“Rule-breakers” Aid in Quest for Mysterious Fountain of Youth

The National Evolutionary Synthesis Center (NESCent) is currently holding their annual blog contest. The winner gets cash, money to put towards attending SciOnline2014, a science communication conference, held in Raleigh, NC. This post serves as my entry, in all its hopeful, optimistic glory. Wish me luck!

With so many products on the market claiming success in reining in the ever-elusive fountain of youth, it’s no wonder society (a certain blogger included) is willing to spend exorbitant amounts of dough on these products. Is it possible that said fountain of youth might be, instead, hidden among our genetic code?

A brand-spanking new study reveals some promising results to suggest just that. Using the power of exceptions to the norm (or, as I like to call them, “rule-breakers”), coupled with sophisticated molecular evolutionary analysis, this study delves deeper into the molecular underpinnings associated with aging and longevity in mammals.

The three rule-breakers in question are none other than the naked mole rat, the little brown bat, and, of course, humans (We can never seem to follow the rules, can we?).

Behold. The amazing little brown bat!

Behold. The amazing little brown bat! (Photo credit: USFWS. Used with permission under the Creative Commons License)

So, how does this seemingly hodge-podge assortment of species get lumped into my arbitrary and newly-defined category of “rule-breakers”? Well, generally among mammals, there is an apparent correlation between body size and life span, with larger mammals tending to live longer; however, this is not the case in the three aforementioned species. They are severely out of line with what should be expected based upon body size alone. The 10-gram little brown bat most drastically demonstrates this by boasting a maximum lifespan of 34 years!

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Body weight is plotted against longevity to show a strong correlation between body size and life span. The bigger you are the longer you should live! Notice the “rule-breakers” as obvious outliers. (Figure modified from Morgan et al., 2013).

In an article published last month in the journal BMC Evolutionary Biology, Morgan and colleagues used these exceptions to the norm to their advantage by comparing the three rule-breaking species with 26 other rule-following species to look for possible changes in telomere-associated genes that might explain why these species can live so long, despite their small body size.

Lets’ learn. Telomeres are a repeating sequence of the genetic code that cap the ends of mammalian chromosomes. It is well established that telomeres are very important for maintaining chromosomal integrity, and thus, cell vivaciousness (hint: anti-aging properties). I like to think of telomere function as analogous to the bottomless chips and salsa you find at Chili’s.

You will never see the bottom of this bowl!

You will never see the bottom of this bowl…or will you?

Each time a cell divides, the chromosomes gets truncated at the ends. This is bad. The ends are imperative for carrying genetic information that must be replicated, and passed on during cell division. The telomeres, acting as the chromosome’s savior, make the ultimate sacrifice by allowing themselves to be chopped off in lieu of the important genetic material. And here is where our hypothetical chips and salsa come in. The enzyme telomerase (think: uber-attentive Chili’s server) is constantly refilling the telomere stock that gets depleted in each cell cycle. See? Bottomless telomeres…I mean chips and salsa.

But eventually our fictional Chili’s server gets bored and stops refilling his or her patron’s chips (I guess they’re not really bottomless after all). The patrons eventually run out of chips. Sad.

The same happens with telomeres, as telomerase will eventually “get bored” and stop renewing them. This leads the telomeres to shorten to the point of hindering cell division, along with a host of other detrimental effects. This lack of cell division manifests as the outward signs we call aging.

The authors of this ground-breaking study decided that telomere-associated genes, the suite of genes that regulate telomere function, might be a good place to search deep within the recesses of the genome to discover if there were any advantageous changes in those genes in our three long-lived species, when compared to species that cannot claim to have mastered the secret to anti-aging. What genetic surprises are they holding?

The authors arrived at the astonishing conclusion that there are, in fact, a large number of genes that do show advantageous changes in telomere-associated genes when comparing rule-breakers vs. the rule-followers. Of noted importance was the fact that the genes that display these changes are different between bats, naked mole rats, and humans, suggesting that long-lived species may have evolved different ways to combat aging. And to that I say, “I guess there really is more than one way to skin a cat!” The authors propose that these differences might be due to disparities in timing of reproduction and/or survival strategies.

Adorable, aren't they? (Photo credit: Smithsonian National Zoo. Used with permission under the Creative Commons License.)

Adorable, aren’t they? (Photo credit: Smithsonian National Zoo. Used with permission under the Creative Commons License.)

For example, in naked mole rats, older females produce more offspring than young females which is contrary the reproductive strategies of little brown bats and humans.

This elegant study offers a first-glimpse into how genomes might hold the secret to finding the elusive fountain of youth. As the old adage goes, “Rules were made to be broken”. I guess this might be true after all. Alright, I’m off to rob a bank!

Reference: Morgan CC, McCartney AM, Donoghue MTA, Loughran NB, Spillane C, Teeling EC, and O’Connell MJ. Molecular adaptations of telomere associated genes in mammals. BMC Evolutionary Biology 13:251. 2013.

UPDATE: The results for the blogging contest are in. I did not take home the top prize; however, I came in first runner-up! As a novice science writer, I couldn’t be more pleased. Thanks, NESCent, for the awesome opportunity to hone my skills!

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