Research Roundup: New Insight into Zombie Cells - a Culprit in Aging


Aging is peculiar. Why do we age? Partly because each time a cell divides, the telomeres of chromosomes — the endcaps that keep the chromosomes from unraveling — get slightly shorter. But another big factor is that cells become senescent, where they don't die but don't really divide, either. Why that happens isn't well understood, but researchers have now identified the mechanism behind how those cells become zombified. For that and more research news, continue reading.

How Zombie Cells Come into Being

Senescent cells, also called zombie cells because it sounds much cooler, are cells that can no longer divide. They accumulate with age and are associated with numerous age-related diseases, including cancer, dementia and cardiovascular disease. A research team with the University of Pittsburgh and UPMC Hillman Cancer Center have identified a mechanism behind how these zombie cells develop. They found that oxidative damage to telomeres, the end caps of chromosomes, can trigger senescence. They published the work in the journal Nature Structural & Molecular Biology.

"Zombie cells are still alive, but they can't divide, so they don't help replenish tissues," Patricia Opresko, Ph.D., professor of environmental and occupational health and of pharmacology and chemical biology at Pitt, as well as senior author of the study, said. "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?"

Each time a cell divides, the telomeres get a tiny bit shorter, which is related to longevity. It was unknown if a cell could divide so often over an individual's lifespan that the telomeres erode completely, with the resulting transition to a zombie cell. They identified a new mechanism for inducing senescent cells that is entirely dependent upon telomeres, which also resolved the issue of why dysfunctional telomeres are not always shorter than functional telomeres. Various factors can generate reactive oxygen molecules that damage DNA, including sunlight, alcohol, smoking, and poor diet. Cells have mechanisms to repair damage to the DNA, but telomeres appear to be particularly sensitive to oxidative damage. The researchers say now that this mechanism is understood, they can begin to test ways to prevent senescence and protect telomeres from oxidative damage.

The Mechanism Behind a Tick-Related Meat Allergy

As if the risk of Lyme disease from a tick bite wasn't bad enough, some tick bites cause a life-threatening meat allergy. Researchers with the Garvan Institute of Medical Research have identified the genetic and molecular structure of key molecules associated with this peculiar disorder. They describe how antibodies interact with the sugar molecule galactose-alpha-1,3-galactose, which all mammals produce except humans and higher primates. When humans are exposed to alpha-gal via bites of a certain tick species, such as Ixodes holocyclus, the immune system flags it as harmful and causes an allergic response. A Particular antibody type, 3-7, holds a natural pocket that alpha-gal can fit into. The researchers say humans appear genetically predisposed to being sensitive to this sugar. The tick I. holocyclus is endemic to Eastern Australia. More than 1,800 cases have the mammalian-meat allergy in Sydney, Australia's northern region, with the highest prevalence worldwide.

Migraine Drugs May Help with Weight Loss

Researchers at the University of Texas Southwestern Medical Center found that triptan-based drugs, commonly used to treat migraine, may be helpful in treating obesity. In working with obese mice, they found that a daily dose of triptan caused them to eat less food and lose weight over a month. Fifteen different serotonin receptors may be involved in appetite, and specific drugs, such as fen-phen and Belviq (lorcaserin), target specific serotonin receptors but have been withdrawn from the market over side effects. But triptans target the serotonin 1B receptor (Htr1b), which has not been well studied in appetite and weight loss. But triptans are well understood from a safety perspective. Their research evaluated six prescription triptans in obese mice fed a high-fat diet for seven weeks. Mice who were given four of the six drugs ate less.

AI Model Can Detect Vaccine Attitudes in Tweets

Artificial Intelligence (AI) developed by the University of Warwick can identify social media users' attitudes about vaccinations. The AI is called the Vaccine Attitude Detection (VADet) Model and is trained first on a small number of sample tweets with attitudes pre-identified by the research team before carrying out larger analyses. The AI then analyzed 1.9 million tweets and could identify Twitter users' stances on aspects related to vaccination, such as safety, side effects, immunity level, conspiracy beliefs and others. In some ways, it doesn't seem that complicated: if a post mentions mistrust of healthcare institutions, a fear of needles, or any known conspiracy theories, the model recognizes the person will be negative toward vaccinations. The authors note that the World Health Organization identified vaccine hesitancy as one of the top 10 health threats to the world in 2019.

Machine Learning Model to Diagnose Alzheimer's and Dementia?

Investigators at Boston University have developed a computer program that leverages a machine-learning computation model to diagnose Alzheimer's disease and dementia. The program can detect cognitive impairment from audio recordings of neuropsychological tests. They trained the program using audio recordings of neuropsychological interviews of more than 1,000 people in the Framingham Heart Study. Utilizing automated online speech recognition tools and a machine learning technique known as natural language processing, the program transcribed the interviews, then encoded them into numbers. A final model evaluated the likelihood and severity of a person's cognitive impairment using demographic data, text encodings, and real diagnoses from neurologists and neuropsychologists. The model accurately differentiated between healthy people and those with dementia. It was also able to detect differences between people with mild cognitive impairment and dementia. They also found that the quality of the recordings and how people spoke were less important than the content.

"It surprised us that speech flow or other audio features are not that critical; you can automatically transcribe interviews reasonably well, and rely on text analysis through AI to assess cognitive impairment," Ioannis Paschalidis, Ph.D., co-author of the study and a BU College of Engineering Distinguished Professor of Engineering, said."

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