To Live Forever ? (The Physics of Aging)

To Live Forever ? (The Physics of Aging) How Science Will Revolutionize 21st Century.

by : Aria Ratmandanu 

"Happy Birthday to Science and Reason, Science is a beautiful gift to humanity" - Aria Ratmandanu

     Central to a “unified theory of aging” are physics, information theory, and genetics. There is, first of all, the Second Law of Thermodynamics, which states that disorder (or entropy) must increase in any closed system. In short, things run down. In the words of George Harrison: “All things must pass.” Our bodies, our machines, our creations, even the universe, must eventually wear out.

     Applied to the universe, it means the stars will eventually exhaust their nuclear fuel, plunging temperatures down to nearly absolute zero, creating a dismal universe consisting of dead stars, black holes, and cold formless gas. The destiny of the universe is to reach a state of maximum chaos.

      In our bodies, this increase in entropy is manifested by the loss of information. Each time our cells reproduce or are battered by toxic chemicals, tiny errors in the information of our DNA begin to accumulate, until our cells can no longer repair themselves and function normally. Eventually, the Second Law of Thermodynamics catches up with our cells, and aging becomes irreversible. As entropy increases, our cells no longer have their original resilience and vitality because of accumulated information loss. Hayflick calls this “molecular mischief”—i.e., the idea that aging is caused by the gradual buildup of errors in our molecular code, which slowly reduces the efficiency and vigor of our cells. Aging may be caused by the loss of our ability to repair this molecular damage.

     If the Second Law is an ironclad law of physics, at first it seems a hopeless task to try to reverse aging. But there is a loophole in the Second Law: it refers only to a “closed system.” This means we can have a tradeoff: we can reduce entropy in one area (and hence reverse aging) as long as we increase it in others, so the total amount of entropy still increases.

   For example, the creation of a baby represents a massive decrease in entropy. But this is compensated for by the chaos that the baby produces elsewhere (in the stress on the mother’s body, in the increased consumption of food, and in the vast resources needed to create the baby). In other words, the loophole in the Second Law may be exploited by the age genes, whose purpose is to repair the molecular damage caused by aging.

    When middle-aged people, bemoaning creaky joints and aching muscles, claim they are “getting rusty,” they may be closer to the truth than they realize. One of the most seminal ideas about aging is the oxidation theory, which states that aging is driven by the same process that makes iron rust, silver tarnish, and fires burn—namely, oxidation, a volatile, corrosive process caused by unleashing the chemical force locked within the oxygen that we breathe in the atmosphere. Oxidation is one important way in which the Second Law is manifested in our bodies.

      On the one hand, oxidation is the energy source that fuels our body. When we take a deep breath, the oxygen filling our lungs filters down into our cells, which uses the chemical ATP (adenosine triphosphate) to carefully release the energy necessary to flex our muscles and move our bodies. However, there is a dark side to this process. Unchecked, oxidation by itself also wreaks havoc in our system, creating “free radicals” in our body which, like a monkey wrench thrown into a finely tuned machine, disrupts cell functions. These volatile free radicals, because of their electrical nature, can rip apart proteins and nucleic acids, disrupting the delicately balanced machinery of the cell.

     That aging could be linked to the damage caused by oxidation was first proposed by R. Gerschman in 1954, and further advanced by Denham Harman of the University of Nebraska. They reasoned that if aging was caused by oxidation brought on by free radicals, then aging might be slowed by the neutralizing action of antioxidants. The most common “antioxidants include vitamins E, C, and A, as well as beta-carotene, superoxide dismutase (SOD), catalase, and glutathione peroxidase.

        Antioxidants are commonly found within the body as well as in our food. (Antioxidants are often added to cereals and baked goods; they are used to slow down the oxidation process, which causes the food to become rancid and stale. In controlled experiments, the life spans of certain animals (mice, fruit flies, rats, nematodes, rotifers, and the mold called neurospora were shown to be lengthened with antioxidants. In fact, the life span of mice can be increased by 30 percent. These animals did not become decrepit like poor Tithonus. Studies have shown that antioxidants postpone the appearance of cancer, cardiovascular disease, and diseases of the nervous system and the immune system. One testable prediction of the oxidation theory is that animals with short life spans should have higher levels of free radicals. Laboratory studies have borne this out. The oxidation or free radical theory of aging may give us a crucial clue to how, at the molecular level, damage accumulates in our bodies. But still the question remains: how do we slow or even prevent the damage?”

