The Entropy Theory

Surprisingly, at what we believe to be the dawn of immortality, mankind currently finds itself without a unified theory of aging. And although the telomere theory is rapidly rising in the spotlight, the ‘entropy’ theory of aging, in one of its various forms, is still probably more popular among scientists and the general population alike. The entropy theory of aging is basically that we age from wear-and-tear. Or more precisely, that the corrosive effect of our own metabolism, coupled with a host of other outside assaults, often in the form of free radical damage, causes our bodies to wear down on multiple levels from the cellular to the macroscopic, with glycation, Mitochondrial and Nuclear DNA damage being at the forefront in various versions of this theory. Our bodies try to repair this damage, but to the degree to which the repair mechanisms are imperfect or unable to keep up with the damage, we age. In short, like an old house or car, we unravel.

Entropy's Conundrum - Immortal Cell Lines

This seems reasonable enough, but when we stop to consider the fact that cell lines that maintain telomere lengths do not suffer from any of the 'wear-and-tear' damage listed above, the theory begins to fray at the edges. This includes embyonic stem cells, germ cells, and all immortal single-celled organisms, which are almost all single-celled organisms. With respect to DNA damage in particular, this is because of the simple fact that allowing that kind of damage in those cells types was simply not a luxury evolution could allow life to entertain. If germ cells accumulated this sort of DNA damage across divisions, every species would quickly be driven into the ground as that damage accumlated in the germlines that spawned successive generations. The same is true for immortal single-celled organisms. Life requires that the core cells that represent its line maintain near perfect fidelity, otherwise life simply cannot work, and the repair and renewal mechanisms of the cell have, billions of years ago, risen to this challenge because they had to. And DNA damage is really the only cellular damage that matters because any other damage is not carried on across cell divisions. The proteins that make up the new cell are coded, from 'scratch', from the newly copied strand of DNA. As a consequence these cells are indistinguishable from those that came before them. Together the 'immortal' cells actually represent the majority of cells on Earth, and the backdrop against which mortal multicellular life evolved. The somatic cells in the bodies of various complex organisms, on the other hand, whose telemores do erode, are unique in the world in that they accumulate damage across cell divisions.

Nature has a precise plan at the cellular level. Where it needs immortality, it maintains perfect telomere length and the result is pristine immortal cells impervious to wear-and-tear. Where it needs high proliferative capacity, but not quite immortality, as in adult stem cells, it expresses telomerase, but not enough to halt telomere erosion over a lifetime. And where it needs neither, it lets telomere shortening run its course. The question is: What is nature's plan for us? What does it need from us and what rights and powers of life have we been granted as a result?

Other Problems with the Entropy Theory

Also, consider these problems with the entropy theory:

• Every cell in your body is actually part of an immortal cell line going back to the dawn of life, and they have suffered no damage from that 4 billion year trip. This is possible because until now that trip was taken entirely in the immortal cell compartment as germ and embryonic stem cells, as the journey in that line from single egg to an egg in a fetal girl's (ie your mother's, grandmother's, etc) ovaries was repeated. Why now, in the final 70 years of this journey, will wear-and-tear get the best of most of your body's cells?
• It fails to explain Progeric syndromes - diseases of accelerated aging.
• It fails to explain the wide range of lifespans in the Earth's species and how the ravages of wear-and-tear have already progressed throughout the body of a 2 year old mouse, but have almost left a 28 year-old human relatively untouched.
• It fails to explain how some animals - the Lobster, Rainbow Trout, certain species of Turtle, Sharks, Rays, Alligators, and the Bristlecone Pine age either not at all or undetectably.
• It underestimates the body's capacity for renewal and repair. It views aging in animals as similar to aging in a house, where entropy gradually gets the best of it. But an animal is actually like a house whose every molecule is actively involved in the house's maintainance and where entire structures are constantly broken down and rebuilt on many levels. All of the systems mentioned above are in fact maintained perfectly well for three decades as a human, but begin to breakdown inexplicably after that. Aging is in our opinion, not the entropy inflicted on the house, but the gradual failure - or more specifically the intentional abandonment - of the repair mechanisms that maintain these systems.
• It fails to explain why the world's mortal and immortal species appear to be divided precisely along the lines of those whose telomeres erode and those that do not.
• Above all, it looks for the 'efficient' cause of aging and not the 'teleological' cause. That is, it does not think to ask the question: Does aging have a purpose? Nature has precise control over all biologoical functions in the natural world and they all exist for a reason. But aging, as universal as it is, is assumed to be a lone exception to this, and this assumption is further assumed to be so self-evident that it need not be defended, argued or really even pointed out.

