Professor Column

On the first morning of this century, a futurist predicted that 80% of girls born this year would live till the year 2100. Are most of us really able to attend our sons Kohee (a seventieth birthday party). We have to wait till the end of this century to see whether it is a correct prediction, but current trends in worldwide life expectancy say it a possibility. Even in Korea where the number of centenarians are close to a thousand, it doubles each year. How long a man can live has been one of the most frequently asked questions throughout human history. Now, do we know what our maximum life span is and how it is determined? Not yet. Gerontological science today is in its beginning stage and is not thorough enough to answer these questions. However, we have some clues on why we get physically deteriorate as we age.
All the physical progresses such as body growth, development, aging, and death are determined by complex interplays of a hundred trillion cells that compose in our body. Therefore, the fates that these cells experience also determine our health and longevity. And so far, studies on cells have provided some important clues on the mystery of aging.

If one takes out a small patch of his skin, and incubates it under appropriate conditions, he can get a spread of cells that composed the skin. These cells can keep dividing to double their population for a while, and then population doubling (PD) slows down until it stops completely. This stage is called cellular senescence. Cells can live for a while in this senescent state, but they eventually break apart and die. Interestingly, there is a correlation between the bodily life span and the cellular doubling potential, which determines cellular life span. The human life span is approximately 100 years, while the life spans of giant sea turtles and mice are 150 years and 24 months, respectively.

Maximum numbers of PDs of cells isolated from each animal are 50, 100, and 10, respectively, and are roughly proportional to the life span of individual body. Furthermore, cells isolated from a human fetus can divide for 80 PDs, while those from the middle aged and the old can divide for 40 PDs and 15 PDs, respectively. These findings imply that cellular population doubling potential is limited to a certain number for each animal, and has good correlation with the body life span. They also suggest that in cells, there may exist kinds of machinery that count how many times a cell went through population doublings. This putative machinery is sometimes called the aging clock. There actually is a good candidate for this aging clock in our cells. Every cell has chromosomes (human cells have 46 of them) in the nucleus, and they are made of long strands of DNA that carry the genetic information. Upon each cell division, the ends of the chromosomes get a little shorter each time. And as you can imagine, this cannot keep going on forever. Once the length of the chromosomes gets short beyond a certain critical point, the cells are not able to get all the genetic information, become defective, and eventually die. Therefore, it is very likely that this chromosome shortening would limit the number of cell division, and thereby, the cellular life span.

Now, if this is what determines our life span, then, why would person live over a hundred years while the other one dies only after his seventieth birthday? The aging clock may be rendered to run fast. Then, what would make it run fast? They must be certain extrinsic factors that affect the health and performance of our cells. One widely accepted theory on why cells gradually lose their function is the so-called Damage accumulation theory. One way to define living organism is whether it maintains metabolism, which is a collective term for numerous chemical reactions that produce energy and many building-block materials. Oxygen is an essential molecule for many parts of these reactions, and therefore is indispensable for life. However, during metabolisms, 2 % of oxygen molecules get changed into very reactive ones, and oxidize many important cellular materials, which normally are not targets for oxygen. We all have seen oxidation turn strong iron into very brittle red fragments.

One example of such deleterious changes can be seen in oxidation of cell membranes. Cellular membranes are made of lipids, which serve not only as packaging material for cellular contents, but also provide transportation routes for food chemicals, hormones, and wastes in and out of cell. Oxidized membranes lose their function as a transport barrier as you can imagine by an example of the deteriorative change of oxidized oil. This deteriorative damage by oxygen (oxidative damage) occurs also in DNA, which is our genetic material, and in carbohydrates and proteins, which make up building materials and catalytic workers in cell. And as we age, more oxidative damage would accumulate in cells, causing malfunctions in many aspects of cellular activities and eventually result in cell-death. Our cells have means to fight against reactive oxygen molecules, i.e., chemicals and enzymes with anti-oxidant functions. We also consume chemicals that have anti-oxidant activity. The vitamins, C and E, are such nutrients.

There seems to be some genes that play certain roles in ageing normally. People suffering premature aging diseases such as Werners syndrome or Down syndrome have certain genetic defects. But, it is not likely that those genes control the aging process itself. Judging from the theories and findings so far, it appears that our maximum life span is governed by certain aging clock function in our cells, and its rate is likely determined by how well we protect our cells from oxidative damage. Current knowledge tells that the aging clock is innate, and you cannot rewind it. But, you may extend your life slightly beyond or live healthy during your own predetermined life span. For this, keep exercising, but not severely. Exercise keeps our cardiovascular system strong. But, not many field athletes live long. Eat less. Mice fed less do live one and half times longer than the well-fed ones. And finally, take less meat and more vitamins C and E.


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