Run-down cells, known as senescent

Run-down cells, known as senescent cells, may make us old. A new study of mice suggests that they also drive another scourge of our advancing years—atherosclerosis, the buildup of fatty plaques in our arteries that can spur heart attacks and strokes. If scientists verify the findings, drugs that cull the cells could one day treat or even prevent one of the world’s biggest killers.

The contribution of senescent cells to atherosclerosis has remained murky, but the new study provides “the best evidence that they are important,” says cardiovascular pathologist Gary Owens of the University of Virginia School of Medicine in Charlottesville, who wasn’t connected to the research.

Senescent cells permanently stop reproducing, but they can linger in the body for a lifetime. Their inability to reproduce is a good thing, scientists say. Because they are stressed out or carry damaged DNA, they could spawn tumors if they continued to divide. Senescence has its downsides, however. As more cells in a tissue senesce, they can’t reproduce to furnish replacements for other cells that have died or been injured. In addition, senescent cells don’t completely shut down; they continue to leak enzymes and other molecules that can alter their environment.

Over the years, these run-down cells accumulate in our bodies, leading researchers to suspect that they are responsible for at least some of the physical decline of old age. Earlier this year, a team led by cancer biologist Jan van Deursen of the Mayo Clinic in Rochester, Minnesota, bolstered that notion, revealing that deleting senescent cells from mice increased their life spans by up to 20% and improved their health.

In their new study, Van Deursen and colleagues tried to determine the role of senescent cells in atherosclerosis. Previous studies have disagreed about the cells’ impact on plaque formation, with some suggesting that they promote it and others indicating that they help prevent it. To tackle the question, Van Deursen and his team used mice that had been genetically engineered to kill off many of their senescent cells in response to a particular drug. The researchers let the mice chow down on a fat-rich diet for 3 months and dosed some of them with the drug.

When the scientists measured the amount of fatty buildup in one of the animals’ major arteries, they found that mice purged of senescent cells carried 60% less plaque than did the other mice. Atherosclerosis developed rapidly in the animals that retained senescent cells. Within just 9 days of starting the high-fat diet, they sported streaks of fat in their arteries that are harbingers of the disease, the researchers report online today in Science. These lesions teemed with senescent cells. In the rodents that received the drug, however, the telltale streaks were much smaller, and harbored few senescent cells. Owens says that the speed at which senescent cells appeared is disturbing. “It makes you worry if you go on a fast food binge for a couple of days,” he says.

Plaques can become lethal if they fracture and trigger blood clots, which can block arteries and lead to a heart attack or stroke. In the mice that eliminated their senescent cells, Van Deursen and colleagues found, plaques carried thicker protective caps and thus were less likely to break. Several types of senescent cells lurk inside plaques, but the researchers’ results suggest that the wrongdoers that promote atherosclerosis are foam cells, a type of immune cell that has settled down in the artery lining and begun feasting on fats. “We think they have roles throughout the process of atherosclerosis,” Van Deursen says. Early on, senescent foam cells may promote the growth of lesions by inciting inflammation. In older lesions, the cells may cause trouble by releasing enzymes that weaken the plaque.

The study marks the first attempt to remove senescent cells from plaques and determine the effects, says vascular biologist Martin Bennett of the University of Cambridge in the United Kingdom, who wasn’t connected to the research. But the molecular markers the scientists used to recognize and remove senescent cells are not exclusive to those cells, he notes. “Thus, they need to be sure that what they have identified or ablated in atherosclerosis are just senescent cells.” Owens agrees that the researchers could have done more to confirm that the cells they targeted are senescent. If they can do that, he says, their technique could pave the way for atherosclerosis treatment. “This would be a whole new approach, and that’s pretty exciting.”

Several groups of researchers have developed so-called senolytic drugs that slay senescent cells, and clinical trials of one compound, developed by a company co-founded by Van Deursen, will start early next year in patients with a type of arthritis. Tests in atherosclerosis patients could be a way off, however. For one thing, Van Deursen says, researchers first need to show that targeting senescent ce

Kết quả (Việt) 1:

