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This week on Nature League, Brit Garner explores aging and lifespan mysteries of life on Earth by breaking down a recent scientific journal article about giant tortoises.

Article citation:

V. Quesada et al.

Giant tortoise genomes provide insights into longevity and age-related disease

Nature Ecology & Evolution, 2018

Article link:
https://www.nature.com/articles/s41559-018-0733-x


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Nature League is a weekly edutainment channel that explores life on Earth and asks questions that inspire us to marvel at all things wild. Join host Brit Garner each week to learn about, connect to, and love the amazing living systems on Earth and the mechanics that drive them.
On Nature League, we spend the third week of each month exploring a current trending article from the peer-reviewed literature.

Scientific information isn’t just for scientists. It’s for everyone!

It just requires a bit of a break down. [CHEERY INTRO MUSIC]. For this month’s De-Natured segment, we’re going to look at an article released in December 2018 in the journal Nature Ecology and Evolution. In this month’s Lesson Plan, we touched on the different processes that organisms undergo in terms of aging.

At the end, we mentioned that this is an open area of research, and that we’re learning new things all the time about how different species live to different ages. In this paper entitled, “Giant tortoise genomes provide insights into longevity and age-related disease”, the researchers investigated the topic of aging by studying the genes of giant tortoises. To do this, the researchers used a method called comparative genomic analysis.

While a gene is just one particular stretch of DNA, an organism’s genome is its entire set of DNA. So in comparative genomic analyses, all of an individual’s DNA is compared with all of another individual’s DNA to find similarities and differences. In medicine, comparative genomic analyses are used to investigate regions of interest that might have to do with something like having a disease vs being healthy.

These methods have been used to find genes and pathways related to metabolism and aging in several long-lived mammals, including the naked mole rat and bowhead whale. Giant tortoises are some of the longest-lived vertebrates on Earth, so you’d think they’d be the main subject of a ton of aging research. However, until this paper, there’d been relatively little genomic analyses done on giant tortoises.

That’s right - it was clearly turtle time. Except these are tortoises, not turtles, so...tortoise time... In their study, the researchers conducted a comparative genomic analysis between one.

Pinta Island tortoise and one Aldabra giant tortoise. The Pinta Island tortoise was a special individual known to many around the world as “Lonesome George”. He was the last remaining member of his species and passed away in 2012 at an estimated age of over 100 years old.

In general, some giant tortoise species can live well into their 200’s! In an early analysis, the team found protein families common to these two species as well as Chinese soft-shell turtles and humans. By comparing the giant tortoises to these outside groups, the researchers could identify genomic differences mostly specific to giant tortoises.

They point out three major processes that seem to have shaped the evolutionary trajectory of the giant tortoises we know today, and one of those processes was metabolism regulation. These protein family results were found during the preliminary analysis, and the team wanted to explore ever further. Instead of just generally exploring the genomes, the team had a few specific hypotheses in mind that they wanted to test.

More specific hypotheses meant more specific regions of the genome, so they also selected a few thousand genes of special interest. These genes were related to several different lines of questioning in the study. Of these, about 500 of the genes they specifically looked at had to do with the molecular control of aging and life span.

And this checks out, because it just so happens that members of this research team were responsible for publishing nine hallmarks of aging back in 2013, some of which we touched upon during our Lesson Plan. While the team found a ton of exciting results spanning topics all the way from tooth development to cancer suppression, in this episode we’ll just be focusing on the results that came from studying this group of aging and life span genes. Of the nine hallmarks of aging they’d previously reported, the team found alterations in the giant tortoise genomes having to do with six of these hallmarks.

Here’s the highlight reel of their discoveries related to these hallmarks of aging in giant tortoises:. Number 1: Genomic instability. Genetic damage accumulates over time due to continuous stress and the breakdown of DNA repair machinery.

In giant tortoises, the team found changes to a key protein used in the DNA repair process. Higher expressions of this protein, NEIL1, are correlated with longer lifespans in both humans and naked mole rats, so now giant tortoises can join the club! Number two: telomere attrition: This is a hallmark of aging we explicitly discussed during this month’s Lesson Plan!

With aging, the end regions of chromosomes, called telomeres, naturally shorten. In giant tortoises, the team found changes to the binding surfaces of a protein called. TERF2 that likely affect the formation and structure of telomeres.

