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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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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Who owns your DNA? Ancestry.com does

“For the price of $99 dollars and a small saliva sample, AncestryDNA customers get an analysis of their genetic ethnicity and a list of potential relatives identified by genetic matching. Ancestry.com, on the other hand, gets free ownership of your genetic information forever. Technically, Ancestry.com will own your DNA even after you’re dead.”

Want to know more? Read about it here.

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The Genetic Oddity that gives Cephalopods their Smarts (All Hail Cthulhu!)

It’s no secret on this blog that I’m fascinated by the intelligence, and recent increase in population size of cephalopods (and by extension their potential to take over our world…).

Octopuses can open jars, squid communicate with their own Morse code and cuttlefish start learning to identify prey when they’re just embryos.

And it turns out that their intellect might be related to the way that they edit their genes. Read about it here.

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The explanation and importance of N50 (or lack there of)

It’s pretty hard to quantify how “good” a genome or transcriptome assembly is. How do you tell you got it right? How complete is it?

One way to determine if it’s a good is N50, which is kind of a confusing concept. It’s not quite the mean, or the median length, but it is well explained in a new post over at the Molecular Ecologist!

And they promise that the importance/misinterpretation of this well used standard for genome/transcriptome assembly will be explained in future posts.

I’m looking forward to the rest of the series!

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Ambitious plans to sequence every organism on earth, seeks funding

“When it comes to genome sequencing, visionaries like to throw around big numbers: There’s the UK Biobank, for example, which promises to decipher the genomes of 500,000 individuals, or Iceland’s effort to study the genomes of its entire human population. Yesterday, at a meeting here organized by the Smithsonian Initiative on Biodiversity Genomics and the Shenzhen, China–based sequencing powerhouse BGI, a small group of researchers upped the ante even more, announcing their intent to, eventually, sequence “all life on Earth.””

Interested? Read more over at Science. 

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