Thursday, January 16, 2014

Getting on board with birds: how to duck death

Cory Elowe

Aging is a hot topic, so I hear. I suppose some people would say I’m lucky that I look so young, but unfortunately I’m likely to be carded at bars until I turn gray. Other people aren’t so “lucky” and want to stop the clock and prevent this pesky aging dilemma. Theories have been tossed around for ages, not the least of which was Ponce de León’s 16th-century search for a fountain of youth in Florida of all places. Boy did that backfire. 

Today, gerontology (the study of aging) has shifted largely to the disposable soma theory and “rate-of-living hypothesis”, both of which suggest a planned obsolescence for all living things. A major basis for these theories is the idea that oxidative stress, a seemingly necessary consequence of our reliance on oxygen for metabolic activity, will be, quite literally, the death of us. In 1954, Rebeca Gershman and her colleagues at the University of Rochester noticed that “oxygen poisoning” worked in essentially the same way as radiation poisoning. This likely spawned a generation of couch potatoes, justified by their fear of poisoning themselves with aerobic metabolism.

This is a simplified look at the mechanism: oxygen accepts electrons, especially at the end of the electron transport chain in cellular respiration, but sometimes it fails to accept all of the electrons and you can end up with a rogue, destructive free radical with one unpaired electron. These reactive oxygen species (ROS) can range from mild-mannered to downright viscious. Boasting one unpaired electron, the worst of them attacks the integrity of your lipids, proteins, and DNA like Godzilla in Tokyo (this frequently occurs in the mitochondria, arguably the Tokyo of the cell). This oxidative stress has been used to support the rate-of-living hypothesis, built on the observation that small, reproducing, and aerobically active animals tend to have a short life span because they generate more ROS and suffer more cellular damage (in contrast, metabolism per gram of body weight decreases as animals get bigger and live longer). Hopefully I didn’t lose anyone yet…

Birds are endotherms that appear to foil these theories of aging. Why? Short answer: they are masters of oxygen. The Bar-headed Goose migrates over the Himalayas. People struggle up Mt. Everest with oxygen masks to cope, but this goose soars by, unimpressed with such petty attempts to enter their domain.

Birds know how to use oxygen. Their lungs are specialized for supreme aerobic capacity, utilizing a unidirectional flow of oxygen through a system of air sacs and rigid lungs (parabronchi) that extract oxygen extraordinarily well.

The continuous airflow through rigid lungs allows quick gas exchange with thin-walled capillaries and very little surface tension to overcome, all while maintaining resilience against the powerful mechanical action of beating wings. This efficient respiratory system also requires an absurd amount of fuel—up to 1600 Kcal/kg/day in the 3.5 gram Rufous Hummingbird. What about humans? At most we require 120 Kcal/kg/day as growing babies. This means that birds will use much more oxygen per gram of tissue in their lifetime than most mammals.,
Well, if we were just discussing how bad oxygen is, shouldn’t it be bad to have more of it? Live fast and die young, right? Enter the Rat vs. Pigeon.

Rats and pigeons are roughly the same size, but pigeons can live up to 30 years longer than rats. A study in 1993 showed that alongside this difference in longevity the rats produced about 10 times more hydrogen peroxide (H2O2, a ticking time bomb for becoming a ROS) in their tissues than the pigeons. While controversial, that study is commonly credited as opening the door to the possibility that birds hold the key to aging. Further research suggests that birds indeed tend to produce fewer ROS from Complex I (NADH dehydrogenase) in their mitochondria. During cold-induced increases in metabolic rates Zebra Finches (Taeniopygia guttata) showed no corresponding increase in reactive oxygen species, while similar cold-stress studies have shown increases in oxidative damage in mammals. Furthermore, while birds’ frantic activity may seem like it would generate copious free radicals, it turns out that aerobic exercise may actually serve as a ROS sink by coupling mitochondrial respiration with thioredoxin/peroxiredoxin enzymes, which can defuse huge amounts of  H2O2 before it mutates into something horrific like a hydroxyl radical (HO.), which acts like an older brother coming to destroy your Lego village while you watch helplessly. 

