Researchers have found a new pathway for the buildup of “zombie cells,” which promote aging.
Senescent cells, or cells that have lost their ability to divide, increase with age and are major contributors to age-related illnesses such as cancer, dementia, and cardiovascular disease. In a new study, a team led by the University of Pittsburgh and UPMC Hillman Cancer Center researchers discovered a method through which senescent, or “zombie,” cells develop.
The study, which was recently published in the journal Nature Structural & Molecular Biology, demonstrates for the first time that oxidative damage to telomeres — the protecting tips of chromosomes that behave like plastic caps at the end of a shoelace — can cause cellular senescence. These discoveries might ultimately result in new treatments that promote healthy aging or fight cancer.
“Zombie cells are still alive, but they can’t divide, so they don’t help replenish tissues,” said senior author Patricia Opresko, Ph.D., professor of environmental and occupational health and of pharmacology and chemical biology at Pitt. “Although zombie cells don’t function properly, they’re not couch potatoes — they actively secrete chemicals that promote inflammation and damage neighboring cells. Our study helps answer two big questions: How do senescent cells accumulate with age, and how do telomeres contribute to that?”
When a healthy human cell divides to create two identical cells, a little bit of
This hypothesis could not previously be tested since the techniques used to damage DNA were non-specific, creating lesions across the entire chromosome.
“Our new tool is like a molecular sniper,” explained first author Ryan Barnes, Ph.D., a postdoctoral fellow in Opresko’s lab. “It creates oxidative damage exclusively at the telomeres.”
To develop such marksman-like precision, the team used a special protein that binds exclusively to telomeres. This protein acts like a catcher’s mitt, grabbing hold of light-sensitive dye “baseballs” that the researchers tossed into the cell. When activated with light, the dye produces…
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