Nature Abandonment Theory

There are some popular variants of the Entropy Theory that begin to introduce the concept of the individual's interests taking a back seat to those of the species, which is the right direction. But they don't go far enough. The Nature Abandonment Theory, for example, states that nature doesn't care about us after our fertile years, because at that point we've already handed down our genes and will not be handing down any more. If a gene exists which disposes us to a heart attack at age 50, as opposed to 12, that gene will most likely get handed down, and in such a way the genes that abandon us in old age are passed along, and that this is essentially what aging is. We're getting warmer with this theory, but it still has problems:

• In response to the question 'Why are our lifespans limited the way they are?', to answer by first assuming a fertile life with a finite window of a particular length begs the question.
• It is predicated on some mechanism by which the genes change effect, or expression, over time, for a gene to be able to suddenly cause damage late in life. But this in a nutshell presupposes a fundamental aging mechanism in order to explain it. In fact there is such a mechanism - it is called the telomere position effect, which is sufficient in itself to explain aging.

In sum, Nature Abandonment assumes a finite life and relies on a fundamental aging mechanism in order to explain those very things and still offers no explanation of a downward pressure on age.

Extrinsic Causes of Death

Certain animals live longer than others. But why don't they all live for hundreds, or thousands of years? What is the downward selection pressure on age putting a cap on this? It has been understood for a while that the likelihood of death by extrinsic causes (i.e., predation) is controlling the ages of various species. Species that are likely to get picked off within a few years anyway, such as mice, have lifespans that don't go much beyond that. On the other end of the spectrum we have animals like certain seabirds and Humans which have few predators and are relatively long-lived. Interestingly, the immortal species (Lobsters, Rainbow Trout, certain species of Sharks, Rays, Turtles) score pretty low on the extrinsic likelihood of death scale as well. The explanation for the mouse's shorter life is, under a corollary of the Nature Abandonment Theory, that a mouse isn't going to get much procreation payback for living for 10 years, since it is likely to get eaten before then anyway, so evolution does not select for for a longer-lived trait.

The lifespans of various species do seem to be pretty neatly organized along this axis. First and foremost, this should tell us something though - that nature is in the driver's seat of longevity. Nature is not a helpless victim of entropy, but can, on the contrary, easily increase the lifespan of a species by 150 times (Shrew versus Giant Tortoise) if evolutionary conditions give it motivation for doing so. This should really alone put any wear-and-tear theories of aging to rest, and should also tell us that any theories of aging without a 'teleological' cause component should be questioned. In other words, there will always be wear-and-tear. The question of aging is: When, why and how does nature abandon its repair and renewal mechanisms that combat it?

As a theory to explain the underlying reason for the variance in different species' lifespans, the Extrinsic Causes of Death theory succeeds. But it has been used for more than that and taken too far. It has, in a way very closely related to the Nature Abandonment Theory, been used to explain aging per se, by positing that aging is simply the result of thousands of time-bomb genes in our DNA that have been allowed to slip in undetected because our ancestors essentially died of other causes first, and that therefore evolution did not have the opportunity or motivation to weed them out.

But we have a question for those who follow this theory of aging:

If you really were to put an immortal mouse into the wild, what are the true chances that it would die of extrinsic causes before that species' natural lifespan, say two years? Is it really over 99.9%? Because if it's not, the extrinsic causes/ nature abandonment death theory is no good. The slightest edge in the game of procreation and survival is borne out in the game of evolution. Has anyone ever observed mice, or any other species in the wild, to determine conculsively that they die overwhelmingly of extrinsic causes before their natural lifespan is up? There is not really any evidence out there demonstrating that this is the case. And if there were, it should be rejected as defense of the nature abandonment theory, because it would be logically bound to the conclusion that no animals in the wild die of old age.

In a nutshell, the extrinsic causes theory of aging fails to offer a source of downward selection pressure on age needed to explain aging and death per se. Without it, only a positive procreation payback, however small, could come from a long-lived mouse and there would be nothing stopping a continual age increase of all animals as evolution progressed.

The downward selection pressure, we believe, comes from supraindividual evolutionary forces - i.e., species vs. species competition, as we will explain later. This can be seen as balancing against the forces of individual evolution which push only upwards, where the compromise between the two forces is the life span of the species. But a better perspective, really, is to see the life span of the individual as a trait of the species, in precisely the same way that the lifespan of a red blood cell is a trait and function of the body and not of the cell. Quick or slow turnover is a survival strategy for the species, meant to match environments where those species are at the bottom or top of the food chain, respectively. Quick turnover allows the species not to be hunted to extinction, for species where there is a danger of that. Slower turnover, where that luxury exists, allows the species to develop larger and more complex animals that can occupy and maintain more complex and demanding niches.