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Biology

Long-lived sharks challenge ageing theory

Costantini, D., S. Smith, S.S. Killen, J. Nielsen, and J.F. Steffensen. (2017). The Greenland shark: a new challenge for the oxidative stress theory of ageing? Comparative Biochemistry & Physiology A. 203: 227-232. http://dx.doi.org/10.1016/j.cbpa.2016.09.026

Why do we get old?

The Greenland shark has recently be recognized as the longest-lived vertebrate on Earth [Flickr].

The Greenland shark has recently be recognized as the longest-lived vertebrate on Earth [Flickr].

Ageing and longevity has intrigued scientists for decades. As research powerhouses like the United States, European Union, and Japan contend with ageing populations, there’s more interest than ever before in understanding the mechanisms and causes of ageing.

Modern biological theories of ageing fall under two major schools of thought. Both theories have strong support in the research community, and are not necessarily mutually exclusive (both of them could be true) (see this paper for a more detailed overview of both theories).

Theory 1: Ageing as part of the biological program

One theory argues that ageing is a programmed event, and follows a biological timetable similar to that of childhood growth and development. Ageing is a result of time-related changes in hormone patterns, gene expression, and immune system function. This theory would suggest that there is an intrinsic maximum lifespan in all organisms, and that this lifespan would be very difficult, if not impossible, to extend.

Theory 2: Ageing as a consequence of damage

freerads

Click for a great video overview of free radical injury from osmosis.org

The second theory argues that ageing is the result of accumulated damage or errors in normal cellular processes. The general idea is a body is like a car – it works perfectly when it’s first driven off the lot, but slowly falls apart as wear and tear build up. In a living system, faulty interactions between proteins or damage to cellular components accumulate until the body breaks down. Under this theory, if cellular damage can be prevented or reversed, maximum lifespan can be extended, perhaps indefinitely.

How long-lived animals can stay young

A popular experimental design to test to damage theory of ageing (theory 2) is to compare the physiology of animals with different maximum lifespans. For example, we’d expect that long-lived animals would be better than short-lived animals at preventing and/or repairing damage to their cells. Oxidative damage (or oxidative stress) in particular has been associated with ageing for decades (Harman 1956).

Oxidative damage is caused by unstable free radicals (also called reactive oxygen species) interacting with proteins and DNA. This interaction can lead to the deactivation or break down of these important biological molecules. Free radicals are produced in small amounts as a natural by-product of cellular metabolism. Free radical levels can increase during exposure to some environmental stressors like heavy metals, heat, and UV light.

Overview of free radicals (also known as Reactive Oxygen Species, or ROS) and oxidative damage in a cell [Oceanbites, 2015]

Overview of free radicals (also known as Reactive Oxygen Species, or ROS) and oxidative damage in a cell [Oceanbites, 2015]

With the recent discovery of a Greenland shark (Somniosus microcephalus) as the longest living vertebrate (click here for the original study, lifespan of 392 ± 120 years), these sleepy deep-sea sharks have emerged as a potential new model for ageing biology. Little is known about these elusive animals – they are about the size of a great white shark, and inhabit cold, deep waters off the coasts of Canada, Greenland, Iceland (where is it a traditional delicacy), and Scandinavia. This study was the first time anyone tried to relate the lifespan of the Greenland shark to the damage theory of ageing by investigating whether these exceptionally long-lived sharks had exceptional resistance to oxidative damage.

Greenland sharks aren’t oxidant-resistant

Summer view of Tasiilaq, a settlement near Ammassalik Fjord.

Summer view of Tasiilaq, a settlement near Ammassalik Fjord [Wikimedia Commons].

The research team collected red blood cells and skeletal muscle of juvenile sharks caught in Ammassalik Fjord, southeastern Greenland. They measured protein carbonyls (an indicator of oxidative damage) and the activity of glutathione peroxidase, an enzyme that protects against oxidative damage by harmlessly reacting with free radicals. After correcting for differences in body mass, the researchers compared these data to previously published values from a range of amphibians, birds, fish, and mammals.

While protein carbonyls were relatively low in the red blood cells of Greenland sharks (below the 25th percentile), protein carbonyls levels in their muscle were in the middle of a range of all animals tested. Similarly, glutathione peroxidase activity was high (above the 75th percentile) in Greenland shark muscle, but average in red blood cells. Overall, there was no clear pattern of oxidative stress status and lifespan in the range of animals included in the study.

Comparative studies are difficult

Greenland shark, viewed at ~800 m below sea level [NOAA Photo library]

Greenland shark, viewed at ~800 m below sea level [NOAA Photo library]

Investigations like this emphasize how difficult comparative studies can be. For example, the data set used in this study included both juvenile and adult animals. Since juveniles tend to have lower glutathione peroxidase activity than older animals, it makes it difficult to say whether the data collected from the Greenland sharks was representative of their species

Another caveat is that the data set included animals with a variety of lifestyles. The ecology of an animal also influences its oxidative stress system, and this can be independent of its longevity. For example, Greenland sharks live in cold Arctic water and naturally experience very different levels of oxidative stress than tropical fishes and air-breathing mammals and birds.

What do we know about ageing?

While the Greenland shark does not appear to rely on a strong defense against oxidative damage to live for centuries (some Greenland sharks alive today were around when Galieo discovered Jupiter in 1610), other species seem to owe their longevity, at least in part, to preventing cellular damage. Perhaps the Greenland shark has its own quirks and secrets that we have yet to fully appreciate. Clearly, more work needs to be done both on the Greenland shark and on the biology of ageing in general to better understand why we get old.

Brittney G. Borowiec
Brittney is a PhD candidate at McMaster University in Hamilton, ON, Canada, and joined Oceanbites in September 2015. Her research focuses on the physiological mechanisms and evolution of the respiratory and metabolic responses of Fundulus killifish to intermittent (diurnal) patterns of hypoxia.

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