From the Present to 2020: Hormones, the Elixir of Life ?

    By far the most painless and medically proven way to increase our life expectancy (and prevent the country from going bankrupt from skyrocketing medical expenses) is to lead a healthy life—i.e., quit smoking, exercise regularly, and eat a low-fat, low-cholesterol, high-fiber diet. Study after study has shown that the American people are grossly indulgent in their lifestyle, leading to a host of chronic illnesses.

     However, medical research is gradually changing its opinion about one of the more unsavory areas of biogerontology research, hormone therapy. Traditionally, hormone therapy has had the reputation of being a haven for charlatans, faddists, and outright crooks. The field of hormone treatments has a colorful history, with scores of scandalous and even hilarious encounters with hormone quacks making preposterous claims.

   In the 1920s, a colorful fundamentalist preacher named John “Doc” Brinkley claimed that transplanting the testicles of goats and other animals could reverse aging. Thousands of elderly people heard his claims via the radio station he founded and made the pilgrimage to his clinic in Kansas. He “became so wealthy and powerful that he even ran for the governorship of the state of Kansas (he lost).

    However, hormone therapy is rapidly shedding its snake-oil image and entering the ranks of rigorous science with a series of new studies. In fact, with a boost of $2 million from the National Institute on Aging of the NIH, nine research teams are currently conducting studies on “tropic factors” like hormones which promote growth and maintenance of tissue.

From now to 2020, hormone therapy may blossom into an important way to control some of the ravages of aging and protect against disease (although it will probably not extend our maximum life span).

     It’s well known that women are protected from many of the diseases and symptoms of aging via the sex hormone estrogen during their reproductive years. However, when a woman undergoes menopause, the levels of estrogen drop and bone loss and heart disease increases. Evolutionary biologists have concluded that women were not meant to live very long after menopause. Charles Hammond of the Duke University Medical Center put it bluntly when he said, “At the turn of the century, women died soon after their ovaries quit.

     Already, estrogen is the number one prescription drug in the United States and also one of the most exhaustively studied. The famous Nurses Health Study, which followed 120,000 nurses for more than ten years, found that postmenopausal women who received estrogen had half the incidence of heart disease. Other studies have shown that in older women estrogen reduces hip fractures by 50 percent, improves memory, lowers the incidence of colon cancer by up to 55 percent, and maintains collagen that keeps the skin supple and moist.

     Furthermore, the biomolecular revolution has deciphered how hormones like estrogen work. They perform their magic by stimulating the genes of the target cells to produce certain proteins (like prolactin) that carry out specific functions in the body. In other words, hormones act to “turn on” certain genes within the cell.

Beyond 2020: It’s All in Our Genes

     Beyond 2020, scientists will be searching for the “age genes” which may retard or repair molecular damage due to aging and the Second Law of Thermodynamics. Assuming that such genes exist and can be isolated, then perhaps through gene therapy the process of aging may be arrested and one’s maximum life span can be extended.

       One intriguing clue to the puzzle was provided by Michael Rose of the University of California at Irvine. By selective breeding, he was able to increase the life span of fruit flies by 70 percent. “That’s what makes the field very exciting now—we are doing things that work,” he says. His “superflies” were also much more physically robust than ordinary fruit flies. Significantly, he has also found that his long-lived flies produced more quantities of the antioxidant superoxide dismutase (SOD), which helps to neutralize the effects of the dangerous free radical superoxide. Do the flies have an “extended life span because they are able to resist the degrading effects of oxidation ?.

In 1991, biologist Thomas Johnson of the Institute for Behavior Genetics at the University of Colorado stunned the scientific world with his announcement that, for the first time in history, he was able to genetically change the life span of another organism. He isolated within the nematode, a tiny worm, a new gene which he auspiciously called age-1. By manipulating this gene, he could increase the three-week life span of the nematode by 110 percent, a dazzling achievement which seemed to prove, once and for all, that, at least for certain organisms, there is an age gene and that it can be systematically manipulated.

