University of Arkansas for Medical Sciences

A Genetic Shortcut to Longevity?

Principal Investigator: Robert Shmookler-Reis

This SRF-supported dauer (nematode worm) lifespan project was part of a portfolio of projects that, rather than specifically developing the seven SENS strands, validate the SENS strategy overall. These projects encompass three broad areas: the comprehensiveness of the seven-strand partitioning of aging, the sociological and economic context of a 'post-aging' world, and the possibility of simpler alternatives to SENS that could impact aging significantly while being more practically feasible in the near term. The University of Arkansas dauer project is in the last of these categories.
 
The consensus view of the evolution of aging is that there is no general program dictating how fast we age: that aging is the collection of gaps in our built-in automatic self-repair processes. This implies that any simple intervention, such as mutating a single gene or administering a chemical, can significantly postpone age-related ill-health only if it gets a lot of "help" from the organism, in the form of genetic machinery that senses the intervention and translates it into a wide variety of specific tweaks to metabolic priorities. But such machinery can only exist if it is also activated by some environmental circumstance that the species in question actually experiences, reasonably often, in the wild - otherwise, the genes in question would never have evolved, or would have mutated into oblivion over generations. Therefore, we can predict that no simple intervention, in any species, will elicit a substantially greater postponement of aging than any such environmental intervention.
 
So, what if we encounter an exception to this "no simple intervention" prediction? Essentially it would suggest that there might be simple ways to postpone human aging substantially after all, even though current data indicates that there are no environmental interventions (specifically, calorie restriction) capable of such a thing. Neglecting to investigate an apparently simple intervention potentially yielding dramatic impact on aging could mean a missed opportunity to save a huge number of lives before SENS could be implemented.
 
The premise of this U. of Arizona work was based on one such promising exception - just one, but a clear one. The nematode worm Caenorhabditis elegans can be induced to live ten times more than normal by mutating one gene, and no one has achieved more than a factor of 3 or 4 by starvation. The "catch" in this premise was that the starvation approach had not actually been studied or tested as thoroughly as it might have been. There were a few circumstantial reasons to suspect starvation could indeed yield 10-fold life extension. The SRF-funded work at the U. of Arkansas aimed to enable the same group that achieved the 10-fold result to try several methods for increasing longevity via starvation. Success with any such method would prove an important proof-of-concept point regarding the potential for single-factor lifespan-increasing interventions to be real and worth devoting further resources to investigate.