Dietary restriction (DR) increases life span in most model systems tested. In mammals, it is associated with health benefits including reduced risk of cancer, cardiovascular diseases and diabetes. In spite of such positive impact, DR is easier to implement in an experimental model as compared to human beings. In this context, it will be beneficial to have an internal model of DR (iDR) where, irrespective of the calorie intake, an organism may enjoy its beneficial effects. We will discuss one such model in C. elegans.
In C. elegans, DR is studied after restricting food intake by using either genetic or non-genetic manipulations. The
eat-2 gene represents a well-studied genetic model of DR where a mutation in a nicotinic acetylcholine receptor subunit leaves the mutant worms with defective pharyngeal pumping and consequently, lower bacterial intake. Non-genetic methods for DR use either serial dilutions or complete deprivation of bacteria. However, these different DR regimes activate distinct pathways. For example,
eat-2 mutants and liquid DR regimes require
pha-4 and
skn-1 transcription factors, being independent of the FOXO homolog,
daf-16. On the other hand, bacterial dilution protocol on solid media requires
daf-16. In this context, identification of genes that induce a DR-like state when manipulated, without the confounding effects of dietary intake, is likely to provide fundamental insights into the mechanisms of DR.
Signalling components within an organism sense low nutrient availability to signal onset of a DR response. In this study, we characterized a novel kinase that qualifies as an important component of the nutrient sensing pathway and a DR response initiator. Knocking down the kinase seems to convince the worms of an imminent nutrient crisis that initiates a state of DR, although food is plentiful, and dramatically increasing life span. We will discuss the molecular mechanism by which this kinase affects longevity and metabolism. This kinase represents a model for DR in mammals without dramatic lifestyle changes.