     As Johnson says: “If something like age-1 exists in humans, we might really be able to do something spectacular.” His next goal is to see if any counterpart to age-1 lies within the human genome. Others scientists have produced encouraging results as well. Cynthia Kenyon of the University of California at San Francisco has shown that worms (Caenorhabditis elegans) with a mutation in the gene daf-2 live more than twice as long as normal, 42 days “to the usual 18 days. She noted that the mutated worms “looked pretty happy and healthy” even as their normal counterparts were dying off of old age.

     Siegfried Hekimi of McGill University in Montreal produced mutant worms that lived five times the normal life span, a record for any animal. “These animals are as close to immortality as worms can get,” he said. He isolated four genes which slowed down not only aging but everything else in the worm, including eating, cell division, and swimming. He called them “clock genes.

Aging Research from 2020 to 2050

How will all this progress develop in the future?

     The mounting evidence for age genes which influence the aging process is by no means conclusive, but it is quite impressive, coming from a variety of independent research, from aging in worms and fruit flies to antioxidants and gene repair mechanisms, and human mutations. Still, the connections are circumstantial.

         Christopher Wills, professor of biology at the University of California in San Diego, thinks that by 2025 science will likely isolate the mammalian age genes in mice. We share 75 percent of our genes with mice and have much of the same body chemistry; this is a strong reason to believe that an age gene found in mice could also be at work in humans. If such genes are located, the next step would be to find out if these age genes have their counterparts in humans. Wills believes that if they are found in humans, they may extend the human life span perhaps to 150 years.

       But by 2020, when personalized DNA sequencing becomes widespread, a second tactic may prove fruitful as well. By analyzing populations of healthy individuals in their nineties and beyond, it will be possible to use computers to compare their genetic backgrounds and cross-check for similarities in key genes which are suspected of influencing aging. A combination of studies on the DNA of long-lived animals and the personalized DNA sequences on elderly individuals may considerably narrow down the search for the age gene.”

Animals That Are “Immortal"

       Before the biomolecular revolution, scientists were forced to speculate about human aging from indirect clues. Perhaps the simplest clues to aging came from the animal kingdom and evolutionary biology.

      All mammals eventually reach a fixed body size as they age; however, certain animals which do not have a fixed body size (such as some lobsters, flounders, sturgeons, sharks, and alligators) simply increase in body size with time but show no noticeable sign of aging. These animals are “immortal” in the sense that their aging process is so slow that it is either nonexistent or too slow to be measured reliably in the laboratory. Many textbooks incorrectly state that these animals have a finite life span like other animals. These texts confuse “life expectancy” with “life span.” Life expectancy refers to the average age an organism lives until it dies of disease, predators, or starvation, whereas life span refers to the maximum age an organism can live if these external causes of death are removed. This is the reason why we do not see 500-year-old alligators the size of houses prowling about—because they have succumbed to the perils of living in the wild.

      However, when these animals are kept in zoos, “they are largely immune from these external factors and simply grow indefinitely, with almost no diminution of their physical functions after reaching sexual maturity. The classic example of this is the flounder. The male flounder reaches a fixed size and ages normally. However, the female flounder grows indefinitely and shows no signs of aging or loss of function with time.

      The existence of animals with no fixed life span seems to indicate that “age genes” do exist. Apparently, the cells of these animals never lose their vigor or their ability to reproduce.

From a strictly evolutionary point of view, however, aging may serve a purpose. Nature has little use for an aging animal well past his or her vital, childbearing age; such an animal is a drain on the rest of the herd or pack. Perhaps nature planned for organisms to gracefully age and die, leaving precious resources for the next generation to perpetuate the species.

        Generalizing from lower animals to humans is always dangerous, but aging in humans also seems to obey an evolutionary path. Paleontologists, analyzing the remains of our ancestor Australopithecus, are now convinced that our lineage separated from other primates about 5 million years ago. Within that 5-million-year period, our life span has more than doubled compared with our primate cousins. In evolutionary terms, in almost a blink of an eye our brain size, body weight, and life span ballooned, which is extraordinary for any species in the animal kingdom. The relative brevity of this remarkable expansion indicates, but does not prove, that our life span is basically controlled by a handful of age genes. Since we share 98.4 percent of our genes with the chimpanzees, by systematically focusing on the genes that separate us from our primate cousins, perhaps we can locate the age genes among them.