 301-304).
Wagner
A P
AP
Department of Biochemistry, University of Karlsruhe, West Germany.
D000375:Aging / Q000473:pathology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D003896:Desmosomes / Q000378:metabolism; D004734:Energy Metabolism; D004905:Erythrocyte Aging; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008136:Longevity; D008954:Models, Biological; D009024:Morphogenesis; D009414:Nerve Growth Factors / Q000494:pharmacology; D013045:Species Specificity; D014404:Tubulin / Q000096:biosynthesis
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D009414:Nerve Growth Factors; D014404:Tubulin