Look up, look outside. Every organism you can see, and many of the ones you cannot, are equipped with infinitesimally small “clocks” that track the age of each and every cell. These clocks are known as telomeres, which are repetitive DNA sequences that protect the ends of chromosomes — the structures that organize our genes — from degradation. You can think of them as the plastic or metal aglets that cover the ends of your shoelaces and protect them from fraying. If your chromosomes were shoelaces, the aglets would be the telomeres.

Credit: Hesed Padilla-Nash and Thomas Ried, National Cancer Institute, National Institutes of Health.

Across all eukaryotes, or organisms with a membrane-bound nucleus (from yeast to ground squirrels to humans), the telomere sequence is identical: TTAGGG, repeated thousands of times. As telomeres within a cell shorten over time due to normal cell division and metabolic stress, molecular pathways are activated that drive the cell to cease division — a state known as senescence — or to die. A buildup of senescent cells within an organism is linked with aging and many types of degenerative diseases.

To keep telomeres intact in our stem cells and germ-line cells, an enzyme known as telomerase can be recruited to telomeres to replace lost nucleotides. Although useful in these progenitor cells, overactive telomerase in our somatic (body) cells poses a problem: 50–100% of tumors (depending on tissue) have detectable telomerase activity. Oddly enough, both short telomeres (which cause senescent cell build-up) and long telomeres (kept lengthy by inappropriate telomerase activity) are implicated in cancer development.

TTAGGG

Since their discovery in the late 1970s by Elizabeth Blackburn and Joseph Gall, telomeres have fascinated geneticists and, increasingly, the public. Researchers are curious about how telomere length changes over time, implications of degraded telomeres for cancer initiation and progression, and telomere length in the face of physiological challenges such as oxidative stress. Scientists and broader audiences alike are interested in how telomere length could predict longevity and how lifestyle might impact their integrity.

Unfortunately, there doesn’t seem to be a simple, direct relationship between telomere length and how old an organism is. In general, telomeres do shorten with age in most taxa. However, telomere lengths of two age-matched individuals of the same species can be highly variable and differ across tissues based on genetics, varying cell division rates, level of telomere-specific DNA damage, or differences in how cells respond to telomere shortening. For instance, your father, at age 70, could have longer telomeres in some tissues than you, at age 30, depending on the factors listed above.

Elucidating the mechanisms that affect telomere shortening, especially through in vivo studies on a broad range of model organisms, helps us understand this dynamic and complex process. Such work may one day illuminate a robust connection between telomere length and longevity.

One factor between telomere length and longevity might be metabolism…

I am a graduate student at the University of Alaska Fairbanks. My work focuses on telomere length dynamics in the most extreme mammalian hibernator on Earth, the arctic ground squirrel (Urocitellus parryii). This animal hibernates and survives through sub-freezing temperatures for more than half of every year!

Arctic Ground Squirrel. Credit: NPS Photo/Kent Miller.

I found inspiration for my research at the 2016 International Hibernation Symposium in Las Vegas. Physiologist Thomas Ruf from the University of Veterinary Medicine in Vienna shared new research on telomere dynamics in a temperate hibernator, the edible dormouse (Glis glis). With DNA extracted from cheek cells at pre- and post-hibernation, the Viennese researchers found that telomere length decreased over one year and that this effect was best explained by number of arousals (in other words, the dormice that aroused more during hibernation had greater telomere shortening). Through a fortunate series of events, I was able to travel to Vienna in 2017 to work with Ruf and colleagues in developing my own assay for measuring telomere length in hibernating arctic ground squirrels.

Surviving the arctic winter

Hibernation is a state of prolonged dormancy, represented most famously by the bear. Ground squirrels are also exceptional hibernators, retreating to their burrows for 7–8 months out of the year and living off of only fat reserves. [Editor’s note: Kind of like you when you are fasting through the night! Only much more extreme…] Although outside appearances suggest that ground squirrels are completely inactive, their underlying physiology is remarkably dynamic.

Hibernation in the arctic ground squirrel can be divided into two alternating phases: torpor, or a profoundly quiet metabolic state with very low heart rate and internal temperature, and arousal, a brief yet dramatic return to active-season-level metabolism. Arctic ground squirrels experience 12–15 arousals throughout each hibernation season yet spend the majority of their time at body temperatures as low as -2.9°C (26.8°F).

Arctic ground squirrel core body temperature (solid line) and nearby soil temperature (dashed line) over one winter near Toolik Lake in northern Alaska. Image credit: Cory Williams, University of Alaska Fairbanks.

Arctic ground squirrels have large pockets of brown adipose tissue (BAT) stored around their heart and brainstem. When a squirrel begins to arouse (side note: no one is quite sure why hibernators periodically rewarm, or what triggers this. Current research at the University of Alaska Fairbanks is trying to uncover a piece of that mystery!), it first warms through non-shivering thermogenesis, or internal heat production, which occurs in BAT.

Mitochondria — the organelles that provide cellular energy in the form of adenosine triphosphate, or ATP — are found in abundance in BAT. Mitochondria in BAT go into overdrive during an arousal, producing heat in addition to ATP. Once the animal reaches a certain temperature it begins to shiver, creating even more internal heat. Finally, the animal reaches “normal” body temperature, stays there for a few hours, and then slowly lowers its metabolism and body temperature again to prepare for the next torpor bout.