Monday, April 27, 2009

Physical Immortality

In 1953, Dr.Watson and Crick discovered the nature of the double-helix of DNA. This ushered in a new era in medicine-that of molecular biology and eventually genetic engineering. As we learn the secrets of the cell and unravel the genetic code, we find that aging is primarily caused by a loss of genetic information. A series of intracellular instructions and malfunctions kill us off. Soon, we may learn how to control the aging process by manipulating our DNA, and perhaps forestall death. The devil is in the details.

Humans fear disease, decay, and death. Our biology programs this fear into us, for survival purposes. The great unknown darkness that awaits us all is so terrible,we invent religion to cope. A culture that accepts death is created and reinforced by various thinkers...Aristotle declared that only the heavens were changeless and eternal, while the lower regions were subject to decay. His view was incorporated into Christendom through the medieval theologian Aquinas. Doctor Galen and the Muslim Avicenna promulgated the same reasoning-humans must be content with their mortality. Hopefully soon, we as a civilization will shake off this bugbear and develop ways to extend life by several decades. This will allow those of us who are relatively young and healthy right now to live long enough to benefit from future immortality research.

Why do we age?

In the 1950's Sir Peter Medawar and Dr. George Williams devised the evolutionary theory of aging: very primitive organisms reproduce asexually-through a process known as fission. These creatures are immortal-they pass on an exact copy of themselves every time they reproduce or divide. When higher organisms invented sexual reproduction, death was devised.
Since natural selection edits out or eliminates organisms that fail to adapt to hostile environments, the purpose of sex is to shuffle the genes, to create genetic variety in an effort to insure the survival of the species. Nature does not design us to live forever, because that would be a waste of resources. It is easier and safer to dispose of bodies, reproducing sexually,gaining adaptations to an ever changing world. Evolution only cares about the gene, and not the individual. Death is the price we pay for sex.
We know that genes that harm us in old age contribute to our development early in life (antagonistic pleiotropy). Implication: if we alter or correct our bad genetic base in an attempt to live longer, we doom future generations.

Evolution designed us to stay healthy until just after the reproductive years; afterwards, we become disposable, and die.
(Women who experience menopause late in life live longer than average, due to the extra potential time they have to have children).

Doctor Rose found that by selective breeding of fruit flies, you could vastly extend the lifespan of the insect. He bred only the females who reproduced late-several generations later he had a very long lived bug.

The genetic allele for a human to live to be about one hundred thirty years old exists within our collective gene pool (we know this because some of us have reached this age). This allele is probably dormant in all of us-perhaps advances in gene therapy will bring it into expression, just like it was in the fruit fly.

How we age

Aging originates within the nucleus of the cell,inside the DNA molecule. This is where genes are located, strewn along chromosomes. This is the area where the commands to physically decline and die are issued. However-secondary processes are considered to be important on their own, and deserve attention.

One main theory of aging is called "Free radical oxidation cross linkage."
Free radicals are molecules in which one atom has gained an extra electron,making it highly reactive. Free radicals want to join other atoms or molecules in order to restore electrical balance (by getting rid of the surplus electron). Oxygen bearing free radicals are the most harmful; they literally tear the internal apparatus of the cell apart, targeting the mitochondria, the energy powerhouse of the cell. Once a free radical attaches to another molecule, a 'cross link' occurs. The cell becomes pinched in half, or "handcuffed," and can no longer function properly.
The overall effect of free radical damage is chemically identical to what happens when metal rusts.
Some people try to prevent this damage by orally consuming free radical scavenging substances; this is almost useless, because pills cannot survive the digestion process, get through the blood, past the outer cell membrane and into the inner membrane....without losing all potency.
A better way: augment our natural antioxidants (SOD,Catalase), or use genetic engineering to lessen the body's production of free radicals.

Another way we grow old is "Glucose browning." To produce the energy of life, we burn glucose, a process called glycosylation. Over time, glucose deposits or plaques accumulate in our cells/tissues, impairing proteins (collagen and elastin, mainly). Eventually, our muscles and skin becomes rigid; we experience difficulty in running, or even standing. Cells "brown" in the exact same way meat browns when its cooked.
The antioxidant SOD is known to be able to reduce the harm caused by glucose -plaques; the body can only produce a certain amount of SOD...Maybe in the near future we will identify the gene(s) responsible for the manufacture of SOD, allowing us to increase its rate of production.

The Autoimmune theory of aging states that death results from the systemic breakdown of the immune system and its components. It is hypothesized that if we could maintain our immune system at the level we experience at age fifteen, our resistance could keep us alive well past the century mark. Basically, the immune system is a biological structure that usually distinguishes self from non self. As this system declines, it begins to attack the body. Invading germs are not resisted, nucleic acids are assaulted, and newly formed cancer cells are no longer attacked. The key immune system cell- the lymphocyte- normally produce B and T cells in the bone marrow and the thymus gland. With age, the thymus shrinks, T cell production falls, and faulty repair and disease begins.
Research indicates that by injecting thymus hormones into the elderly we might significantly slow down the aging process.
( In the 1991 the New England Journal of Medicine reported the result of an experiment conducted by Dr. Daniel Rudman. He injected twelve men aged 61-80 with growth hormone 3x a week for six weeks. The men regained muscle mass, lost fat, had improved skin elasticity, lower cholesterol...these test subjects became physiologically younger).

