Clues to aging found in stem cells' genomes

February 13, 2018, Howard Hughes Medical Institute
Clues to aging found in stem cells’ genomes
Repetitive chunks of rDNA genes (black boxes and red rectangles) sprinkled along a chromosome can fold around on themselves, causing rDNA genes to pop out. This loss of genetic material may be related to aging. Credit: K. Lu et al./eLife 2018

Little hints of immortality are lurking in fruit flies' stem cells.

Stem cells that produce sperm use a genetic trick to stay perpetually young across generations, Howard Hughes Medical Institute (HHMI) Investigator Yukiko Yamashita and colleagues have discovered. Certain sections of the fruit fly genome get shorter with age. But remarkably, some can repair the shrinkage, Yamashita's team reports February 13, 2018 in the journal eLife.

This genomic shrinkage may underlie aspects of aging ─ and hint at ways that select cells might thwart it. Until now, scientists had observed the shrinkage phenomenon only in yeast. If the results hold true for humans, they could offer insight into how our cells deteriorate over time.

In the study, Yamashita and her colleagues at the University of Michigan Life Sciences Institute focused on workhorse genes encoded in ribosomal DNA, or rDNA. These genes carry instructions for parts that make up ribosomes, cellular machines that turn RNA molecules into every protein needed in the body.

To make enough of these mission-critical machines, cells need loads of rDNA instruction manuals. Most genes are limited to a single genetic location, but rDNA genes are repeated across multiple spots of the genome. In humans, for instance, five chromosomes contain stretches of rDNA genes, with each spot containing hundreds of repeating copies. This genetic repetition allows cells to churn out enough raw material for ribosomes to keep cells humming.

But the redundancy comes with a cost. Cells can slip up when they copy repetitive DNA strands and divide. "The end result is that some copies are lost every cycle," Yamashita says. "They are popping out of the chromosome."

That loss has been tied to aging for single-celled yeast. But for multicellular organisms, rDNA's role in aging has been a mystery. Yamashita and her colleagues examined rDNA genes in stem cells in the testes of fruit flies. These cells, called germline stem cells, can continuously divide, each time creating a copy of themselves and a sperm cell.

In fruit flies, chains of rDNA genes are found on the X and Y chromosomes. Compared with young male , old males had a shortage of rDNA genes on the Y chromosome ─ leaving them with a shrunken Y chromosome, the researchers discovered.

What's more, this dearth of rDNA seems to be passed on from generation to generation. Geriatric fly fathers (those 40 days old) passed on their reduced number of rDNA genes to their sons, Yamashita and colleagues found. These sons had considerably fewer copies of rDNA than sons born to younger fathers.

Jon Nelson, a researcher in Yukiko Yamashita’s group, uses fruit flies (in flasks at right) to study the role of rDNA in aging. Credit: Yukiko Yamashita

But then the researchers saw something surprising. In many cases, this rDNA loss reversed itself. At about 10 days of age, sons born to old fathers had recovered enough rDNA to be comparable to sons born to young fathers. "This recovery was something we really didn't expect," Yamashita says. The results suggest that rDNA rejuvenation in sons might be a crucial aspect of how stem cells persist from father to son. The researchers don't yet know whether such a reset can also happen to female stem cells in the ovaries.

Though much more work remains, Yamashita suspects that similar resets might be at work in certain kinds of , including and . "Of course, we are not flies," she says, but if pushed to bet, she'd wager that some types of in people can perform the same rejuvenating trick to prevent the rDNA declines that come with age.

These glimpses of perpetual life ─ cells that can refresh themselves as they move down from father to son ─ are what fascinate Yamashita. By finding hints about how certain can continually remain young, the project, "touches upon the secret of ' immortality," she says.

Explore further: Slowing the ageing process—it's in your genes

More information: Kevin L Lu et al. Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells, eLife (2018). DOI: 10.7554/eLife.32421

Related Stories

Slowing the ageing process—it's in your genes

September 5, 2013
Imagine being able to take a drug that can reduce the rate at which you age. Research by Massey University senior lecturer in genetics Dr Austen Ganley is making this dream one step closer to reality.

Missing link in epigenetics could explain conundrum of disease inheritance

July 7, 2016
The process by which a mother's diet during pregnancy can permanently affect her offspring's attributes, such as weight, could be strongly influenced by genetic variation in an unexpected part of the genome, according to ...

Focus on quiescent cells brings to light the essential role of RNA interference in transcription control

November 9, 2016
Some cells just don't get the respect they deserve. In fact, most cells don't. Over 99 percent of the innumerable cells on our planet exist in a state of quiescence. Pick up a handful of soil: it contains thousands of microorganisms, ...

Changes in blood microbiota in obese with liver fibrosis

September 22, 2016
(HealthDay)—In obese patients, changes in blood microbiota are associated with liver fibrosis, according to a study published online Sept. 17 in Hepatology.

Recommended for you

Study of smoking and genetics illuminates complexities of blood pressure

February 15, 2018
Analyzing the genetics and smoking habits of more than half a million people has shed new light on the complexities of controlling blood pressure, according to a study led by researchers at Washington University School of ...

A gene that increases the risk of pancreatic cancer controls inflammation in normal tissue

February 14, 2018
Inflammation is a defensive response of the body to pathogens, but when it persists, it can be harmful, even leading to cancer. Hence, it is crucial to understand the relationship between inflammation and cancer. A group ...

Scientists develop low-cost way to build gene sequences

February 13, 2018
A new technique pioneered by UCLA researchers could enable scientists in any typical biochemistry laboratory to make their own gene sequences for only about $2 per gene. Researchers now generally buy gene sequences from commercial ...

New insights into gene underlying circadian rhythms

February 13, 2018
A genetic modification in a "clock gene" that influences circadian rhythm produced significant changes in the length and magnitude of cycles, providing insight into the complex system and giving scientists a new tool to further ...

Clues to aging found in stem cells' genomes

February 13, 2018
Little hints of immortality are lurking in fruit flies' stem cells.

Gene therapy researchers find viral barcode to cross the blood-brain barrier

February 9, 2018
Gene therapies promise to revolutionize the treatment of many diseases, including neurological diseases such as ALS. But the small viruses that deliver therapeutic genes can have adverse side effects at high doses. UNC School ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.