Fountain of Age

UNC-TV Science: May 8, 2014
The Fountain of Age

Your cells are a lot like a pair of jeans. For the most part, they do their job without too much fuss. They cover you up and take the beating that everyday life throws at them: the wear, the dirt and the wash.

But much like even the best pairs of jeans, cells break down and eventually die and as cells fail to replace themselves in our tissues, we age.

But a new study from the UNC School of Medicine and the University of Cambridge shows that wear and tear may not be the only things that determine how quickly your cells deteriorate. In fact, you might inherit some of that age from your great great grandparents.

NematodeMatt Simon, a graduate student at UNC and co-first author of the study, stumbled upon this age-maker while investigating the sex cells of nematodes (tiny worms). Normally, those sex cells achieve the closest thing to immortality: as they get passed down from generation to generation, they work just as well every time.

But a mutation in a specific mechanism called Piwi/piRNA, which has the job of making sure a certain segment of the nematode’s DNA never gets expressed, causes the nematodes to become more and more infertile as it gets passed down. Simon also found that by limiting a completely separate signal mechanism in the nematode sex cells, they could restore that sex cell immortality.

That second pathway has the added side effect that it makes the non-sex cells, or somatic cells, wear out more slowly. So not only do the nematodes get their sex-cell immortality back but they also live longer.

The fact that Piwi/piRNA doesn’t cause infertility in one shot is significant. Whatever the malfunction is causing has to pile up for a few generations before the nematode becomes completely infertile. It looks more like an epigenetic change, or something that gets passed down without being a direct change to the DNA itself.

In humans, some neurodegenerative disorders, Huntington’s chorea for example, look similar. That is, in some cases of Huntington’s, which usually onsets between the ages of 30 and 50, many children of men with Huntington’s had a younger onset age than their fathers did.

That concept is called anticipation, and Simon theorizes in the new paper that the nematodes undergo an epigenetic anticipation, where the effects on the parents’ sex cells get passed down and multiplied every generation.

This is where a possible parallel to human somatic cells arises. Older mammal cells undergo a similar aging process, where a pathway responsible for silencing a specific section of DNA malfunctions. Simon writes in the paper that because of this, there’s a shot that the same sort of epigenetic anticipation could be what causes our somatic cells to age.

Going back to blue jeans, as you age, your cells pass down more and more products of malfunctioning pathways while they reproduce, so in effect your new jeans are becoming slightly less new every time you get a new pair.

And the kicker is, these malfunctions may get passed down from organism to organism as well. That is, it’s possible that you could be getting worn hand-me-down cell jeans from your ancestors that determine how your cell jeans will wear with age.

Now, an important point to bear in mind is that one study in nematodes hasn’t cracked the code on how human cells age. Far from it, in fact, and Simon writes in the paper that the epigenetic anticipation connection to humans is speculative at this point. It is, however, an exciting direction for cell scientists to investigate in terms of human aging. The paper was published in the journal Cell Reports.

- Daniel Lane

Daniel Lane covers science, medicine and the environment as a reporter/writer. He is currently pursuing a master's degree in medical and science journalism at UNC - Chapel Hill.