Recent studies are changing what scientists have long thought about telomeres, which are repetitive sequences of DNA that cap the ends of chromosomes. Telomeres get shorter with each round of cell division, until they cannot get any shorter and at that point, cells stop dividing. Telomeres are thought to be closely linked to aging and certain diseases. New research has studied seventeen individuals from five different families who carried mutations in a gene called POT1, which is associated with telomeres. The unusually long telomeres seen in these individuals do not confer longevity; instead, carriers of these mutations tend to get certain types of tumors and a disorder called clonal hematopoiesis. The research has been reported in New England Journal of Medicine.
"Our findings challenge the idea that long telomeres protect against aging," noted study co-author Mary Armanios, M.D., a professor at Johns Hopkins University School of Medicine, among other appoinments. "Rather than long telomeres protecting against aging, long telomeres allowed cells with mutations that arise with aging to be more durable."
Experiments using cell growing in culture have suggested that long telomeres will promote longevity, but in people, abnormally long telomeres are not particularly helpful to cells. Armanios said that when cells have extremely long telomeres, they tend to accumulate genetic mutations and seem to encourage the development of tumors or benign growths that should be controlled by normal processes that shorten telomeres.
In twelve of the seventeen study participants, there were cancers such as lymphomas, melanoma, leukemia, and uterine fibroids, as well as goiters. Some people had more than one condition.
Telomere length was measured for thirteen of the seventeen study participants, and these people were found to carry telomeres that were about 90 percent longer than healthy individuals, and nine had telomeres that were longer than 99 percent of telomeres carried by the general population.
Six of the individuals had some signs of youthfulness, such as a delay in hair graying. But they did carry more mutations in their blood cells. Some people with POT1 mutations had blood cells with as many as 1,000 other mutations. This dramatic increase in blood cell mutations could explain why these people tend to have a higher risk of blood cancers.
The research also indicated that the unusually long telomeres tend to get shorter at a slower rate compared to people whose telomeres are the typical length.
Another recent study has shown how our expectations of telomeres do not seem to be matching reality.
Sources: Johns Hopkins University School of Medicine, DeBoy et al New England Journal of Medicine 2023, Vassiliou et al New England Journal of Medicine 2023
