Researchers uncover key mechanisms of cancer, aging and inflammation

November 7, 2016
Human chromosomes (grey) capped by telomeres (white). Credit: PD-NASA; PD-USGOV-NASA

A team of University of Pittsburgh researchers has uncovered new details about the biology of telomeres, "caps" of DNA that protect the tips of chromosomes and play key roles in a number of health conditions, including cancer, inflammation and aging. The new findings were published today in the journal Nature Structural and Molecular Biology.

Telomeres, composed of repeated sequences of DNA, are shortened every time a cell divides and therefore become smaller as a person ages. When they become too short, send a signal to the cell to stop dividing permanently, which impairs the ability of tissues to regenerate and contributes to many aging-related diseases, explained lead study author Patricia Opresko, Ph.D., associate professor of Environmental and Occupational Health at Pitt, and member of the University of Pittsburgh Cancer Institute Molecular and Cellular Cancer Biology program and Carnegie Mellon University Center for Nucleic Acids Science and Technology.

In contrast, in most cancer cells, levels of the enzyme telomerase, which lengthens telomeres, are elevated, allowing them to divide indefinitely.

"The new information will be useful in designing new therapies to preserve telomeres in healthy cells and ultimately help combat the effects of inflammation and aging. On the flip side, we hope to develop mechanisms to selectively deplete telomeres in cancer cells to stop them from dividing," said Dr. Opresko.

A number of studies have shown that —a condition where damaging molecules known as build up inside cell—accelerates telomere shortening. Free radicals can damage not only the DNA that make up telomeres, but also the DNA building blocks used to extend them.

Oxidative stress is known to play a role in many , including inflammation and cancer. Damage from free radicals, which can be generated by inflammation in the body as well as environmental factors, is thought to build up throughout the aging process.

The goal of the new study was to determine what happens to telomeres when they are damaged by oxidative stress. The researchers suspected that oxidative damage would render telomerase unable to do its job.

"Much to our surprise, telomerase could lengthen telomeres with oxidative damage," Dr. Opresko said. "In fact, the damage seems to promote telomere lengthening."

Next, the team looked to see what would happen if the building blocks used to make up telomeres were instead subjected to oxidative damage. They found that telomerase was able to add a damaged DNA precursor molecule to the end of the telomere, but was then unable to add additional DNA molecules.

The new results suggest that the mechanism by which oxidative stress accelerates telomere shortening is by damaging the DNA precursor molecules, not the telomere itself. "We also found that oxidation of the DNA building blocks is a new way to inhibit telomerase activity, which is important because it could potentially be used to treat cancer."

Dr. Opresko and her team are now beginning to further explore the consequences of oxidative stress on telomeres, using a novel photosensitizer, developed by Marcel Bruchez at Carnegie Mellon University that produces selectively in telomeres. "Using this exciting new technology, we'll be able to learn a lot about what happens to telomeres when they are damaged, and how that damage is processed," she said.

Explore further: First glimpse of end-of chromosome repair in real time

More information: Oxidative guanine base damage regulates human telomerase activity, Nature Structural and Molecular Biology, nature.com/articles/doi:10.1038/nsmb.3319

Related Stories

First glimpse of end-of chromosome repair in real time

October 19, 2016
Researchers have developed a first-of-its- kind system to observe repair to broken DNA in newly synthesized telomeres, an effort which has implications for designing new cancer drugs.

Ultra short telomeres linked to osteoarthritis

January 16, 2012
Telomeres, the very ends of chromosomes, become shorter as we age. When a cell divides it first duplicates its DNA and, because the DNA replication machinery fails to get all the way to the end, with each successive cell ...

TERRA, the RNAs that protect telomeres

August 17, 2016
Despite their especially compact and inaccessible structure, telomeres transcribe information like the rest of the DNA. The RNAs resulting from this process are called TERRA, and their function is essential in preserving ...

Weight loss from bariatric surgery appears to reverse premature aging

July 8, 2016
Weight loss from bariatric surgery appears to reverse the premature aging associated with obesity, according to research presented today at Frontiers in CardioVascular Biology (FCVB) 2016.1 Patients had longer telomeres and ...

New method detects telomere length for research into cancer, aging

June 29, 2016
UT Southwestern Medical Center cell biologists have identified a new method for determining the length of telomeres, the endcaps of chromosomes, which can influence cancer progression and aging.

For older men, short telomeres can be a sign of chronic stress

March 11, 2014
(Medical Xpress)—Andrew Steptoe of University College London and his colleagues have found that telomere length can predict how long it takes older men to recover from stressful situations. Men with shorter telomeres have ...

Recommended for you

Researchers find way to convert bad body fat into good fat

September 19, 2017
There's good fat and bad fat in our bodies. The good fat helps burn calories, while the bad fat hoards calories, contributing to weight gain and obesity. Now, new research at Washington University School of Medicine in St. ...

Cell-based therapy success could be boosted by new antioxidant

September 19, 2017
Cell therapies being developed to treat a range of conditions could be improved by a chemical compound that aids their survival, research suggests.

New model may help science overcome the brain's fortress-like barrier

September 19, 2017
Scientists have helped provide a way to better understand how to enable drugs to enter the brain and how cancer cells make it past the blood brain barrier.

Study suggests epilepsy drug can be used to treat form of dwarfism

September 19, 2017
A drug used to treat conditions such as epilepsy has been shown in lab tests at The University of Manchester to significantly improve bone growth impaired by a form of dwarfism.

Research predicts how patients are likely to respond to DNA drugs

September 19, 2017
Research carried out by academics at Northumbria University, Newcastle could lead to improvements in treating patients with diseases caused by mutations in genes, such as cancer, cystic fibrosis and potentially up to 6,000 ...

Urine output to disease: Study sheds light on the importance of hormone quality control

September 18, 2017
The discovery of a puddle of mouse urine seems like a strange scientific "eureka" moment.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Dug
1 / 5 (1) Nov 07, 2016
Unfortunately, this only helps slow aging symptoms. It doesn't extend maximum longevity and it doesn't put us any closer to have control over the genetic default aging codes that cause us age to start with.
jhnycmltly
not rated yet Dec 06, 2016
No mention of Linus Pauling and now since he has already 'done the leg work' we can immediately 'get to work' with natural substances which have been proven to work against oxidative stress, one of which is the chaff of your grain, phytate, a naturally occurring iron binder which effectively binds up excess iron which is present due to a herbivore species, humans, eating meat.
"Herbivore Hypothesis"

"Higher iron levels associated with increased risk of gestational diabetes in pregnant women"

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.