The Mystery of Epigenetic Heredity, and Its Possible Impact on Longevity

The basic mechanisms of life and inheritance function much the same in worms, fruit flies, mice, and humans. That is one reason why lower life forms are used so often in longevity research. Much shorter lifespans is another reason. A recent Stanford study on worms provides a hint at an epigenetic method of inheritance which may eventually prove useful for extending lifespans in human offspring.

The study used Caenorhabditis elegans worms with very low levels of the SET-2 enzyme. The SET-2 enzyme normally adds methyl molecules onto DNA's protein packaging material. In doing so, the enzyme opens up the packaging material, allowing the genes to be copied and expressed. Some of those genes appear to be pro-aging genes, says Brunet. Her team knocked out SET-2 by removing genes that code for it. This had the effect of significantly lengthening the worms' lifespan, presumably because those pro-aging genes were no longer expressed.

Next, the long-lived, enzyme-lacking worms mated with normal worms. The offspring had the regular genes for making SET-2, and even expressed normal amounts of the enzyme, but they lived significantly longer than control worms whose parents both had regular lifespans. The life-extending effect carried over into the third generation, but returned to normal by the fourth generation (in the great-grandchildren of the original mutant worms). For the first few generations, having a long-lived ancestor increased life expectancy from 20 days to 25, extending a worm's life by 25 to 30 percent on average.

Brunet and her team haven't yet determined the exact mechanism for the lifetime extension, or which molecules are at work. This is one of the study's imperfections, says David Katz, who researches epigenetic transcriptional memory at Emory University. Regardless, "the effect is clearly epigenetic," he says, "and it's probably one of the most complicated traits that has been linked to epigenetic inheritance."

...The results, published October 19 in Nature (Scientific American is part of Nature Publishing Group), provide the first evidence that some aspects of lifespan length can be passed from parent to offspring, independent of the direct influence DNA. _SciAm

Contrary to what Dr. Katz asserts above, the fact that the research team hasn't determined the exact mechanism for the lifetime extension is one of the study's great promises.

Remember, it is often the questions that a study raises which causes the study to become frequently cited, and immortalised -- not necessarily the questions the study answers. Studies that raise good questions often act as springboards for entire new developments in science. Such may be the case here.