The Doctor Weighs In

Pat and I spent the last two weeks of December hiking, bird watching, snorkeling, river rafting and just having loads of fun in Panama. To all of you who are wondering where to go next-this country is unbelievable in its variety of habitats, climates, geography and diversity of animals.

On the last day, before returning to reality, we took a boat ride on the Chagres river, that feeds its waters to the Panama Canal. The river runs through forest land teeming with animals: howling monkeys, white face Capuchin monkeys, sloths, caymans, birds of infinite variety- and fresh water turtles.

It is the turtles, sliding off a log into the water and remaining submerged for a long time, that got my mind going. How did this ancient species survive the various epochs of ice, heat, drought, floods-and is still alive to share its amazing story with us?

Consider some facts:

• Turtles are some of the longest living animals on earth. In a December 12, 2006 issue of the New York Times Natalie Angier, in an article aptly titled “Slow is Beautiful”, reports that “in March of last year a giant tortoise named Adwaita said to be 250 years old (!) died in a Calcutta zoo.  Adwaita was taken to India by British sailors , according to the records,  during the reign of King George II.”  Another tortoise, this one collected by Darwin in the Galapagos 171 years ago, died in June of last year in an Australian zoo at the relatively young age of 176.
• Fresh water turtles tolerate hypoxia (low oxygen concentration) and even anoxia (complete lack of oxygen) not for minutes, like us mammals, but for months.  This is amazing!
• In hypoxic conditions that last months, the turtles' brain neurons remain intact.  Furthermore, they return to completely normal function when normal levels of oxygen are restored. For comparison, our brain will begin to sustain irreversible damage after a period of about 4-5 minutes of anoxia. As our River Rafting Guide at Rio Chiriqi Viejo in NW Panama told us, "You will only last 4.5 minutes if you are trapped underwater, but it will take us 10 minutes to rescue you."
• The turtle’s heart maintains its function during months of hypoxia. Our heart muscle will start dying within an hour of oxygen deprivation...that is why Emergency Physicians have the mantra "Time is [heart] muscle."
• The internal organs of old turtles (and turtles do give a new meaning to ‘old’) are anatomically and physiologically almost indistinguishable from organs of young turtles.

• How do they do it?

Just think about it: the turtle violates almost every biological rule of longevity. Its size would dictate a significantly shorter life span, more on the order of his cousins the lizard or snake. Its high fecundity or fertility likewise should have shortened its life span.

It also seemingly violates the rules of energy metabolism: we cannot survive longer than a few minutes in hypoxic conditions, and our organs (liver, muscle, brain) would rapidly accumulate lactic acid. Not so the clumsy, slow moving turtle.  They can endure months of hypoxia and do not develop a drop of lactic acid. Inthe classic race between the hare and the turtle. the turtle wins --  wins hand down.

And the answer is…

Like almost everything else in biology-there is no definitive, simple answer. Life is just too complex for simple answers. But we have some knowledge that allows us to form hypotheses.

In previous posts we examined the cellular pathways that break down glucose to provide energy in the form of ATP. For our purposes here it will suffice to remember that glucose begins its breakdown in a process called glycolysis, which does not require oxygen and yields a relatively meager 6 ATP per molecule of glucose.

The end product of glycolysis, pyruvic acid, then enters the mitochondria where, in a process called oxidative phosphorylation it is further broken down to form water and CO 2 as well as 38 ATPs per molecule of glucose.

Obviously, oxidative phosphorylation is much more efficient than glycolysis in producing energy (in the form of ATP molecules); this is due to the use of oxygen in oxidative phosphorylation. But there is an associated penalty-the formation of oxygen free radicals. And like any radicals running loose, they wreak havoc on everything that happens to be in their way. In the cell, they attack proteins that make up the enzymes that are necessary for normal function. They attack the cell membrane, causing leaks of cell content and they attack DNA, causing harmful mutations and cell death.

Hypothesis: turtles do it by sticking with glycolysis .

How could a cell adapt to living on the inefficient pathway of glycolysis? There are basically only two ways. The cell can either accelerate markedly the supply of glucose and thus provide enough energy, albeit inefficiently. This is the adaptation that solid tumor cells have adopted. This is why a tumor, even a small one, can consume a large proportion of the energy intake of a cancer patient.  The other way is to reduce the metabolic rate of the total organism, requiring much less energy, or ATP, so that glycolysis would suffice.

This is indeed how turtles do it. This is why they can survive incredibly long time under water or in anoxic conditions (remember, glycolysis does not use oxygen). And maybe this is why they live so long: they don’t generate those pesky free radicals that are associated with tissue damage and aging.

Fish can do it too?

One might assume that turtles are not unique. After all, fish are submerged in water, a hypoxic environment for prolonged periods of time. The answer, provided by Lutz and Nilsson of Florida Atlantic University in Boca Raton (Respiratory Physiology and Neurobiology, vol.141, pp.285-296, 2004) is astonishing. The carp (Carassius carassius) indeed uses glycolysis for its metabolism, but in the brain, rather than accumulate the normal end product of lactic acid, which would be toxic , the end product is…alcohol! Why couldn’t our metabolism be as much fun?

And isn’t biology amazing?