Dynamic telomeres and the aging process

My name is Sara Wilbur. I’m a third-year masters student in biology at the University of Alaska Fairbanks.

IMG_20170312_122527159 (1).jpg
Me and my dog Junie biking the White Mountains trail. Photo credit: Jason Clark.

I’ve written for NiB before, about work-life balance in academia, and yesterday I was introduced as the newest contributor to NiB. I’m very excited to write for this wonderful project! You can expect future articles to focus on telomeres, arctic ground squirrels/hibernation, and scientific life in Alaska.

Aging, DNA structure, and the dynamic telomere

The mind simplifies difficult concepts to support graspability. One example of this tendency is found in our attempts to define the aging process. Aging is complex, nuanced, and expressed differently across individuals. It would be quite useful if there was a quantifiable “thing” in the body that indicated how long an organism had left to live. In the mid-1970s, a discovery came that presented itself as a solution to the problem of measuring age: protective, terminal chromosome sequences known as telomeres.

2930423615_5320362dea_o.jpgAging is complex and nuanced. Photo credit: Flickr.

As is widely understood, DNA provides the molecular “blueprint” for all organisms, influencing what they look like and how they behave. The particular nucleic acid sequences (the Ts, As, Gs, and Cs) of an individual’s DNA codes for specific proteins, which are involved in virtually every cellular process. However, of all the DNA you have, only 1% of DNA contains coding sections. Initially considered “junk DNA,” the remaining 99% of noncoding DNA fulfills many important functions, including transcriptional regulation (turning genes “up” to make more of a particular protein or “down” to lessen protein production) and DNA protection, a duty fulfilled by the dynamic telomere.

Telomeric duties

Telomeres have two main purposes. One is to maintain chromosome integrity. If you’re a molecule of DNA, a double-strand break is cause for alarm. Fortunately, DNA repair enzymes are recruited to double-strand breaks, allowing DNA to replicate properly and be transcribed faithfully. However, if you think about it, a chromosome end could be seen as a double-strand break. What prevents chromosome ends from being unnecessarily repaired? It turns out that telomeres aren’t simply naked DNA sequences, but are instead intimately associated with several proteins in a complex known as shelterin. Shelterin proteins help the telomere fold back and associate with itself. This forms a “t-loop” to essentially hide and protect the chromosome end.

F1.large (1)
Telomeric structure and associated proteins. Figure credit: Blackburn et al. 2015.

Perhaps more famously, telomeres also act as a buffer to prevent coding DNA erosion during cell replication. An important consequence of the evolution of linear chromosomes (found in all eukaryotes, from yeast to elephants) is that a few nucleotides are lost with each round of cell division. The DNA replication machinery cannot fully replace the outermost nucleotides, so the DNA strand gets shorter over time. As it is the telomere sequence that caps chromosomes, it is these sequences—rather than the DNA in between—that take the hit.

How are telomeres implicated in the aging process?

Telomere shortening over time is thought contribute to the aging process. Before I describe why this might be, let’s explore a more fundamental idea: what is aging, anyway? Basically, it’s a loss of physiological—or bodily—function. A proposed root case of declining functionality in the body is cellular senescence, or when a cell ceases dividing; a buildup of these cells within a tissue is associated with aging. Telomere shortening is one cause of cellular senescence: when telomeres reach a critically short length, cells cease to divide. This is a mechanism to prevent cells from becoming cancerous. However, there is a tradeoff: a buildup of senescent cells that can no longer induce tumor growth could be driving the aging process.

Telomere length does change with time, but shortening is also influenced by lifestyle and genetics. Some species have “mega-telomeres” (including mice, which are a common model for in vivo telomere length research), which have a different biology than more run-of-the-mill telomeres (as we humans possess). To further complicate matters, some species possess the enzyme telomerase in their body cells. This enzyme replaces lost nucleotides, essentially preserving telomere length over time. However, telomerase isn’t the answer to short telomere’s prayers: 80 to 90% of all cancers are associated with over-active telomerase activity.

The future of telomere research

The initial excitement surrounding telomeres’ discovery forty years ago and the potential for its use as a simple biomarker of aging and disease are still with us today. However, like any biological process, telomere dynamics are much more complicated than we first thought. For instance, while there is overwhelming evidence from the past few decades that telomeres do decline with age across species, it is still unclear if telomere length can accurately predict calendar age. The future of telomere research will continue to evolve away from cell culture work into living systems, and from common laboratory animals to a wider species diversity, including ectotherms (“cold-blooded” animals), plants, and hibernators. Stay tuned for more on telomere dynamics in these “non-traditional” organisms!

