This is an edited version of a post in my blog – chromosomesandcancer.com. The back-story is that I was approached by a national current affairs program to do an interview on telomeres. Being a cancer researcher I thought the story might be about cancer. It turned out the focus was on cosmetics. How so? Having done some extra background reading I’ve tried to put together a balanced view of telomeres’ role in cancer and aging and how they might be manipulated to cure diseases caused by telomeres that are too short or too long.
Genes are strung together on a long molecule called DNA. Together the genes make up the instruction manual that controls the workings of each cell as well as the way the cells co-ordinate with each other. (Have a look at Abby Buchwalter’s post for a good description of a cell in simple language.) There are 46 of these long strings of DNA in each of our cells (with a few exceptions). When a cell finishes growing and divides to become two cells, these 46 strings of genes fold up to become recognizable chromosomes – we can see these with a microscope.
At each end of a chromosome there’s a short stretch of DNA called the telomere. This caps the chromosome to protect it from eroding or from sticking to other chromosomes. Our telomeres start out at a set length in a fertilized egg. A tiny part of the telomere is lost every time a cell divides, so our telomeres get shorter as we grow older. Other factors, such as extreme psychological stress, and toxins such as chemotherapy, are also thought to cause telomere shortening.
When telomeres get too short, the chromosomes can join together to become one abnormal chromosome. Cells with dangerously short telomeres usually self-destruct. But if the cell escapes self-destruction, these joined-together chromosomes can be unstable and risk making the cell cancerous – outgrowing its neighbors and dividing indefinitely.
Here’s the paradox – short telomeres can cause cancer, but cancers re-lengthen their telomeres to become immortal.
Cancers usually lengthen their telomeres by activating an enzyme (a protein which causes chemical reactions) called telomerase. It’s been suggested that shortening the telomeres of cancer could be an effective treatment. Some researchers are trying to do this by destroying the telomerase in cancer cells.
Besides cancer, short telomeres are thought to cause other diseases that we associate with aging, such as osteoarthritis, diabetes, and cardiovascular disease. Some people are born with short telomeres – and they can get a similar range of diseases. In one interesting study, mice without telomerase aged prematurely, but they regained their health when this enzyme was replaced. So there are also researchers looking at the possibility of using telomerase to cure diseases that are associated with short telomeres, or to reverse the effects of aging. TA-65® is a chemical that can activate telomerase. It’s already available in some cosmetics, where it’s promoted as an anti-aging treatment. This same chemical is being tested for use as a treatment for diseases linked to aging and short telomeres.
Drugs that lengthen or shorten telomeres will need to be tested carefully to make sure they don’t have unwanted side effects, before they can be used for treating medical conditions or as an anti-aging treatment. In particular, because telomere lengthening allows cells with abnormal chromosomes to become immortal, artificially lengthening telomeres could be a cancer risk. There’s debate about this, but obviously it would need to be pretty clear that the risk is negligible before telomere lengthening drugs are used as an anti-aging strategy. TA-65® is allowed in cosmetics because they aren’t governed by the same regulations as drugs.
There’s a strong link between short telomeres and stress-related diseases. There’s also evidence that drug-free measures like reducing stress, exercise and an improved diet, can stop or even reverse premature telomere shortening. These are safe and available now.
Telomeres were originally a niche specialty area of basic science with no obvious health implications. Telomere research now gives some hope to people with cancer and other diseases, and even people who are hoping to find the key to eternal youth.
REFERENCES AND FURTHER READING (THESE ARE OPEN ACCESS ARTICLES – THEY ARE FREELY AVAILABLE)
C. Buseman 2012. Is telomerase a viable target in cancer? Mutation Research 730:90-97
E. Callaway 2010. Telomerase reverses ageing process. Dramatic rejuvenation of prematurely aged mice hints at potential therapy. Nature 28th November 2010 (published online).
B. de Jesus et al. 2011. Aging by telomere loss can be reversed. Cell Stem Cell 8:3
C. Harley et al. 2011. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Research 14:45-56.
R. MacKinnon and L. Campbell 2011. The role of dicentric chromosome formation and secondary centromere deletion in the evolution of myeloid malignancy. Genetics Research International Article ID 643628
T. Morin. https://www.dayspamagazine.com/article/spa-products-tale-telomeres A balanced article on telomeres in Dayspa Magazine online.
E. Blackburn and E. Epel 2012. Too toxic to ignore. Nature 490:169-171 (about stress, disease and telomere shortening). Note, Elizabeth Blackburn is Australia’s only female Nobel Prize winner (in science at least) – she shared the prize for Physiology or Medicine in 2009 for her discovery of telomeres.
B. de Jesus et al. 2013. Telomerase at the intersection of cancer and aging. Trends in Genetics (available online 19th July 2013)