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Why We Grow Old And Cancer Cells Don't

With one very special exception, every cell in your body is a prisoner to developmental decisions made long before birth, committed without choice to being a particular tissue -- if muscle, every time the muscle cell divides, its descendents are muscle cells too. After about 50 divisions (the number varies with the kind of tissue) the tissue cells die. Only the cells whose descendents become gametes -- eggs and sperm -- escape this fate. Called embryonic stem cells, they are immortal, and able to form every kind of cell in your body. Last year scientists learned how these unusual cells escape death, and in the last few months they have learned how to culture them in the laboratory. This long-sought advance has at last given us an answer to the question of why we grow old.

As with many scientific advances, progress came when scientists learned to ask the right question. Dr. Leonard Hayflick, now of the University of California, San Francisco, has that honor. He discovered in 1961 that when cells are taken from the body and grown in tissue culture on a laboratory dish, there is a limit to how long the cell line lives -- after about 50 divisions, the aging cell line dies. Called the Hayflick limit, this inability to survive past a certain number of cell divisions has puzzled developmental biologists for decades. What causes the cells, after so many successful divisions, to abruptly throw in the towel? How does a cell know its time is up?

Over the last 18 months we have learned the answers to these questions. The key breakthrough came when researchers succeeded in making cells violate the Hayflick limit -- in essence, they learned how to make human body cells growing in tissue culture immortal. The secret to immortality proved to be a short tag of DNA stuck on the tips of the cell's chromosomes. Called a telomere, this segment of DNA plays a key role in cell division. The telomere provides a place for the cell's DNA-copying machinery to latch onto the chromosome when the time comes each generation for the chromosomal DNA to be copied into daughter chromosomes. However, every time the machinery attaches, the short bit of the telomere where the machinery sits down on the DNA is not itself copied, so the telomere gets a little shorter each time the cell divides. When the telomere reaches a minimal length after some 50 divisions, the cell can no longer replicate its DNA and lapses into senescence.

So how were scientists able to make cells immortal? The secret to producing cell immortality lay in their realizing that all cells possess a gene, known as the telomerase gene, which can add DNA back to the tip of telomeres, restoring them to their original youthful length. In almost all cells this gene is turned off early in development, rendered permanently inactive in an event that commits that cell to eventual sure death. This sad decision is a very necessary one, as it protects the adult human body from developing tumors whenever a cell's division controls are disabled. Only when this added protection against runaway growth is also lost, the switch stopping production of telomerase turned back "ON," can a cell proceed beyond a few divisions and become a cancer cell. Cancer cells are immortal because they produce telomerase.

In the human body, only two kinds of body cells are immortal, able to divide without limit. Cancer cells are one. The other kind of immortal cell is the embryonic stem cell. The cells derived from recently fertilized human eggs, before they implant in the uterus, are called embryonic stem cells and have the power to develop into all of the 210 different kinds of cells in the body. Most of them last only fleetingly as stem cells, soon turning into more specialized cells and loosing their telomerase activity. A few, however, are set aside, protected from the influences that trigger differentiation and shutting down of the telomerase gene. Called germ line cells, these embryonic stem cells have a fully functional telomerase gene and continue to divide, producing eggs and sperm that in their turn produce more stem cells in the next generation.

Research into stem cells, while very controversial because the cells are obtained from discarded embryos or aborted fetuses, offers the tantalizing promise of replacing injured tissue. Imagine being able to replace the lost brain tissue in an Altzheimer's patient, the cardiac muscle tissue damaged in a heart attack, or the skin of a burn victim. We all must grow old, but prehaps with the aid of stem cells some of our body parts can evade the process.

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