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Category: genetics – Page 224

A variant of the CTLA-4 gene associated with autoimmune disease was found to be more frequent in non-small cell lung cancer (NSCLC) patients who experienced an exceptionally high response to anti-PD-1 immunotherapy and higher immune-related side effects than in a comparable cohort of lung cancer patients and healthy individuals, according to data presented during the AACR Annual Meeting 2022, held April 8–13.

“Inhibitors of the immune checkpoint proteins PD-1/PD-L1 have transformed the cancer treatment landscape. However, there remains large variability in response and unpredictable adverse events, including autoimmune reactions, in NSCLC patients who undergo this treatment,” said presenter India Allen, BSc, from the Garvan Institute of Medical Research, St Vincent’s Medical School, UNSW, Australia. “There are currently limited biomarkers to effectively predict this variability, and the extent to which a patient’s genetic makeup contributes to response is not well understood.”

The occurrence of immune-related adverse events (irAEs)—the side effects that arise in response to activation of the immune system by immunotherapy—is known to correlate with higher response to anti-PD-1 therapy and improved outcomes in NSCLC patients.

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Our next challenge, then, was to determine the evolutionary connections between these genes. The more similar the two genes were, the more likely viruses with those genes were closely related. Because these sequences had evolved so long ago (possibly predating the first cell), the genetic signposts indicating where new viruses may have split off from a common ancestor had been lost to time. A form of artificial intelligence called machine learning, however, allowed us to systematically organize these sequences and detect differences more objectively than if the task were done manually.

We identified a total of 5,504 new marine RNA viruses and doubled the number of known RNA virus phyla from five to 10. Mapping these new sequences geographically revealed that two of the new phyla were particularly abundant across vast oceanic regions, with regional preferences in either temperate and tropical waters (the Taraviricota, named after the Tara Oceans expeditions) or the Arctic Ocean (the Arctiviricota).

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We produce more than 380 million tonnes of plastic every year, with over 8 million tons of plastic waste escaping into our oceans. Scientists have come up with a creative solution to address this growing plastic problem, and the best thing is that their solution smells and tastes divine.

By getting help from a genetically modified bacteria, a team of researchers at the University of Edinburgh was able to turn plastic bottles into vanilla flavoring. This is the first time a valuable chemical has been achieved from plastic waste.

The study, published in the journal Green Chemistry, explains how bacteria may be used to transform plastic into vanillin, a compound that is used not just in food, but also in cosmetics and pharmaceuticals.

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An analysis of the genetic material in the ocean has identified thousands of previously unknown RNA viruses and doubled the number of phyla, or biological groups, of viruses thought to exist, according to a new study our team of researchers has published in the journal Science.

RNA viruses are best known for the diseases they cause in people, ranging from the common cold to COVID-19. They also infect plants and animals important to people.

These viruses carry their genetic information in RNA, rather than DNA. RNA viruses evolve at much quicker rates than DNA viruses do. While scientists have cataloged hundreds of thousands of DNA viruses in their natural ecosystems, RNA viruses have been relatively unstudied.

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The researchers looked at multiple measures of cellular age. First, they used the epigenetic clock, where chemical tags throughout the genome indicate age. Secondly, they looked at the transcriptome, all the gene readouts produced by the cell. By these two measures, the reprogrammed cells matched the profile of cells that were 30 years younger, compared to reference data sets. In other words, cells from a woman of 53 now appeared like those of a woman aged 23.

The potential applications of this technique are dependent on cells not only appearing younger, but functioning like young cells too. Fibroblasts produce collagen – a molecule found in bones, skin tendons, and ligaments, helping provide structure to tissues and heal wounds. In this study, the rejuvenated fibroblasts produced more collagen proteins compared to control cells that did not undergo the reprogramming process. Fibroblasts also move into areas that need repairing. Researchers tested the partially rejuvenated cells by creating an artificial cut in a layer of cells in a dish, seen in the video below. The treated fibroblasts moved into the gap faster than older cells. This is a promising sign that one day this research could eventually be used to create cells that are better at healing wounds.

In the future, this research may also open up other therapeutic possibilities; the researchers observed that their method also influenced other genes linked to age-related diseases and symptoms. The APBA2 gene – associated with Alzheimer’s, and the MAF gene with a role in the development of cataracts – both showed changes towards youthful levels of transcription.

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Findings could lead to targeted approach for treating aging.

Research from the Babraham Institute has developed a method to ‘time jump’ human skin cells by 30 years, turning back the aging clock for cells without losing their specialized function. Work by researchers in the Institute’s Epigenetics research program has been able to partly restore the function of older cells, as well as rejuvenating the molecular measures of biological age. The research is published today (April 7, 2022) in the journal eLife and whilst at an early stage of exploration, it could revolutionize regenerative medicine.

What is regenerative medicine?

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At roughly 70 years human age, the mice looked elderly and unremarkable. Yet hidden underneath was a youthful cellular clock, turned back in time based on a Nobel-Prize-winning strategy. It’s also the latest bet for finding the fountain of youth, backed by heavy-hitter anti-aging startups in Silicon Valley.

At the center is partial cellular reprogramming. The technique, a sort of gene therapy, forces cells to make four proteins, collectively dubbed the Yamanaka factors. Like erasers, the factors wipe a cell’s genetic history clean, reverting adult cells—for example, skin cells—to a stem cell-like identity, giving them back the superpower to turn into almost any type of cell.

The process isn’t all-or-nothing. In a twist, scientists recently found that they can use the factors to rewind a cell’s genetic history tape rather than destroying it altogether. And if they stop at the right point, the cell dramatically loses its age, becoming more youthful but retaining its identity. The results spurred a wave of interest in moving the therapy to humans, with Calico Life Sciences—a sister company to Google—and Altos Labs, backed by Jeff Bezos, in the race.

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Summary: 15 newly discovered “hotspots” in the genome that either speed up or slow down brain aging could be new targets for the development of Alzheimer’s medications and therapies for other brain disorders.

Source: USC

Researchers from a USC-led consortium have discovered 15 “hotspots” in the genome that either speed up brain aging or slow it down—a finding that could provide new drug targets to resist Alzheimer’s disease and other degenerative brain disorders, as well as developmental delays.

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The only way life extension would remain financially out of reach is if we vote ourselves into a dystopia.

Dr David Sinclair explains why aging therapies will be eventually affordable to us in this clip.

David Sinclair is a professor in the Department of Genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, where he and his colleagues study sirtuins—protein-modifying enzymes that respond to changing NAD+ levels and to caloric restriction—as well as chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, cancer, and cellular reprogramming.

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