Worm Offspring Inherit Longevity Even without the Genes

Worms given life-span-enhancing mutations produce offspring that lack the responsible genes but live longer anyway.

The tiny soil-dwelling worms C. elegans, when given mutations that make them live longer, transmit that trait even when their progeny don’t inherit the life-extending mutations. The findings, published online today in Nature, present a modern-day version of Lamarckian inheritance, in which acquired characteristics can be passed to offspring without changes to the genetic code.

Marks of Methuselah: Glowing regions show chemical marks on the genome of C. elegans identical to those in ancestors with life-span-increasing mutations—even though this descendant lacks the mutation.

Although much more research remains to be done, the new study raises the tantalizing possibility that if Grandma practiced caloric restriction—which affects the expression of longevity-enhancing genes—her descendants might reap the benefits.

The inheritance occurs through “epigenetics”: alterations not in the coding sequence of DNA (those ubiquitous A’s, T’s, C’s, and G’s) but in chemical changes that affect whether genes are expressed. One such change involves histones, proteins that act as spools for a cell’s long strands of DNA. Some of the best-known longevity genes, those belonging to the Sir2 family, make proteins that alter histones.

Last year, Anne Brunet of Stanford and colleagues reported that another protein complex, called ASH-2, also alters histones in C. elegans, reconfiguring the histone-DNA complex into an “open” state that promotes gene expression. Deficiencies in ASH-2 extend the worm’s life span by as much as 30 percent.

Brunet says this is likely because, without this protein, the DNA is in a closed configuration and less accessible to the cellular machinery that allows genes to be expressed. “Aging genes may not be as [highly] expressed, which may help prolong life span,” she says.

In the new work, Brunet’s graduate student, Eric Greer, blocked the three key proteins that make up the ASH-2 complex by mutating their genes. As expected, the worms lived longer—typically, an extra seven days beyond their lab life span of 20. Then Greer bred the mutated worms with normal worms until their descendants no longer had the mutations. Nevertheless, the progeny still lived longer, as did their own descendants: even though their genes for the key proteins were normal, an epigenetic memory of longevity persisted. As a result, their DNA was coiled up tight, and their suspected aging genes were sidelined.

“Transgenerational epigenetic inheritance is an area of much controversy,” says Emma Whitelaw, a scientist at the University of Adelaide, who was not involved in the research. “This study will stimulate researchers working with other model organisms to take the notion of transgenerational epigenetic inheritance more seriously.”

It’s not yet clear how broadly the longevity findings will apply. Like C. elegans, animals from yeast to humans have a version of ASH-2. However, much of the aging research in invertebrates has yet to be replicated in more complex animals.

This is not the first time scientists have shown that an acquired trait can be transmitted across generations, as Jean-Baptiste Lamarck postulated two centuries ago. A 2003 study showed that when a female mouse eats DNA-methylating foods, it affects her progeny’s fur color and other traits. A 2010 paper found that when male mice ate high-fat diets, it made their daughters fatter and gave them type 2 diabetes. Another 2010 paper found that changing the cholesterol metabolism in male mice through diet altered their offspring’s cholesterol and lipids. In each case, no DNA mutations were involved—only a trait that the parent acquired and passed on. Whitelaw calls it “a molecular memory of the parent’s experience.”

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