The shortening of human telomeres – caps that protect our chromosomes from deterioration – has been associated with aging and disease. Now, researchers from the Stanford University School of Medicine, CA, say they have found a way to lengthen these telomeres, potentially opening the door to new treatments for many age-related and genetic conditions.
The research team, led by John Ramunas, PhD, and Eduard Yakubov, PhD, publish their findings in The FASEB Journal.
Chromosomes are thread-like structures situated at the end of DNA strands that contain all our genetic information. Telomeres protect our chromosomes from becoming damaged during cell division.
However, telomeres become shorter with each cell division and can reach a point where they are no longer able protect the chromosomes, leaving them open to deterioration. This leads to aging and disease development.
Studying human cells in the laboratory is important for finding new ways to treat such diseases, but the team says the shortening of telomeres makes this challenging; it only allows researchers to monitor cells over a few divisions before they die.
But now, Ramunas, Yakubov and their team say they have found a way to extend the length of telomeres, which could increase the number of human cells available for studying.
To increase telomere length, the team used a modified type of ribonucleic acid (RNA) that contained the coding sequence of TERT.
TERT is the active component of telomerase – an enzyme expressed by stem cells that maintains the health of telomeres as they are passed to the next generation. Though stem cells express TERT, the researchers note that most other cell types do not.
In their study, the researchers explain that introducing as few as three applications of the modified RNA (called modified TERT mRNA) to human cells over a few days increased telomere length by up to 10%. Young humans possess telomeres that are around 8,000-10,000 nucleotides long, the team notes, but the modified TERT-encoding RNA increased telomere length by around 1,000 nucleotides.
What is more, the researchers say that human skin cells treated with modified TERT mRNA divided around 28 more times than those that remained untreated, while treated human muscle cells divided around three more times.
Ramunas says the team was pleasantly surprised to find that modified TERT mRNA effectively increased telomere length.
“Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase, which could be deleterious,” he adds.
“In contrast, our technique is nonimmunogenic. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent.”
The researchers say their new technique could lead to new treatments for age-related diseases and genetic conditions that are associated with telomere shortening, such as Duchenne muscular dystrophy – an inherited neuromuscular condition estimated to affect 1 in 3,600 male infants in the US.
Study co-author Helen Blau adds:
“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life. This greatly increases the number of cells available for studies such as drug testing or disease modeling.
One day it may be possible to target muscle stem cells in a patient with Duchenne muscular dystrophy, for example, to extend their telomeres. There are also implications for treating conditions of aging, such as diabetes and heart disease. This has really opened the doors to consider all types of potential uses of this therapy.”
The researchers now plan to investigate how modified TERT mRNA affects other types of human cells.
In June last year, Medical News Today reported on a study led by the University of California-San Francisco, in which researchers claim – contrary to other studies – longer telomeres are associated with an increased risk of brain cancer.