Chạy xuống các tế bào, được gọi là tế bào senescent, có thể làm cho chúng ta già. Một nghiên cứu mới của những con chuột cho thấy rằng họ cũng lái xe một thiên tai của chúng tôi năm tiến-xơ vữa động mạch, sự tích tụ các mảng bám mỡ trong động mạch của chúng tôi mà có thể thúc đẩy cơn đau tim và đột quỵ. Nếu các nhà khoa học xác thực những phát hiện, ma túy huỷ các tế bào có thể một ngày điều trị hoặc thậm chí ngăn chặn một kẻ giết người lớn nhất của thế giới.Sự đóng góp của các tế bào senescent đến xơ vữa động mạch vẫn âm u, nhưng nghiên cứu mới cung cấp các "chứng cứ tốt nhất họ là quan trọng," ông nghiên cứu bệnh học tim mạch Gary Owens của đại học Virginia School of Medicine ở Charlottesville, những người đã không được kết nối với các nghiên cứu.Senescent tế bào vĩnh viễn ngừng tái tạo, nhưng họ có thể nán lại trong cơ thể suốt đời. Họ không có khả năng sinh sản là một điều tốt, các nhà khoa học nói. Bởi vì họ đang căng thẳng hoặc mang DNA bị hư hỏng, họ có thể đẻ trứng khối u nếu họ tiếp tục phân chia. Senescence có nhược điểm của nó, Tuy nhiên. Càng nhiều các tế bào trong một mô senesce, họ không thể tái tạo để cung cấp các thay thế cho các tế bào khác mà đã qua đời hoặc bị thương. Ngoài ra, các tế bào senescent hoàn toàn không đóng cửa; họ tiếp tục rò rỉ enzyme và các phân tử khác mà có thể làm thay đổi môi trường của họ.Trong những năm qua, các tế bào này chạy xuống tích tụ trong cơ thể chúng ta, dẫn đầu các nhà nghiên cứu nghi ngờ rằng họ có trách nhiệm ít nhất một số vật chất từ chối của tuổi già. Đầu năm nay, một đội ngũ lãnh đạo bởi nhà sinh học ung thư Jan van Deursen của Mayo Clinic ở Rochester, Minnesota, ủng hộ các khái niệm đó, tiết lộ rằng xoá senescent các tế bào từ chuột tăng kéo dài cuộc sống của họ lên đến 20% và cải thiện sức khỏe của họ.Trong nghiên cứu mới của họ, Van Deursen và các đồng nghiệp đã cố gắng để xác định vai trò của các tế bào senescent trong xơ vữa động mạch. Nghiên cứu trước đây đã không đồng ý về tác động đến các tế bào hình thành mảng bám, với một số gợi ý rằng họ thúc đẩy nó và những người khác chỉ ra rằng họ giúp ngăn chặn nó. Để giải quyết các câu hỏi, Van Deursen và nhóm của ông sử dụng con chuột đã được thiết kế di truyền để giết off nhiều tế bào senescent của họ để đáp ứng với một loại thuốc cụ thể. Các nhà nghiên cứu cho chuột chow trên một chế độ ăn giàu chất béo cho 3 tháng và thoả chúng với ma túy.When the scientists measured the amount of fatty buildup in one of the animals’ major arteries, they found that mice purged of senescent cells carried 60% less plaque than did the other mice. Atherosclerosis developed rapidly in the animals that retained senescent cells. Within just 9 days of starting the high-fat diet, they sported streaks of fat in their arteries that are harbingers of the disease, the researchers report online today in Science. These lesions teemed with senescent cells. In the rodents that received the drug, however, the telltale streaks were much smaller, and harbored few senescent cells. Owens says that the speed at which senescent cells appeared is disturbing. “It makes you worry if you go on a fast food binge for a couple of days,” he says.Plaques can become lethal if they fracture and trigger blood clots, which can block arteries and lead to a heart attack or stroke. In the mice that eliminated their senescent cells, Van Deursen and colleagues found, plaques carried thicker protective caps and thus were less likely to break. Several types of senescent cells lurk inside plaques, but the researchers’ results suggest that the wrongdoers that promote atherosclerosis are foam cells, a type of immune cell that has settled down in the artery lining and begun feasting on fats. “We think they have roles throughout the process of atherosclerosis,” Van Deursen says. Early on, senescent foam cells may promote the growth of lesions by inciting inflammation. In older lesions, the cells may cause trouble by releasing enzymes that weaken the plaque.
The study marks the first attempt to remove senescent cells from plaques and determine the effects, says vascular biologist Martin Bennett of the University of Cambridge in the United Kingdom, who wasn’t connected to the research. But the molecular markers the scientists used to recognize and remove senescent cells are not exclusive to those cells, he notes. “Thus, they need to be sure that what they have identified or ablated in atherosclerosis are just senescent cells.” Owens agrees that the researchers could have done more to confirm that the cells they targeted are senescent. If they can do that, he says, their technique could pave the way for atherosclerosis treatment. “This would be a whole new approach, and that’s pretty exciting.”

Several groups of researchers have developed so-called senolytic drugs that slay senescent cells, and clinical trials of one compound, developed by a company co-founded by Van Deursen, will start early next year in patients with a type of arthritis. Tests in atherosclerosis patients could be a way off, however. For one thing, Van Deursen says, researchers first need to show that targeting senescent ce