Scientists extend telomeres to slow cell aging
Will extending telomeres lead to longer, healthier lives? Researchers have taken an important step toward answering this question by developing a new treatment used in the laboratory that extends telomeres.
One of the key aspects of aging is the shortening of telomeres over time. Telomeres, which serve as protective “end caps” for chromosomes, help keep DNA healthy and functioning as it replicates. Unfortunately, these protective end caps become shorter with each DNA replication, and eventually are no longer able to protect DNA from sustaining damage and mutations. In other words, we get older.
An important step toward lengthening telomeres has now been made, which not only allows scientists to increase cell numbers for testing drugs, but may also hold a key to longer and healthier lives. This research was published online in The FASEB Journal.
“In the near term, since biomedical research depends heavily on having large numbers of cells available for study, we hope that these findings will be broadly applicable in the search for treatments and cures for disease,” said Helen M. Blau, Ph.D., who led the research as Director of the Baxter Laboratory for Stem Cell Biology in the Department of Microbiology and Immunology at Stanford University School of Medicine in Stanford, California, and an Associate Editor of The FASEB Journal, the Bethesda, Maryland-based journal in which her report was published.
“Ultimately, we hope that these findings will help prevent, delay or treat age-related conditions and diseases, as well as certain devastating genetic diseases of inadequate telomere maintenance.”
To make this discovery, Blau and colleagues delivered modified mRNA encoding TERT, the enzyme that increases the length of telomeres by adding DNA repeats, to four groups of cells. The first group received modified mRNA encoding TERT, and the other three groups were controls that received either mRNA encoding an inactive form of TERT, the solution in which TERT is delivered, or no treatment. The telomeres of the first group (telomere-extending treatment group) were rapidly lengthened over a period of a few days, whereas the telomeres of the three control groups were not extended. The first group was also able to undergo more cell divisions, whereas the controls were not. Importantly for the potential safety of this approach, the telomeres of the first group resumed shortening after they were extended, showing that due to the short, transient treatment, the cells were not immortalized.
Further, all of the cell populations treated eventually stopped dividing, indicating that they were not immortalized. This approach has been tested on cell types including fibroblasts and myoblasts and is now being tested on stem cells. Additionally, this research showed that cells could be treated several times with enhanced effects on the capacity for division. Since the increase in numbers is compounded with each treatment, a small sample of cells, for example from a small biopsy, can be amplified to very large numbers.
“We were surprised and pleased at how quickly modified TERT mRNA extends telomeres,” said John Ramunas, first author and postdoctoral fellow who pioneered this work in Blau’s Stanford University laboratory. “In fibroblasts, over a decade of telomere shortening was reversed in a few days, suggesting that a therapy might be brief and infrequent.”
Healthy Habits May Slow Cell Aging, Protect Against Stress
Exercise, a healthy diet and good sleep can protect the body against the negative effects of stress and slow down the aging process at a cellular level, researchers report. The findings are published online July 29 in Molecular Psychiatry.
The researchers followed 239 postmenopausal, nonsmoking women for one year. The women provided blood samples at the beginning and the end of the year for telomere measurement. They underwent periodic reviews of their physical activity, diet, and sleep. At the end, the women also reported on major stress events that occurred during the year.
The researchers found that major stress events caused a significantly greater decline in telomere lengths for women who halfheartedly engaged in healthy behaviors. But the same levels of stress caused no greater shortening in the telomeres of women who stayed active, ate healthily, and slept well.
The study adds to our understanding of how healthy living affects the aging process, lead author Eli Puterman, PhD, assistant professor of psychiatry at the University of California San Francisco School of Medicine, told HealthDay. “The same type of person who eats well and still exercises is the same sort of person who isn’t aging much,” he said. “As we get deeper and deeper into the cell, we’re getting more information about why and what’s happening at the genetic level.”
“It might not be the Fountain of Youth to keep us young forever, but this discovery is a real shot in the arm. This work is a game-changer,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. He added, “in the short term it will help us to understand how aging affects the molecular machinery of cells. In the long-term, the sky’s the limit. Biologists have long guessed that the key to a longer lifespan is figuring out how to extend telomeres. Helen Blau and her colleagues have just done that.”
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How Do Telomeres Affect Aging?
The repetitive stretches of DNA at the ends of chromosomes are called telomeres. They are compared to the plastic tips at the end of shoe laces, since they prevent the chromosomal ends from fusing with neighboring chromosomes. The telomeres keep getting shorter each time the cell divides, and when they become too short the cell can no longer divide and it dies. Telomeres also get shorter with age.
But in this study the researchers proved that a healthy lifestyle that includes physical activity, controled diet, and adequate sleep could reduce telomere shortening and thereby ageing. They did this by examining the effect of these behaviors in 239 post-menopausal, non-smoking women, over the course of one year. The women provided blood samples at the beginning and end of the year, which were checked for telomere measurements.
The women also reported of any stressful events that had occurred in their lives over the course of the year. In women who engaged in lower levels of healthy behaviors, there was a significantly greater decline in telomere length in their immune cells for every major life stressor that occurred during the year. Conversely, women who followed a healthy lifestyle, in spite of experiencing life stressors were found to have lesser shortening.
“This is the first study that supports the idea, at least observationally, that stressful events can accelerate immune cell aging in adults, even in the short period of one year,” Puterman said. “Exciting, though, is that these results further suggest that keeping active, and eating and sleeping well during periods of high stress are particularly important to attenuate the accelerated aging of our immune cells.”
Apart from aging, the shortening length of the telomeres is also associated with cancer of the prostate, bladder, lung, and kidney. These cancer cells also produce more of the enzyme telomerase to prevent shortening of the telomeres and continue growing. So a measure of telomerase can be used to detect cancer.
Other age-related diseases associated with shortening telomeres are stroke, vascular dementia, cardiovascular disease, obesity, and osteoporosis diabetes.
Details: John Ramunas, Eduard Yakubov, Jennifer J. Brady, Stéphane Y. Corbel, Colin Holbrook, Moritz Brandt, Jonathan Stein, Juan G. Santiago, John P. Cooke, and Helen M. Blau. Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells. FASEB J. doi:10.1096/fj.14-259531
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