Research done in the last decade has suggested that limiting energy availability, for example, by dietary restriction, may extend the lifespan of different organisms. Now research from scientists at Elixir Pharmaceuticals provides a molecular sensor that supports this theory. A group headed by Javier Apfeld has found that an increased cellular ratio of two small molecules, AMP and ATP correlates well with increased lifespan in nematode worms. ATP is routinely used by the body as a source of energy and generates AMP as a final product. Apfeld's group focused on an enzyme, called AMP-1, that is specifically activated by high levels of AMP and results in a cascade of reactions that work to conserve energy stores.
Using an array of genetic and molecular tricks on nematode worms, the team demonstrated that animals with extra copies of the AMP-1 enzyme lived on average 13% longer lives than controls. Other experiments demonstrated that environmental stressors that activate the AMP-1 enzyme, also lead to longer lived animals. In addition, animals that were mutant for this enzyme were less able to cope with the same stressors, thus revealing a protective role for this enzyme in dealing with stress.
The group also examined the influence of AMP-1 on other pathways that regulate lifespan in different animals, specifically the insulin like signaling pathways. Experiments revealed that in some cases, AMP-1 activity contributes to longer lives and may work in parallel with previously established molecular players, such as Daf-16, a transcription factor important during insulin signaling.
This study has broad implications for human aging research. Apfeld remarks "The discovery that a sensor of energy levels regulates lifespan is very exciting because it tells us that the worm is actively making a decision in adjusting its lifespan in response to its energy state." The AMP-1 enzyme is highly conserved between nematodes and humans and is part of a molecular circuit that is very similar in both species. Further identification of the targets of AMP-1 will be important in understanding how lifespan is regulated in animals and how it may be controlled and extended therapeutically.
Apfeld leaves us with some food for thought "In humans, AMP-1 is activated in muscle in response to exercise. It is tempting to speculate that perhaps some of the beneficial effects of exercise in human health are the result of the effect of AMP-1 activation on the aging process"
Materials provided by Cold Spring Harbor Laboratory. Note: Content may be edited for style and length.
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