In Worms, Genetic Clues to Extending Longevity [NYT]
By NICHOLAS WADE
Published: June 8, 2009
People die, but one part of them, at least in principle, is immortal. In the germline cells that produce eggs or sperm, biological time stands still. This is why babies are all born with the same age, the clock set to zero, regardless of the age of their parents.
A little piece of the germline’s immortality, it now seems, can be acquired by the ordinary cells of the body, and used to give the organism extra longevity.
This is the conclusion of a research group at the Massachusetts General Hospital led by Sean P. Curran and Gary Ruvkun. Their studies were carried out in the laboratory round worm, C. elegans, but many of the discoveries later turned out to apply to people, too.
The finding may provide an explanation for the many recent experiments in which biologists have made laboratory organisms live longer by manipulating their genes. Most of these genes lie in what is known as the insulin-signaling pathway, which influences the body’s metabolism of fat and glucose.
When the pathway is disturbed, by deactivating one of its genes, the animal generally lives longer. The effect seems similar to the extension of life span enjoyed by laboratory mice when they are kept on a diet very low in calories.
The insulin-signaling pathway activates a powerful gene regulator that controls many genetic pathways, including some that govern metabolism. Dr. Ruvkun’s team reports in Nature
nature.com
a novel effect of the regulator: It can switch on in the worm’s ordinary body cells, or somatic cells, two genes that are usually active only in the germline cells and are kept permanently switched off in the somatic cells.
These two genes protect the cells’ DNA by reducing protein synthesis and cranking up the worm’s equivalent of an immune system.
Higher-level protection of DNA is presumably one key to the germline cells’ immortality. “This ability for somatic cells to gain a stemlike character could be really important in extending life span,” Dr. Ruvkun said.
This seems to be the first time that increased longevity has been attributed to a mechanism borrowed from the germ cells’ defenses against mortality. “This is, I believe, brand new,” said Steven Austad, a longevity expert at the University of Texas Health Science Center.
Understanding the pattern of gene activity in germline cells “might provide particularly helpful clues as to how best to protect somatic cells from aging damage,” he said.
The master regulator gene studied by Dr. Ruvkun’s team is called daf-16 in worms and FOXO in mammals. Other researchers may now explore whether the FOXO genes in mice and people can also turn on the germline pathways in somatic cells.
“The idea that somatic cells maintain the potential to reacquire pathways lost during differentiation is tantalizing,” Dr. Ruvkun writes, and it
nytimes.com |
