The discovery in the 1990s that a mutation in a single gene of an experimental worm could double its lifespan set off a stampede of research on the molecular biology of ageing and triggered hopes that drug therapies or other interventions could be developed to extend healthy human lifespan. But as is often the case in science, the genetic regulation of ageing is more complicated than it first appeared.

The nature of this complexity is illuminated in a new paper which describes the mechanisms by which longevity is regulated post-transcriptionally, or after a genetic blueprint has been transcribed from an organism’s DNA. The identification of these mechanisms will serve as a road map for screening new, more specific drugs to prolong healthy lifespan.

The research was conducted in C. elegans, a tiny nematode worm that is a popular model in aging research because of its genetic similarity to humans and because of its short lifespan, which allows scientists to easily study lifespan-extending interventions.

The scientists used bioinformatics, or data analysis, techniques to compare genes in worms fed normal diets with those whose diets were restricted.

Dietary restriction, or DR, which refers to calorie restriction without malnutrition, is the most robust intervention known for extending lifespan, and has been demonstrated to increase lifespan and delay the onset of age-related degenerative disease in a wide range of species, from one-celled yeasts to primates.

The scientific evidence on the lifespan-prolonging effects of DR has ignited a quest to develop “DR mimetics,” or drugs that mimic the effects of DR without the need to dramatically reduce calories. In addition to being difficult to adhere to, such a diet is associated with negative side effects including increased sensitivity to cold and loss of energy and libido. The identification of these new mechanisms opens up the possibility of developing new, more precise DR mimetics.

Can you imagine a time when human life expectancy could double?