Previous studies have found that mice, yeast, flies, and other animal species all live longer when their caloric intake was restricted by about 60% while keeping normal levels of vital nutrients. Unfortunately, the reason why this happened has not been found in over 70 years of study.
However, Andrew Dillin and fellow researchers, while studying nematode worms (scientific species name:
Caenorhabditis elegans) found out the reason! The gene
pha-4.
They experimented with the worms and discovered that eating too much reduced the worms’ life span, while a diet that tended toward starvation also limited the life span of the worms. The restricted diet, but still with sufficient vital nutrients, was just right—and produced longer living worms.
Dillin’s team tried different things. They removed the pha-4 gene from some of the worms, but found that its removal did not make the worms live longer while on the restricted diet. They also increased the level of the pha-4 gene in the body of the worms, while on the restricted diet. This action produced longer living worms.
It is thought that the pha-4 gene is the first gene that shows a relationship with living longer and eating a restricted diet.
Further research with this gene will attempt to learn the molecular mechanism by which pha-4 works (that is, providing longer life when organisms are placed on a restrictive diet).
Such studies with worms and other animals are expected to help humans live longer, too, because people possess genes very similar to pha-4 in worms. However, the human system is much more complicated than many of these test subjects. So, whether their conclusions will help us live longer or not will be determined in the future. It is not known yet.
If the research does help humans live longer, it may pave the way for slowing down age-related diseases such as Alzheimer’s. In fact, scientists are hoping to develop a drug that could some day imitate the way that pha-4 works without people having to eat a drastically reduced amount of food each day.
Although research is still in the early stages, many people around the world are using calorie restricted diets in the hopes that they will live longer. For example, the Calorie Restriction Society, based in California, recommends its members eat less than half of the recommended calories each day. Many of these restricted diets recommend about 60 to 70% less calories than what is recommended. For the average adult in the United States, this would be about 700 calories in comparison to a 2,000-calorie diet for an adult woman (assuming 65% of what is recommended) and about 890 calories in a 2,550-calorie diet for an adult men.
The conclusions of Dillon and fellow collaborators were written up this week in the journal
Nature.
有关PHA-4基因先前的研究信息：
- PHA-4 has striking similarity to Drosophila fork head and the mammalian HNF-3abg genes in protein sequence, expression patterns and mutant phenotype.
- As shown by the Mango Lab, pha-4 mutants have pharynx and rectum development blocked early in embryogenesis.
- pha-4 is expressed in all pharyngeal and rectal cells, beginning at the earliest stages. It is also expressed at lower levels in the gut.
- pha-4 activates at least two genes in the pharyngeal muscle development pathway: ceh-22, a NK-2 class transcription factor, and myo-2, a pharyngeal myosin. Ectopic expression of pha-4 by a heat shock promoter leads to ectopic expression of pharyngeal myosin (arrow).
- We propose that the combination of pha-4 and regulatory molecules such as the homeobox gene ceh-22 produce the specific gene expression patterns in all cell types during pharynx development.
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