Aging Part 2: How People Rust

The more you complain, the longer God lets you live.

     —Old Proverb

This is the middle part of three posts on the science of aging and immortality. Like most middle parts, it's really boring.  If I were you I wouldn’t even waste my time reading it.

Still here?  More fool you.

Back in the early days, about three billion years ago or so, photosynthesis was all the rage.  This is where plant cells would create energy by converting carbon dioxide in the atmosphere into oxygen.  Oxygen, previously  trace element, started to accumulate up to its present concentration of just under 20%.  So the theory goes anyway.

Now most people get a nice feeling when they think about oxygen, probably in no small part due to the fact that they'd be dead in a few minutes without it.  But oxygen is actually an extremely corrosive substance.  Fire, for example, is simply a runaway oxidation reaction (organic carbon à carbon dioxide).  Rust—estimated to cost the economy US$2.2 trillion or 3% of the global GDP—is also oxidation.  Spoiled food—yup, oxygen.

Vigorous oxidation reaction.

 Eukaryotes (remember, cells with a nucleus are called eukaryotes; and cells without, like bacteria, are prokaryotes) didn't much care for this corrosive substance accumulating in the atmosphere.  So they made a deal with some little bacteria.  The bacteria were like, "Hey dude, let me  live here in your big cozy cell and I'll deal with that oxygen problem you got,  plus I'll pay rent in energy."  And the eukaryote cell was like "Awesome!  Stay as long as you like."  And the bacteria did. For the last few billion years.

Those bacteria, called mitochondria, are still there, in every single cell of the trillions of cells in your body. Not just human bodies, but every cell in a dog's body and every cell in every flea that lives on the dog.  They are not part of "you"; they contain their own DNA.  (Actually, because mitochondria DNA passes on to the child from the mother only, apparently we can trace every human alive back to one woman—the Mitochondrial Eve—who lived about 200,000 years ago.  But that's a blog post for another day.)

The mitochondria are the furnaces of the cell, burning (oxidizing) food to create energy.  But like all furnaces, there's issue with leakage and problems with stuff that doesn’t get completely burned.  Sometimes they form highly reactive chemical intermediaries called free radicals, which, like political radicals, are unstable and wander about basically looking to start trouble.  These radicals can mutate the DNA either the mitochondria or, uncommonly, of the parent cell itself ("your" DNA).  It's believed the DNA mutations caused by this (called oxidative stress) contribute to cell senescence (old age).  In a way, we rust.

Problem is, it doesn't explain why dogs, who basically share 80% of our DNA, burn through seven years for every one we do.  Or why a flea, which still has about 60% shared DNA with humans (scary, isn't it?) die within weeks.  It doesn't make much sense, given the similar cell mechanics and biology, that humans live a hundred times longer than a flea, or thirty times longer than mice, or seven times as long as a dog.  With such similar cell genetic characteristics, why don’t all species have similar wear and tear and therefore similar life spans?

Nobody really knows why as far as I can tell.  A prevailing theory is that, because humans reproduce when we are relatively old compared to, say, fruit flies, and because we spend a long time rearing our young, our cells have developed more complicated mechanisms to prevent or repair cell mutations caused by oxidative stress, ultraviolet light, radiation, viruses and just-plain intracellular cock-ups where one of the proteins screwed up on the Friday afternoon shift and created a mutant. 

Evolution would breed out mutations that kill us before we reproduce (that gene line would abruptly end), but mutations that kill us after we reproduce will not be "bred out" by evolution?  Let's say you're a car.  It's not like your genes are taking it in for preventive maintenance to get a good resale value.  No, if you're a car, your genes are like "Get this thing to Vegas, then who gives a rat's ass what happens to it."

Your body, according to your genes.

When you are young, your cells are good at dealing with mutations.  One protein, for example, p53, is a real Horatius at the Bridge against mutant-causing agents.  If it detects damage to the DNA it slows down the cell cycle until it can be repaired.  If the damage to the DNA is severe, it even initiates cell suicide.  Later in life, as cell mutations accumulate over time, and poor old p53 is a lot busier and starts to build up in the cell, inhibiting the cell cycle and shunting the cell to senescence, or old age.

p53 protein (white), a guardian of the cell, attached to DNA (green and blue)

So the courageous "Thou Shall Not Pass!" p53 protein and others like it, that protect the DNA early on eventually lead to cell senescence and death.  So the theory goes, anyway.

Interestingly, there is one way to lengthen life span significantly—at last in lab animals.  Calorific restriction.  Animals that get all the nutrition they need, but have their calorie intake reduced by about 40% live 50 to 80% longer than normal, and live active lives.  Calorie restricted primates have a slightly lower core temperature than others, leading to speculation that a less active metabolism slows down the bodies aging mechanisms.  So if you eat nothing but a little bit of green beans and tofu every day, you may indeed live significantly longer.  Even if you don't, it'll certainly seem that way.

So, cell senescence may be due to an intracellular "autoimmune response," if you will, as a result of DNA mutations that naturally accumulate over time.  Considering that your average DNA gets hit by mutagens tens of thousands times a day, and multiply that by a hundred trillion cells or so in your body, you can see how they'd add up.  But eventually the mechanism designed to repair such damage shunts the cell to a senescent state.  What if there were a way to fool the cell into thinking it was still young?  What if you could make the cell immortal?

Next up:  The exciting finale—Immortality and Cancer