The microscopic nematode worms that squirm around in soil and researchers’ labs have a taste for tripe—their own. Their habit of digesting their own intestines helps them reproduce, but it also accelerates their aging, a new study suggests. Those results support an unorthodox hypothesis: Humans and other organisms break down as they get older because traits that benefited them when they are young become harmful.
“It’s a very provocative paper,” says geneticist Keith Blackwell of Harvard Medical School in Boston. “This is telling us that we really need to be paying attention to this idea” about why aging occurs.
Time takes a toll on nematodes. Like many people, the worms, which live about 3 weeks, become obese as they get older. The bodies of elderly worms are jam-packed with fat, which they store in the form of egg yolk. The worms are also prone to uterine tumors, and their intestines wither.
What drives the deterioration of the worms and other organisms? One idea is that aging occurs because molecules such as DNA and proteins accrue damage and start to malfunction. Another possible explanation, known as the run-on hypothesis, holds that organisms break down over time because abilities that help them survive and reproduce early in life continue to “run on” and become a problem later. Certain genes that orchestrate growth and development, for instance, are advantageous for a young animal. But if they continue operating in an older animal, they can promote cancer.
Geneticist David Gems of University College London and colleagues may have discovered a prime example of the run-on hypothesis in action. The team found that nematodes consume their own intestines so they can synthesize yolk for their eggs. The ability to convert the organ into yolk may enable young worms to produce eggs even when food is scarce. But the nematodes keep digesting their intestine even after they stop laying eggs.
This continued self-cannibalization fosters the animals’ aging, Gems and colleagues report today in Current Biology. When the scientists curtailed yolk synthesis by altering certain genes, the animals’ intestines didn’t disintegrate, and the worms didn’t pack on fat. The researchers also found that preventing intestinal breakdown allowed some of the animals to live longer.
Evidence from male nematodes also supports the idea. Male worms are scarce—more than 99% of the animals are hermaphrodites that pump out eggs and sperm. Males don’t normally produce yolk, and as Gems and his team noted, their intestine does not degenerate. But when the researchers genetically modified male worms to manufacture a key yolk protein, the animals began to show two signs of aging they hadn’t shown before: Their intestines deteriorated and they amassed fat.
“When we age, it’s not that we wear out. Our own genes are destroying us,” Gems says. Humans don’t digest their own intestines to make yolk. But run-on processes could also be abetting our aging. One example is the mTOR protein, a master controller of cell metabolism and growth that is necessary during our embryonic development. It remains active in older animals and promotes cancer, neurodegenerative diseases, and other age-related infirmities.
The study “may make people take the [run-on] hypothesis more seriously,” says biogerontologist Steven Austad of the University of Alabama in Birmingham. However, he adds, the findings may only apply to nematodes. “I don’t see the link to mammalian aging.”