IMG_2010
What’s happening in hibernator telomeres? Juvenile arctic ground squirrel hiding in some willows. Photo credit: the author.

Advertisements

New school year, new contributor!

This blog started as a collaborative effort. As we all advanced in our careers and grown families some regular contributors have become irregular contributors, and I have been the primary curator for sometime.

UNTIL NOW!

Sara Wilbur reached out asking to write a guest post. We worked on getting her delightful post out together.

And with the new school year, she’s back for more! She’ll be writing about artic squirrels and telomeres and quirky scientists and life in Alaska.

And I’m thrilled that’ll she’ll be posting on Thursdays. Welcome to the NiB family!

 

In 1974, They Gave The Nobel To Her Supervisor. Now She’s Won A $3 Million Prize

One of the great misconceptions of science is that great discoveries start with a “Eureka!”.

More often than not, great discoveries start instead with a “that’s funny/odd/strange, I wonder what’s going on here”. And that’s what happened to Bell Burnell. She and her graduate supervisor, Antony Hewish, built a radio telescope to observe strange objects in distant galaxies known as quasars. It printed the data as a line (using red ink) across ~100 feet of paper per day. And in pouring over that data, Bell noticed something strange: “an unclassifiable squiggle”

The squiggle was soon identified as pulsars, rapidly spinning neutron stars that emit radiation. Finding them is considered one of the greatest astronomical discoveries of the 20th century. So much so that it won a Nobel Prize… for Bell’s advisor.

However, she gets the last laugh: 50 years after the “unclassified squiggle” in red ink, her discovery has earned her a Special Breakthrough Prize in Fundamental Physics, which comes with a check for $3 million. Dr. Burnell is donating her prize winnings to the U.K.’s Institute of Physics, where they will fund graduate scholarships for people from under-represented groups to study physics.

“I don’t want or need the money myself and it seemed to me that this was perhaps the best use I could put to it,” she told the BBC, adding that she wants to use the money to counter the “unconscious bias” that she says happens in physics research jobs.

The astrophysicist noted there has been an upside to the Nobel snub all those years ago.

“I feel I’ve done very well out of not getting a Nobel prize,” she told the Guardian. “If you get a Nobel prize you have this fantastic week and then nobody gives you anything else. If you don’t get a Nobel prize you get everything that moves. Almost every year there’s been some sort of party because I’ve got another award. That’s much more fun.”

Read the full story here.

gettyimages-583671638-317cdf61059f969215d3e111dccddfe3f4cb8eb0-s800-c85.jpg

Giant Irish Elk Antlers

The antlers of an ancient Irish Elk have been found by a fisherman in Lough Neagh, Co. Tyrone.

The creature was the largest deer that ever lived and has been extinct for thousands of years.

The catch has a span of more than 3 m and is believed to be at least 10,000 years old.

This is just a cool look at a cool extinct animal. So cool.

41020351_1841294482573249_558631058862505984_o.jpg

 

A devestating fire

Any regular reader of this blog will know I love collections.

Which is one of the many MANY reasons I’m devastated about the fire at the National Museum of Brazilian.

In summary: the fire burned for six hours and left behind ashes where there had been dinosaur fossils (including the reconstructed Maxakalisaurus topai), the oldest human remains in the Americas, Luiza, and the audio recording and documents of indigenous languages that are otherwise extinct.

We will never be able to replace these items and the knowledge they contain is irreplaceable. Our collective knowledge is worse off as a result.

And with the devastated feeling of the incalculable loss, we’re starting to take stock of how this could have been prevented.

Funding for one (read about how the museum was underfunded for decades). And another is digitalizing the collection.

But for now, I will remain in morning for the knowledge that has gone up in flames.

lead_720_405.jpg

Speaking of winners: sea stars are rocking this climate change era

Most sea stars look like something that Dr. Seuss made dreamed up. This is especially true of the whimsical feather stars. And while corals and other sea creatures are suffering, feather stars are thriving.

This seems to be due in part to their ability to regenerate their arms. Feather stars have infinite potential to regenerate arms, and in warmer waters they are able to do so faster.

Want to know more about these infinitely limbed winners of the climate change debacle? Read about it here!

feather-star.jpg.653x0_q80_crop-smart.jpg