Aging Theories


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Everyone gets old and everyone dies. But why? The question is very fundamental and as difficult to answer as why we are alive.

Aging and death seems somehow inherent to human cells, or at least those cells within our environment. Normal human cells die out after dividing a number of times, even when kept alive in ideal laboratory nutrient conditions. But some cancer cells and virus-infected cells can be "immortal" and divide indefinitely. What makes human cells inherently full of death? Is it programmed? Or if we can cure all known human diseases, will humans live indefinitely?

Or is aging a disease itself? There are diseases that cause premature aging. Perhaps normal aging is a disease too. And if so, can it be cured or delayed?

An interesting question is whether people would die if they had a "perfect" environment. Is the human body capable of immortality given the right environment? If a human could get the ideal atmosphere, diet, light, and other external factors, would they live forever? Or is there a programmed age limit for cells no matter what environment humans live in?

If there is a preset limit for human lifespan, it is probably of the order of around 120 years. And quite possibly, some people's limit might be slightly different. After all, animal lifespans are not the same as humans.

There is much circumstantial evidence that aging is well-defined and even programmatic. Humans age in similar ways and on a similar schedule. After all, we start our fetal and childhood life growing to a very clear schedule, why should it be different for the end of life?

The same is true of animals and there is much evidence of regularity of aging in the animal world. Like humans, animals seem to have a regular life-span that is similar for animals of the same species, though obviously different across species. Domesticated animals do live longer on average than wild animals, as they avoid many risks, but domesticated animals don't live significantly longer than the oldest of the wild animals of the same species. Similarly, civilized health care makes more people live closer to the lifespan limits, but it doesn't make any people live significantly beyond the apparent limits.

In my opinion, death like growth is probably programmed. But if so, why so? Religious answers are numerous. Evolutionary theories state that the death of the old helps the gene pool diversify and so confers evoluationary advantages. All such theories are interesting, but inherently unprovable and of little value in detailed analysis.

Theories of Aging

There are numerous different theories in the literature on aging research. They can largely be categorized into the following types of theories:

  • Statistical theories: cumulative random cell damage over time
  • Programmed cell death theories (called "apoptosis")
  • High-level program control theories

At the heart of the debate is really a critical issue about "code" and whether a cell acts alone or as part of an intelligent system. Is a cell a dumb automaton reacting purely in response to the stimuli of its surrounding environment. Or is the cell itself a very intelligent creature executing its own program to handle its environment.

These categories are not mutually exclusive theories. For example, even if a high-level control program decides when cells should die, it might also kill damaged cells earlier, and the method of death might be programmed cell death. So the theories are very interlinked.

Cumulative Random Cell Damage Aging Theories

There are several aging theories that are statistical or stochastic. The idea is that there is no built-in aging program, and that aging occurs as a statistical process. If we were just lucky enough to avoid the bad things in the world, we would live much longer.

The basis of these theories is that all humans are subjected to numerous cellular incidents that damage the cells. These accumulate over a lifetime and gradually overwhelm the body, causing aging and the cellular decline that eventually leads to death. Some of the possible theories of random cell damage include free radicals, DNA mutations, or the gradual build-up of the body's own waste poisons.

While this theory is interesting and well advanced, my opinion is against it. I find it difficult to believe that the start of human life is so programmed, but the death is random is statistical. I do not consider that I have disproved this theory, but only that I do not prefer it.

Programmed Cell Death Apoptosis Aging Theories

All cells have a feature known as "programmed cell death" or "apoptosis". It is really a form of cell suicide. In fact, it is a very ordered shutdown of the cell through gradual shrinkage and eventual dispersion. It is much less messy than the abrupt death of a cell through cellular injury. The steps involved in apoptosis have been immensely studied in recent years and seem very regular.

Theories of aging that use apoptosis seem to imply that as people age, more of their cells start to decide to suicide. One of the main theories uses the Hayflick phenomenon. According to this theory, cells divide until they cannot further, whereupon this is recognized and triggers the apoptosis sequence.

