Dietary restriction, which means a reduction of food intake by 40-60% without causing malnutrition can benefit health and extend lifespan of yeast, worms, flies, rodents and perhaps even primates. In the May 31st copy of Nature two papers important insights are given for the mechanism.
After dietary restriction, the small roundworm Caenorhabditis elegans. livses 20-50% longer than their normally fed counterparts. The papers give a role for a pair of evolutionary conserved proteins PHA-4 and SKN-1 which extend survival after dietary restriction in these roundworms. These two proteins are transcription factors, which regulate the expression of many genes. They may also trigger hormones that coordinate physiological responses to dietary restriction.
The PHA-4 protein, was originally described for its role in the development of the pharynx in worm embryos, and is a member of the forkhead family of transcription factors, and is very similar to mammalian FOXA proteins. In mammals, FOXA proteins have developmental roles, and regulate glucose metabolism later in life. The requirement for PHA-4 is very specific.
Panowski and his colleagues also found that a conserved nuclear factor called SMK-1 is required for longevity In addition, dietary restriction triggered the expression of several genes encoding superoxide-dismutase enzymes, which protect animals from oxidative damage — a cause of ageing.
In adult worms, PHA-4 is found in the intestine, gonad and a handful of neurons. Nevertheless, it influences survival of the whole organism, probably by controlling the production of hormones in some of these tissues, which then signal throughout the body.
Mammalian FOXA regulates glucagons which is also released during fasting in higher organisms. Like PHA-4, SKN-1 also functions early in embryonic development, where it specifies the formation of the intestine and related tissues’. Later in life, it helps to protect animals from oxidative stress1″. This transcription factor is related to NRF2 transcription factors, which perform similar functions in mammals’ .SKN-1 is also involved in the food deprivation longevity interaction SKN-1 from neurons is required for the effect on longevity, not the similar form in the intestine.
Dietary restriction increases mitochondial activity, this may be promoted through SKN-1 activity.
This is such exciting news and merits carefully follow up.
Antebi A, 2007, When less is more Nature 447, 536-7
Panowski SH et al 2007, PHA-4/Foxa mediates diet restriction –induced longevity of C elegans . Nature, 447, 550-555
Bishop NA and Guarente L t al 2007 , Two neurons mediate diet restriction – induced
longevity in C-elegan, Nature 447, 545- 549
- Martin Eastwood