When I hear that some gene, or protein has the potential to prolong our life, I am doubled very much. Our bodies wear out and any effort to reverse this biological process risks turning up cancer. As the telomere caps on chromosome ends wear down, Cells would lose the ability to divide. So longer telomere caps good? Shorter telomere caps bad? It’s not that easy.
A new research conducted by UC San Francisco (UCSF) scientists reveals that 2 common gene variants link to long telomeres, the caps on chromosome generally thought to be a sign of slow biological ageing, also raise the risk of deadly brain cancers known as gliomas.
Identify “culprit” gene
In this research, researchers analyzed genome-wide data from 1,644 glioma patients and 7,736 healthy control individuals, including some who took part in The Cancer Genome Atlas project sponsored by the National Cancer Institute and National Human Genome Research Institute. This work identify risk alleles for glioma near TERC and TERT that also associate with telomere length.
The genetic variants, in the TERT and TERC genes known to regulate the action of telomerase, are respectively carried by 51% and 72% of the population. Because it is somewhat unusual for such risk-conferring variants to be carried by a majority of people, the researchers propose that in these carriers the overall cellular robustness afforded by longer telomeres trumps the increased risk of high-grade gliomas, which are invariably fatal but relatively rare cancers.
“Though longer telomeres might be good for you as a whole person, reducing many health risks and slowing aging, they might also cause some cells to live longer than they’re supposed to, which is one of the hallmarks of cancer,” said lead author Kyle M. Walsh, PhD, assistant professor of neurological surgery and a member of the Program in Cancer Genetics at UCSF’s Helen Diller Family Comprehensive Cancer Center.
Previous Research on telomere
UCSF’s Elizabeth Blackburn, PhD, shared the 2009 Nobel Prize in Physiology or Medicine for her pioneering work on telomeres and telomerase, an area of research she began in the mid-1970s. In the ensuing decades, untangling the relationships between telomere length and disease has proved to be complex.
In much research, longer telomeres have been considered a sign of health — for example, Blackburn and others have shown that individuals exposed to chronic stressful experiences have shortened telomeres. But because cancer cells promote their own longevity by maintaining telomere length, drug companies have searched for drugs to specifically target and block telomerase in tumors in the hopes that cancer cells will accumulate genetic damage and die.
In some of these cases, the disease-associated variants promote longer telomeres, and in others shorter telomeres, suggesting that “both longer and shorter telomere length may be pathogenic, depending on the disease under consideration,” the authors write.
1. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nature Genetics on June 8, 2014
2. Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett. 2005 Feb 7;579(4):859-62.