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.

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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.

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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!

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

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Interested in responsible gene editing? Join the (new) club

You had to see this coming. When we first started discussing the possibility of gene editing, our second thought was “oh shoot, this could get ethically complicated quickly”.

So it’s not surprise that as we continue down this path, many a voice is rising in caution.

Read about some of them here.

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Blue foxes, and what can happen when new-comers infiltrate a small population

Arctic foxes are endangered in Sweden, Norway and Finland, scattered in isolated populations. And a group atop the highest mountain in southern Sweden, Helagsfjället, six white foxes settled in 2000s.

In 2010, a local ranger noticed his foxes had changed color, to “blue”. The influx of new foxes provides an interesting opportunity to study the importance of migrants in small and isolated populations.

And, importantly, it affords me the opportunity to talk about blue foxes, and at the end of the day, that’s also pretty awesome. Read about it here!

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Divided by DNA: The uneasy relationship between archaeology and ancient genomics

Genetics are having a disruptive influence on humans complex past. For example:

Thirty kilometres north of Stonehenge, stands a less-famous group of Neolithic stones. Established around 3600 BC by early farming communities, the West Kennet long barrow is an earthen mound with five chambers, adorned with giant stone slabs. At first, it served as a tomb for some three dozen men, women and children. But people continued to visit for more than 1,000 years, filling the chambers with relics such as pottery and beads that have been interpreted as tributes to ancestors or gods.

The artefacts offer a view of those visitors and their relationship with the wider world. Changes in pottery styles there sometimes echoed distant trends in continental Europe, such as the appearance of bell-shaped beakers — a connection that signals the arrival of new ideas and people in Britain. But many archaeologists think these material shifts meshed into a generally stable culture that continued to follow its traditions for centuries.

But last year, reports started circulating that seemed to challenge this picture of stability. A study1 analysing genome-wide data from 170 ancient Europeans, including 100 associated with Bell Beaker-style artefacts, suggested that the people who had built the barrow and buried their dead there had all but vanished by 2000 BC. The genetic ancestry of Neolithic Britons, according to the study, was almost entirely displaced. Yet somehow the new arrivals carried on with many of the Britons’ traditions. “That didn’t fit for me,” says Carlin, who has been struggling to reconcile his research with the DNA findings.

 

So can genetic studies overturn work done by dozens of researchers over decades? Is the promise of ancient DNA too good to be true, or a whole new window into our ancestors?

Read about the ongoing struggle here.

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Gene editing in farm animals: don’t bet the farm on this pig in a poke

“It is very worrying not only to read about yet another blunder by the industrial farming sector (Pigs in the pink: gene editing is set to revolutionise the farming industry, 17 March) but also that the article didn’t attempt to counterbalance with a different viewpoint. It is well known that healthy, agroecological, farming systems support healthy animals and plants that are then, by and large, resilient to disease. The solution for a sick animal is not to edit genes, because this does not address the cause of the problem and only makes it worse, as the ill health will only find a different way to express itself. In the meantime we are supporting unhealthy farming systems and their associated diseases, and consuming sick pigs.”

This is a fairly good article addressing a problem in the promise of gene editing.

Thoughts?

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Here’s what we really know about transgender genetics—so far

In an awesome piece over at the Genetic Literacy project, Ricki Lewis what is known (and what is largely overblown) about transgender genetics.

TL;DR: It’s a bit too soon to screen for transgender genes, beyond the usual genome wide association studies, and we really should be asking ourselves if, ethically, this is a road we want to go down.

Also, journalist can run with an abstract and things get out of hand quickly. But I’m fairly certain we all already knew that.

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How Not To Talk About Race And Genetics

“In his newly published book Who We Are and How We Got Here, geneticist David Reich engages with the complex and often fraught intersections of genetics with our understandings of human differences — most prominently, race.

He admirably challenges misrepresentations about race and genetics made by the likes of former New York Times science writer Nicholas Wade and Nobel Laureate James Watson. As an eminent scientist, Reich clearly has experience with the genetics side of this relationship. But his skillfulness with ancient and contemporary DNA should not be confused with a mastery of the cultural, political, and biological meanings of human groups.

As a group of 67 scholars from disciplines ranging across the natural sciences, medical and population health sciences, social sciences, law, and humanities, we would like to make it clear that Reich’s understanding of “race” — most recently in a Times column warning that “it is simply no longer possible to ignore average genetic differences among ‘races’” — is seriously flawed.”

Read about it here.

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