Stanford University

An Engineering Approach to Increase Lifespan

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The goal of my project is to build a long living worm using a bottom up approach. As model animals to study aging, worms stand out because they are the simplest and have a short lifespan of two weeks. Furthermore, the main pathways found to extend lifespan in worms (i.e. insulin signaling, dietary restriction) are also conserved in mammals.

First, we are using an engineering approach to upgrade the most studied modules that are driving worm aging. These modules include the oxidative damage repair module; energy balance module; stress response module; protein quality control module, which regulates protein turnover; and anti-bacterial defense, which fights bacterial pathogenisity. To extend lifespan by editing each module, we picked genes that are well studied and have the required function to be expressed in worms. In some cases when worms do not have a gene with the proper function, zebrafish genes were expressed. Each module had at least one gene resulting in an increased lifespan, where three were fish genes. For example, to edit energy production and increase lifespan, a fish enzyme, ucp2, was expressed. This enzyme is a specialized version of the one exists in worms and indeed only the fish version was able to make worms live longer.

Second, combining genes that worked individually and eliminating aging sources we were able to increase lifespan almost three fold. In summary, using the knowledge on worm aging and cell biology we were able to pick and combine proper genes to extend worm’s lifespan further and further.