The lifespan of several model organisms (worms, mice,…) has become somewhat malleable lately. In the past decade or so, methods to extend healthy lifespan have been under investigation, ranging from the identification of relevant genes, to understanding metabolic pathways, to caloric restriction.
A new study uses an engineering approach, as the authors call it. Basically, they combine components, each of which has an effect on the length of life of the study organism, the ever popular flatworm Caenorhabditis elegans.
To begin, the researchers identify potential individual components that could be used in the ‘engineering stage’. This is done in four ways.
- The first one is fairly straightforward and consists out of selecting genes that are already known to extend lifespan.
- Secondly, they went looking for genes that might contribute to known aging pathways.
- A third approach was to look for orthologous genes (genes in different species that can be traced back to a gene in a common ancestor) in zebrafish and humans that act in aging pathways.
- Finally, potential zebrafish anti-aging genes that have functions absent in the worms were selected.
For each of these approaches, the effect on worm lifespan was tested by checking how long the worms lived, as well as studying the effects on cell and whole organism physiology. Each of the four components was able to extend the life of these tiny roundworms by 25 – 50%.
Based on these results, the researchers set out to combine some of the effects elucidated through the above approaches.
Two transgenic worm strains (dual-1 and dual-2) were generated in which two components were combined. Each of the strains contained one worm gene and one zebrafish gene. And what do you know? Lifespan increased by roughly 60 (dual-2) to 80% (dual-1).
Let’s take it a step further, the authors must have thought, as they went on to generate two triple lines, based on the previous dual ones. Triple-1 was based on dual-1, with an extra zebrafish gene, whereas triple-2 was based on dual-2 with an extra worm gene. And, you guessed it, lifespan showed an increase of roughly 85 (triple-2) to 105% (triple-1).
Well, just one more step maybe? One quadruple line was generated, in which basically the two dual lines were combined. So, two worm genes, and two zebrafish ones. Ta-da, lifespan increased with a whopping 125 – 130%, which is quite impressive. Importantly, the worms didn’t just live longer, they do so in good health.
This work provides a proof of principle that one can engineer longer lifespan in C. elegans by adding new components. New technologies in DNA construction, increased knowledge of aging pathways, and improved methods to fine-tuning gene expression will add powerful tools to engineering lifespan… Adding exogenous components from vertebrates is a powerful strategy that goes beyond the natural constraints of the C. elegans genome to engineer worms with increased lifespan and healthspan.
The road from worms to people, of course, is a long one. With serious hurdles. But perhaps not principally beyond our metaphorical walking capabilities? One can’t help but wonder…
Sagi, D., & Kim, S.K. (2012). An Engineering Approach to Extending Lifespan in C. elegans. PLoS Genetics DOI: 10.1371/journal.pgen.1002780