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Constraints Due to the Interconnected Nature of Cellular Biochemistry in the Evolution of Aging


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Posted 25 May 2022 - 10:22 AM


Why is degenerative aging near universal in the animal kingdom? The present consensus explanation is that natural selection acts most strongly on early reproductive life, selecting for mechanisms that are beneficial at the outset of life, heedless of later life harms when those mechanisms run awry over time. Yet why is it the case that so many of the mechanisms beneficial in young animals are also harmful in older animals? Why is this inevitable? Here it is argued that this is an outcome of the highly interconnected nature of cellular biochemistry. Every protein has many functions and influences the function of many other proteins. It is near impossible to change anything in a cell without impacting many related processes in some way; any change will have many distinct consequences, some of which will be detrimental.

Aging rate differs greatly between species, indicating that the process of senescence is largely genetically determined. Senescence evolves in part due to antagonistic pleiotropy (AP), where selection favors gene variants that increase fitness earlier in life but promote pathology later. Identifying the biological mechanisms by which AP causes senescence is key to understanding the endogenous causes of aging and its attendant diseases. Here we argue that the frequent occurrence of AP as a property of genes reflects the presence of constraint in the biological systems that they specify.

The claim that AP is important in the evolution of aging implies that many genes must exhibit AP. But why should so many genes have this property? The likely answer here lies in the existence of a high degree of biological constraint, arising from the highly integrated nature of biological systems. As Stephen Jay Gould put it, when discussing the evolution of anatomy: "any adaptive change in a complex and integrated organism must engender an automatic (and often substantial) set of architectural byproducts".

This means that a new allele that alters one trait in a way that enhances fitness can easily affect other traits adversely. To use a simple example: for fundamental thermodynamic reasons increasing ATP production rate reduces ATP yield and vice versa. Therefore a mutation increasing ATP production rate will exhibit AP and reduce ATP yield; here ATP yield is traded off against production rate. This illustrates how AP can arise not only from properties of the molecular biology of genes or their RNA or protein products, which tend to be the focus of accounts of pleiotropy, but also from properties of the systems that those products impact.

Link: https://doi.org/10.2...s202205.0212.v1


View the full article at FightAging




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