Investigating telomeres and what they mean for aging-related diseases

When molecular biologist Carol Greider was 25 years old, she was studying a minute pond creature and its telomeres, the tips of its chromosomes. Greider knew that as chromosomes naturally divided, their telomeres became shorter, but in this particular animal they did not.

She wondered why, and guessed that an enzyme was involved. Her hunch panned out. According to Greider’s research, the enzyme, telomerase (pronounced “ta-LAW-mer-ace”), helps maintain the length of telomeres, replenishing them with each cell division. This discovery led to the 2009 Nobel Prize in Physiology or Medicine for Greider and two colleagues, and to further study of the connection of telemeres to diseases associated with aging, such as pulmonary fibrosis, and to some cancers.

(Handout) - Molecular biologist and Nobel prize winner, Carol Greider, discusses the connection between telemores and age-related diseases.

Greider, now 51, is director of molecular biology and genetics at the Institute for Basic Biomedical Sciences at Johns Hopkins School of Medicine. She recently spoke to The Post about telomeres and whether understanding how to manipulate them may someday lead to treatments of age-related diseases.

— Laura Hambleton

What are telomeres, exactly?

They protect chromosomes. They are like the tip of shoelaces, that plastic piece that protects the shoelace from unraveling. With age, telomeres naturally shorten. [But] just looking at someone’s telomeres without their age doesn’t tell you much.

Tell me about discovering how telomerase works.

We were working in this single-cell animal called a tetrahymena. It is a pond-dwelling creature, like a paramecium. A single cell has 40,000 telomeres, whereas a human cell only has 92. What I set out to do was make an artificial telomere in the test tube, then see if that telomere could be elongated. I did that by making a cell extract from the tetrahymena. If a tetrahymena had 40,000 chromosomes, it would have a lot of the stuff needed to elongate telo­meres. And it turns out that was correct. It was using this tetrahymena where I discovered this enzyme called telomerase.

What are some of the implications of your discovery?

The first implication is cancer. A cancer cell is a cell that is dividing many more times than it should. It has to solve the telo­mere problem because every time that cells divides, the telomere shortens. It turns out over 95 percent of the different cancer types have more of this telomerase enzyme, so it solves the telomere problem. If you could block this enzyme, then you may be able to block the growth of cancer cells. We’re not at a stage where we have a clinical inhibitor of telomerase. There are some that have been tested, but the biology [of different cancers] is a little bit more complicated.

The other place where telo­meres play a role is in normal cells in the body that have divided many times just for normal upkeep of the body. It turns out human families where you have inherited diseases that don’t have enough telomerase, they have bone marrow failure. The bone marrow is an easy example to understand because the bone marrow is where all the blood comes from. Every day there are new blood cells that are born and circulate around.

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