High-Level Control Aging Theories

This type of theory has the idea of a kind of master control or master clock. Realistically, there are two main ways that this theory of aging could work:

  • Cells act independently: each cell somehow knows the age of the person, and starts running the later stages of its DNA program. Thus a cell ages on its own.
  • System control: the entire body somehow keeps its own clock, and as we age, starting off the end-stage sequences using whatever major cells, organs or enzymes are required. In this theory, a cell does not age unless it gets the aging signals from the body's master program.

This theory of aging is almost identical to the question of growth and life. How do cells know when to grow and what to grow in order to create a new fetus. In my view, aging is exactly the same process, just a few years later. I give no real justification for this view other than this would make the human program divinely elegant.

Both variants of the overall control theory of aging share a common element: the program that controls when various aging features are activated are stored in genes in the DNA code. Whether it is each cell making age-related genetic decisions independently, or the whole organism making decisions centrally somehow, both theories find the code in the DNA. Therefore, the key to aging is the master genes in the DNA. And with no real surprise, we note that similar master genes are responsible for cell differentiation and timing of gene activation during early growth. Aging is just another stage of life.

Evidence for programmed aging: One of the main issues is early aging diseases such as progeria, though the aging is not exactly identical in this disease to normal aging. A classic example of an apparently programmed death is salmon dying off immediately after spawning, though admittedly this is not an aging issue as such.

Facts and Theories about Aging

Everyone dies is a fact. Whereas there are genetic diseases of premature aging, there are no diseases causing immortality. There are many people living past 100 today but none living to 200. However, there is much variation in lifespan across individuals from both genetic and environmental effects.

Hayflick phenomenon: cells have a finite doubling potential, and become unable to replicate after they have done so a number of times. Some cancer and virus cells are not restricted, seemingly with an infinite doubling potential, and are thus immortal cell lines. One reason for the Hayflict phenomenon may be that chromosome telomeres become reduced in length with every cell division, and eventually become too short to allow further division. When telomeres are too short, the p53 gene notes this and causes the cell to die.

Premature Aging Diseases

There are several diseases that cause rapid aging. In reality, they do not actually cause normal aging sped up, but create distinct features that include some aging features. Unfortunately, all usually cause early death.

  • Classic progeria (Hutchinson-Gilford syndrome): probably autosomal recessive, obvious early, death in the teens. See also progeria.
  • Werner's syndrome: autosomal recessive, occurs later, patients usually survive to middle age.
  • Ataxia-telangiectsia - the "fragile chromosome syndrome"
  • Others: Leprechaunism (an insulin receptor mutation disease), Rothmund's syndrome (mental retardation, skin pigment blotches, osteoporosis, and cataracts) Progeroid syndrome (early signs but long life).

None of these diseases are exactly like aging. They seem to speed up one or several aspects of aging, but none are exactly the same as watching normal aging at a faster pace. This would seem to indicate there are a great many processes involved in normal aging, and these diseases may affect only some of them. The idea of multiple aging processes is also consist with the fact that there are no known immortality or fountain of youth diseases: such diseases would require mutation in numerous aging processes, and while perhaps not impossible, would be extremely unlikely.

Diseases Related to Aging

Older people get more diseases. This is true of cancers, heart disease, stroke, atherosclerosis, prostate disease, osteoporosis, Alzheimer's disease, and numerous others.

There is much discussion about whether diseases are related to aging itself, or just become more common the longer we live and the weaker we get. The question is whether age will eventually cause a disease versus just raise its prevalence.

For example, it seems likely that everyone who lives long enough will suffer from common hearing loss, but might not necessarily get cancer, though it would become more likely. The categorization goes something like:

Older people get fewer common colds because they have become immune over their lifetime to numerous viruses. But the elderly are very vulnerable to cold and flu viruses against which they are not immune.

References

  • AGING, Ed Friedlander, M.D., Pathologist, http://www.pathguy.com/lectures/aging.htm.

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