University stem cell research could have implications in aging

University of Michigan researchers from the Life Sciences Institute have found that ribosomal DNA, also known as rDNA, in the testes of male fruit flies rejuvenate after being passed onto offspring. University researchers say this could open doors for further stem cell research on aging.

RDNA is responsible for carrying the code that makes up ribosomal RNA, which are the molecular machines that turn messenger RNA into proteins.

The rDNA genes repeat in the genome so cells can keep working, but are also highly unstable. Sometimes, cells will divide when copying DNA strands, resulting in a loss of copies. 

Medical student Kevin Lu has conducted research with the Biology Prof. Yukiko Yamashita’s Lab and said rDNA has a much smaller physical presence in the fruit fly anatomy as the fruit flies age.

“As the stem cells in the animal get older and older, these repetitive areas called ribosomal DNA are destabilized, they get smaller and smaller and they shrink within the lifespan of the organism itself,” Lu said.

Jonathan Nelson, a postdoctoral researcher with the Yamashita Lab, explained while the aging process and loss of copies have been connected in the past for single-celled yeast organisms, less is understood with regard to multicellular organisms.

“We expected to find this aging to happen, it’s been shown before in yeast,” Nelson said. “But it’s never been shown before in an animal, in something multi-celled.”

By examining the stem cells found in male fruit flies, Yamashita’s research team found older males had smaller Y chromosomes in comparison to younger males as a result of the loss of rDNA genes over time.

The male offspring of older males then received fewer copies of rDNA genes than those of younger males. What was most surprising to the researchers was these cells’ ability to recover from the loss. Within 10 days, male offspring born to older fathers had a similar amount of rDNA as those born to young fathers. By expanding their own DNA, these male offspring ensured the next generation had a normal amount of DNA.

In an email interview, Natalie Warsinger-Pepe, a graduate student in molecular and integrative physiology, said the discovery of self-generating stem cells could explain how some species have managed to survive even with stem cells that lose their size over time.

“Even though some of the rDNA is lost during aging in the germline, future generations are able to recover the original amount of rDNA in their germline,” Warsinger-Pepe wrote. “This is really cool because there are mechanisms at play that have evolved to protect this highly unstable region that is essential for life and ensure that future generations (and thus a whole species) (sic) won’t quickly die off for lack of rDNA.”

According to Nelson, the discovery of this rejuvenation may lead to questions about how the impact of aging can be lessened, and whether or not cancer cells use the same tools to multiply themselves indefinitely.

“The reason why they’re cancers is because they’re dividing a lot,” Nelson said. “If we identify what’s happening in those cancer cell conditions, then we might be able to identify new ways to try and combat cells that are dividing too much and creating cancers.”

Biology Prof. Yukiko Yamashita, an investigator for the Howard Hughes Medical Institute, emphasized in an email interview the need for a natural course of discovery in scientific research.

“Science is not an industrial project,” Yamashita wrote. “We can’t decide what to expand and shrink. Discoveries will lead us where to go.”

Lu maintained this breakthrough is a clue that will lead to further discoveries in the field of stem cell research.

“When you do research like this, it always gives us hints to things that can underlie the costs of aging,” Lu said. “But what it is is a hint. And there needs to be a lot more work done in it before we can cure aging.”