An Engineering Approach to Extending Lifespan in Nematodes

If more life science researchers thought like engineers, we might see faster progress towards extended healthy longevity. One of the marks of pure engineering versus pure science is the willingness to pursue development of working solutions in the absence of full knowledge of the underlying principles. Both the Romans and the early British industrialists built superb bridges in the absence of a full understanding of structural and material science, not by chance but because they could deliberately and carefully use empirical knowledge to work around their ignorance of deeper scientific laws. So too there is much more room for empiricism in the development of medicine, and in longevity science in particular, than is presently practiced. In the scientific world, the favored next step following a demonstration of extended life in laboratory animals is to figure out every detail of how it works rather than explore the possibility of building a therapy - but both paths could be explored in parallel.

In any case, here are results from a group of life science engineers, working with nematode worms:

We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add [components from other species].

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We overexpressed five genes that act in endogenous worm aging pathways, as well as two genes from zebrafish encoding molecular functions not normally present in worms. For example, we used zebrafish genes to alter mitochondrial function and innate immunity in ways not normally available to C. elegans and extended worm lifespan by ~40%. Next, we used a modular approach to extend lifespan by 130% by combining up to four components in the same strain. These results provide a platform to build worms having progressively longer lifespans.

This project is conceptually similar to using engineering to increase the useful lifespan of a primitive machine (1931 Model T) using both parts from the model T as well as parts from a more advanced machine (2012 Toyota Corolla). Our results open the door to use engineering to go beyond the constraints of the C. elegans genome to extend its lifespan by adding non-native components.

Tinkering with metabolism and genes to slow aging isn't my favored approach for extending healthy longevity - it is a poor path in comparison to efforts aimed at repairing accumulated damage - but I am very much in support of the attitude displayed by the authors quoted above. The research community could do with a whole lot more of that sort of mindset.