Number three: Loss of proteostasis. Proteostasis describes a balanced state of proteins in cells, and this balance declines with age. In Lonesome George, the team found three copies of a gene related to proteostasis.

Not only that, but this gene has been shown to increase lifespan in fruit flies. This gene was also duplicated in the other giant tortoise species they sequenced, suggesting that maintaining protein balance in cells might be a mechanism for long life in giant tortoises. Number four: Deregulated nutrient sensing: We don’t only lose some sense of taste and smell as we get older, but we actually lose functionality of pathways that recognize and respond to changes in nutrients, like glucose, or sugar.

The team identified modifications in giant tortoise genes involved in glucose metabolism, and these might provide a longevity advantage. Mitochondrial dysfunction: Dysfunction is typically a bad thing for longevity, and mitochondria are really important, so mitochondrial dysfunction makes sense as a hallmark of aging. When mitochondria in our cells lose function, severe disorders can occur, so keeping these cell pieces in working order is essential to long and healthy life.

In tortoises, the research team found several mitochondrial gene mutations that could contribute to longer life, including ones that help with detox and protect from alcohol damage. And no, this didn’t evolve as a result of tortoise bingers, but rather from their diet of fermented fruit. Altered intercellular communication: Cells are in constant communication with one another using several types of signals.

During the aging process, factors like inflammation can cause these signals to break down. In the tortoise genomes they studied, the team found molecular evidence for decreased inflammatory responses, as well as changes to intercellular communication that could increase life span. Overall, this paper presents possible genes and pathways related to the awesomeness that is giant tortoises, including their development, huge size, and amazingly long life spans.

This research adds new data to our understanding of the interactions between genomes and aging. In the words of the article, “A better understanding of the processes that we have studied may help to further elucidate the biology of these species and therefore aid the ongoing efforts to conserve these dwindling lineages.” This article was published in a family of highly prestigious journals, and also made some science news headlines around the globe. Here are some reasons why I think this study is capturing both scientists and citizens.

First of all, it’s about Lonesome George! Now, I know I wasn’t the only one shedding a tear when this majestic man passed away a few years ago. Lonesome George represented the last member of his species, so with his death we lost not only an individual, but an entire evolutionary lineage.

Anything having to do with this tortoise typically finds a way into the mainstream media, and this research paper is no exception. Along these same lines, I think this paper is making the rounds because of something seemingly unrelated to science, and that’s the poetry of the whole thing. It might sound bizarre at first, but just listen to this excerpt from the authors: “Lonesome George—the last representative of C. abingdonii, and a renowned emblem of the plight of endangered species—left a legacy including a story written in his genome whose unveiling has just started.” A story written in his genome??

I mean come on, it’s just... beautiful. And the idea of this single tortoise shedding light on the mysteries of aging is just too delightful to pass over. The last reason I personally think the findings in this paper are capturing scientific and public interest is because in general, the idea of dying isn’t a pleasant one.

At the core of the human experience is knowing that we /aren’t/ immortal, and what that means for the way we live our lives. Any research that gets us closer to living longer inspires something almost cosmic within us. It’s why Ponce de Leon spent all those years searching for the Fountain of Youth and why.

Voldemort née Tom Riddle made all those horcruxes... As with any piece of new research, there are several areas of improvement that exist in this study for follow-up research. My first issue is with the sample size.

Comparative genome analyses can be unbelievably fruitful in terms of what we learn, but without sequencing many different individuals from many different populations from many different species from many different ecosystems...well, it’s hard to get the full picture. That said, the researchers mention that this is a first step into uncharted territories. It’s not that the study is providing an entire treasure map with an X marking the spot...it’s just telling us some possible places to start looking for treasure.

Another point of contention I have with the paper is the mention of using this information to help conserve giant tortoise populations that are in decline. In my opinion, this application is iffy at best. While understanding longevity can certainly help us predict population trends, we’re nowhere close to using this info to edit tortoise genomes and make them immortal.

Teenage Mutant Ninja Giant Tortoises aren’t the way forward in terms of conservation- we’re most likely going to need to focus on things like habitat conservation and population management instead. Basically, how long a species lives won’t help it against the fast paced changes currently facing life on Earth. Thanks for watching this episode of De-Natured here on Nature League.

We’ll be continuing our exploration of metabolism and aging next week, so make sure to check back for our segment called “From A to B”. And to keep going on life on Earth adventures with us, go to youtube.com/natureleague, subscribe, and share.