Endocrine Abstracts

Research into ageing has been transformed by the discovery of single gene mutations that extend healthy lifespan in laboratory model organisms. Furthermore, the highly conserved, nutrient-sensing, insulin/IGF/TOR signalling network has proved to play a role in ageing in organisms including yeast, invertebrates and mice, and possibly also humans. This signalling network also mediates at least some of the effects of dietary restriction, which also improves health during ageing and extends lifespan in diverse organisms including rhesus monkeys. These interventions can protect against diverse ageing-related loss of function and disease, raising the prospect of the broad-spectrum, preventative medicine for ageing-related disease.

Less well understood are the biochemical mechanisms by which reduced activity of this nutrient-sensing network can improve health during ageing, and the types of ageing-related damage that are ameliorated. For instance, toxic endo- and xenobiothics can be sources of damage. One hypothesis is that the ameliorated ability to metabolize toxic compounds leads to the life span extension. The nuclear hormone receptor DHR96 is a target gene of a key component of the signalling network; it is also involved in xenobiotic metabolism. Manipulation of hormone nuclear receptors in the fly could shed light on this.

Given the highly pleiotropic effects of this signalling network, understanding its role in ageing is crucial for identifying potential drug targets to minimise health benefits with minimal side-effects.