Programmed cell death, or the 'Hayflick limit' theory of aging, states that cells can only divide a set number of times; once this limit is reached, we die. The command to stop dividing is located inside the cell...
As cell division occurs, some information is lost each time; protein synthesis becomes faulty, errors in mRNA transcription increase, and the Telomeres on the end of the chromosomes get shorter. When the chromosomes become too short, certain genes are allowed to express themselves, and the cell dies (Telomeres are stringy loops that keep the individual strands of DNA from interfering with each other). The enzyme telomerase keeps the telomere long, thus preventing cell death- Telomerase may be able to re-set the aging clock (this is why cancer cells are immortal).
Doctor Hayflick determined that the number of cell divisions that are available to us to be about fifty...subsequent studies show that by adding nutrients like nucleic acids or vitamins, the number of cell divisions can be extended to about 150-almost tripling their lifespan.

Our cells are programmed to die- except cancer cells. In 1951, a woman suffering from cancer checked into Johns Hopkins Hospital in Baltimore Maryland. A sample of her tumor was removed for analysis...the patient died, but her cancer cells were put into a petri dish and fed nutrients- this line of cancer cells is still alive today. The Hayflick limit does not apply to cancer cells, they can divide indefinitely.
Hopefully we will discover how to extend this ability to normal cells, without incurring the negative aspects of endless cell division.

We die because of a loss of information... Very soon, advances in genetic engineering will cure disease and extend our productive life. DNA has an enzyme that can repair other, damaged DNA- DNA polymerase. This enzyme methodically inspects the DNA helix for mutations,making corrections as it goes along. Some mutations are harmless, but many are deleterious; a few are deadly. Over time, humans have aquired several lethal mutations- diabetes, sickle-cell anemia, and cystic fibrosis are a few. In these cases, repair was inefficient.
In the near future, we might use partially disabled viruses as vectors to deliver altered genes into cells that are afflicted with disease. This method of repair might eventually be used to change the estimated 6 to 7% of our genes that are involved in the aging process. The altered gene would be placed into a virus, the virus would infect the cell, changing its DNA, hopefully bringing about the desired result.
problems with this approach include: concern over the safety of using a disabled virus...will the body accept the engineered gene, and if so, for how long? The most important obstacle is the in-ability to target specific cells to a high degree.

In 1997, Japanese scientists discovered a gene that keeps us young. When this gene is defective, Man quickly sucumbs to emphysema, osteoporosis, infertility, arteriosclerosis, etc. This gene codes for a blood protein that delays the onset of age related conditions. It is hypothesized that a decline in the efficiency of this gene is a cause of aging. Eventual viral vectored gene therapy will keep this gene functioning significantly longer than it does right now ( This gene has been named Klotho, after the Greek goddess who spins the thread of life).

Organ regeneration holds promise-scientists hope to learn how to re-grow human organs, the same way some lizards can re-grow their tail.
The human liver can be cut in half, and the remaining section can regenerate itself. Parts of the spleen have the same ability, and children below a certain age can re-grow their fingertips.
In 1998 in Fulda, Germany, researchers announced that they were able to trigger the growth of new heart blood vessels by injecting heart surgery patients with genetically engineered human growth factor, FG-1.
One day we may be able to re-grow whole organs, using undifferentiated fetal tissue/stem cells, in a manner similar to the way a developing embryo builds organs.

We can replace corneas, knees, bones, ears...Metal and plastic joints are available for replacement hips, shoulders, elbows, and fingers. Pacemakers and dialysis machines prolong the lives of thousands.
The computer-robotic/AI revolution holds the promise of blurring the distinction between Man and machine on a deeper level than our current prosthetic applications...
We might one day devise synthetic neurons to augment our own...Soon we might directly link up or hook up our brain to a computer. Our consciousnness will be down(up)loaded into a artificially intelligent computer, we might become free from the limitations of the body altogether. Copies of our cybernetic self could be built and scattered across the solar system and beyond...machines would repair our new metallic and silicon bodies eternally... we will never die.

Or- we could perfect cloning...find a way to accelerate the growth of our clones in a vat of special nutrients, transfering our memories and awareness into our new bodies as needed. Or a clone might be made, yet the brain removed before birth, and the body kept alive in the vat, to be used for spare parts as the need arises.

A clone-computer interface is almost inevitable.

Hopefully soon, within the next twenty years, the riddle of life will be solved, as advances in science reveal the recipe, and ultimately, the formula for eternal life. A combination of therapies will combine to make this the last mortal generation. After all, how can anyone be happy with something that has to end?

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