Telomerase, Telomeres, Cancer and Aging

The nucleus in our body cells contains thread-like structures called chromosomes, which are made of a molecule of DNA (deoxyribonucleic acid) and proteins. The DNA molecule contains the genetic code. At each end of a chromosome is a region called a telomere, which acts as a cap to protect the chromosome ends from damage and to stop the ends of different chromosomes from joining together.

Before a cell divides, the chromosomes in the cell are replicated so that a copy of each chromosome can go into each daughter cell. Telomeres shorten every time chromosomes are copied. The decrease in telomere length is believed to influence cancer and body aging.

Cells do have a way to fight telomere shortening. A cell enzyme called telomerase helps prevent the telomeres from decreasing in length. Most cell types make very little telomerase, while some make far more.

The genetic code in a DNA molecule is composed of a sequence of nitrogenous bases. These bases are adenine (A), thymine (T), cytosine (C) and guanine (G). Just as the letters of the alphabet can be arranged in specific sequences to produce different words, the four nitrogenous bases in a DNA molecule are arranged in specific sequences to code for different amino acids. When the cell “reads” the code in the DNA, amino acids specified by the code are brought into position and joined together in the correct sequence to make proteins. A DNA molecule contains two strands of bases paired together, but only one strand is read when proteins are being made.

Some of the base sequences in DNA don’t code for amino acids and are therefore referred to as “non-coding” DNA. This includes the bases in the telomeres. In the telomere region of a chromosome, the DNA bases are repeating sequences of TTAGGG on one DNA strand paired with AATCCC on the other strand. Generally, a person’s telomeres are longest at birth, and gradually decrease in length as the person ages. Telomeres are needed to prevent the coding portion of the DNA from shortening.

When its telomeres are very short, a cell no longer divides. The cell experiences genetic damage, ages and eventually dies.

The enzyme known as telomerase is present in a very small amount in most of the body’s cells. Telomerase lengthens telomeres by adding bases to the end of chromosomes. Egg and sperm cells have a relatively high level of telomerase activity.

Cancer cells multiply rapidly, which results in shortened telomeres. However, telomerase becomes active in cancer cells, preventing the telomeres from becoming so short that the cells can no longer survive. If scientists could block the activity of telomerase they could force the cancer cells to die. Laboratory experiments have shown that tumor cells do die when they can no longer make telomerase. However, inside a human body, inhibiting telomerase might interfere with the production of rapidly dividing cells like the parent cells that produce blood cells, reproductive cells and cells that heal wounds or fight infections.

There is a great deal of debate and uncertainty about the factors that cause human aging. Scientists have observed that older people have shorter telomeres, but are not sure how big a role this plays in the aging process.

In 2010 a group of scientists genetically engineered mice to be unable to make the telomerase enzyme. As a result, the chromosomes of the mice shortened and the mice aged much more quickly than normal mice. The spleen, testes and brain shrunk. In addition, the mice developed disorders that in humans are more common in older people, such as osteoporosis, diabetes and nerve degeneration.

The scientists then gave the mice a chemical which turned on telomerase production again. The chemical reversed the aging effects and caused degenerating organs to become active once more. Even the brain enlarged, and the cognitive abilities of the mice improved.

Although the results of the mouse experiments are very impressive, some scientists are uncertain that similar results will be found in humans that are given telomerase. They point out that the genetically engineered mice didn’t age normally but were stimulated to grow old by artificial means. Another concern about using telomerase as a potential anti-aging drug in humans is that it might support the replication of cancer cells.

Other factors are believed to affect the aging process in humans in addition to telomere shortening. One of these factors may be oxidation, a process in which certain chemicals containing oxygen damage DNA, proteins and fats in the body. These effects are sometimes known as “oxidative stress.” Another contributing factor to human aging may be the accumulation of advanced glycation end products (AGEs) in the body. These substances form from the reaction of sugar with proteins or fats. It's thought that they may contribute not only to aging but to certain diseases that appear in older people.

In the future, reducing telomere breakdown with telomerase may be one of several techniques used to increase the human lifespan, provided it can be shown that adding telomerase to the body doesn’t increase the cancer risk.