Worms may age because they cannibalize their

own intestines

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.”