Holmes et al. 2001
Birds show resistance to reactive oxygen in other ways, too. It is well known that blood-glucose levels in bird species consistently rival those of human diabetics. This is because they choose to avoid the heavier, more cumbersome storage of glycogen in favor of using blood as a reservoir for glucose. Despite this, birds appear to accumulate “advanced glycosylation end-products” (AGEs...get it!?) at a slower rate than mammals.  These AGEs are common biomarkers of aging, showing tissue damage such as cross-linking collagens that are often synergistic with free radical damage. Keeping glucose comfortably in the blood could be a way to avoid this treacherous misbehavior in the sensitive environment of the cell. Their hyperglycemia is also accompanied by a depression of insulin signaling, which shifts metabolism to pathways that tend to support longevity.

Lipids are another favorite target of rogue free radicals. Here, again, birds trump mammals. Their cell membranes generally feature hardier phospholipids than humans, whose unsaturated fatty acids suffer higher rates of peroxidation. While this may seem like a fluke, there’s evidence to suggest that the fats from a bird’s diet are carefully selected for incorporation into the cell membrane, potentially due to resilience to oxidative damage.

Antioxidants are a tad more troubling to researchers. They could be a wonderful solution to the aging problem; just pop a pill for your daily dose and keep on keeping on. The popular view of an antioxidant is this: 

A more scientific view is this:

Basically, an antioxidant can donate an electron to the free radical, thus disarming it. With the initial observation that birds fail to align with theories of aging, everyone’s minds went to antioxidants. The result? Not much. It turns out that birds don’t seem to express more, or better, antioxidants. This was surprising considering birds incorporate so many carotenoids—a potent antioxidant—into their feathers for their fantastic displays.
Thus far, the only potential antioxidant in birds that rivals other taxonomic groups is uric acid. Humans and birds share a lack of urate oxidase and therefore must excrete the waste product of protein metabolism. However, uric acid can also clean up free radicals and—guess what?—birds have about three times as much uric acid patrolling their blood stream as humans do! And yes, that amount would be toxic to us. While the importance of uric acid as an antioxidant in birds is largely speculative at this point, its high concentrations are ubiquitous in birds and may represent a vital role for the waste product of their protein consumption.

In all honesty, the jury is still out on aging research. With such a hot topic and so many people searching for the Holy Grail, there's bound to be some speculation and desperation. Nevertheless, birds show an extraordinary capacity for not only efficient use of oxygen but resilience to its two-faced, toxic second nature. There may be no limit to what we can learn from their expertise.


Beamonte-Barrientos, R., and S. Verhulst. 2013. Plasma reactive oxygen metabolites and non-enzymatic antioxidant capacity are not affected by an acute increase of metabolic rate in zebra finches. Journal of Comparative Physiology 183:675–683.

Buttemer, W. A., H. Battam, and A. J. Hulbert. 2008. Fowl play and the price of petrel: long-living Procellariiformes have peroxidation-resistant membrane composition compared with short-living Galliformes. Biology Letters 4: 351–354.

Costantini, D. 2008. Oxidative stress in ecology and evolution: lessons from avian studies. Ecology Letters 11:1238–1251.

Gerschman, R., D. L. Gilbert, S. W. Nye, P. Dwyer, and W. O. Fenn. 1954. Oxygen poisoning and X-irradiation: a mechanism in common. Science 119:623–626.

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Montgomery, M. K., A. J. Hulbert, and W. A. Buttemer. 2011. The long life of birds: the rat-pigeon comparison revisited. PloS One, 6:e24138.

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1 comment:

  1. Wow, definitely didn't know that about birds. I wonder what role birds have and do play as a model organism? Is it an acceptable class of animals? Is it worth it?