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Oxidative Stress Shortens Telomeres

Friday, May 31, 2019


Thank you Buck Institute for Research on Aging for getting this EurekAlert information out shortly after publication: 


A new study from the University of Pittsburgh, published May 14, 2019 in Molecular Cell, provides the first smoking gun evidence that oxidative stress acts directly on telomeres to hasten cellular aging.


The same sources thought to inflict oxidative stress on cells--pollution, diesel exhaust, smoking and obesity--also are associated with shorter telomeres, the protective tips on the ends of the chromosomal shoelace.


"Telomeres consist of hundreds of guanine bases, which are sinks for oxidation," said senior author Patricia Opresko, Ph.D., professor of environmental and occupational health at the Pitt Graduate School of Public Health and UPMC Hillman Cancer Center. "Is it just a coincidence? Or could it be true that oxidizing those guanines in the telomeres is really contributing to shortening?"


To find out for sure, Opresko needed some way to inflict oxidative stress on telomeres and nowhere else.


So, she enlisted the help of Marcel Bruchez, Ph.D., professor of biological sciences and chemistry and director of the Molecular Biosensors and Imaging Center at Carnegie Mellon University. 


Bruchez developed a method for zeroing in on the telomeres using a special light-activated molecule that latches onto the telomere and delivers localized free radicals--the molecular agent of oxidative stress--on command.


"One of the main challenges to targeting oxidative damage to specific loci in living cells has been achieving precise temporal and dose control of this damage," Bruchez said. "By combining telomere targeting with our optochemogenetic generation of singlet oxygen, we are able to selectively control when and how hard the oxidative stress is applied specifically at the telomere sites."


The researchers repeatedly exposed cultured cancer cells to this targeted oxidation procedure, mimicking conditions of environmental oxidative stress and inflammation,  and, indeed, they saw the telomeres break and shorten with each cell division, despite repair efforts by the telomere lengthening enzyme telomerase.


As the DNA repair machinery tried to fix the broken telomeres, the ends of the chromosomes often fused together, destabilizing the genome and preventing cells from dividing properly.


"Whereas telomere shortening spells bad news for healthy cells," Opresko said,  "the flipside is that targeting telomeres might offer a way to fight cancer. With short enough telomeres, cancer cells would stop dividing."


Opresko also said, "If we can understand what causes telomere shortening and how cells compensate for that, then we'll be in a better position to design intervention strategies that protect telomeres in healthy cells and target telomeres in cancer cells."


Ellen Troyer and the Biosyntrx staff


PEARL

If you are looking for another reason to demand cleaner air, telomeres show that environmental stressors can directly shorten the protective tips on chromosomes. Support clean energy and do your best to maintain adequate daily levels of the antioxidant micronutrients that address free radical damage all over the body, including telomeres.