Aging Is Reversible
At Least in Human Cells and Live Mice.
New research suggests it is possible to slow or even reverse aging, at least in mice, by undoing changes in gene activity—the same kinds of changes that are caused by decades of life in humans.
By tweaking genes that turn adult cells back into embryoniclike ones, researchers at the Salk Institute for Biological Studies reversed the aging of mouse and human cells in vitro, extended the life of a mouse with an accelerated-aging condition and successfully promoted recovery from an injury in a middle-aged mouse, according to a study published Thursday in Cell.
The study adds weight to the scientific argument that aging is largely a process of so-called epigenetic changes, alterations that make genes more active or less so. Over the course of life cell-activity regulators get added to or removed from genes. In humans those changes can be caused by smoking, pollution or other environmental factors—which dial the genes’ activities up or down. As these changes accumulate, our muscles weaken, our minds slow down and we become more vulnerable to diseases.
The new study suggests the possibility of reversing at least some of these changes, a process researchers think they may eventually get to work in living humans. “Aging is something plastic that we can manipulate,” says Juan Carlos Izpisua Belmonte, the study’s senior author and an expert in gene expression at Salk. In their study Belmonte and his colleagues rejuvenated cells by turning on, for a short period of time, four genes that have the capacity to convert adult cells back into an embryoniclike state.
In living mice they activated the four genes (known as “Yamanaka factors,” for researcher Shinya Yamanaka, the Nobelist who discovered their combined potential in 2006). This approach rejuvenated damaged muscles and the pancreas in a middle-aged mouse, and extended by 30 percent the life span of a mouse with a genetic mutation responsible for Hutchinson–Gilford progeria syndrome, which causes rapid aging in children.
Because the Yamanaka factors reverse changes made to gene regulators, some scientists see the study as further evidence that aging is driven by epigenetic changes. “I do think that epigenetic reprogramming is the ultimate way to reverse aging,” says David Sinclair, a Harvard University geneticist and anti-aging researcher who was not involved in the study but is doing similar work. “My lab has a lot of evidence that the primary driver of what we call the hallmarks of aging is the epigenetic change.” Sinclair says his lab is preparing a paper explaining what causes these changes as we age.
The Salk study was conducted on middle-aged mice. But in theory, reprogramming epigenetics should work on mice and people at any age, says first author Alejandro Ocampo, adding that even cells from human centenarians could eventually be rejuvenated. He and Belmonte say they think they can improve the efficiency and results of the technique with more research—and that they can undo the epigenetic changes responsible for aging by using easier-to-handle chemicals instead of the Yamanaka factors, hopefully moving toward the possibility of treatment for people.
Matt Kaeberlein, a molecular biologist at the University of Washington who studies aging but was not part of the work, says other researchers have found that the Yamanaka factors can rejuvenate cells—so in some ways this study is not surprising. But Kaeberlein says no one else had yet shown that the factors can treat age-related diseases in an animal by making the same changes. “That’s the wow factor,” he explains.
Kaeberlein says the study suggests it may be possible not just to slow aging but to actually reverse it. “That’s really exciting—that means that even in elderly people it may be possible to restore youthful function,” he says. Plus, it is easier to imagine a treatment that makes changes to the epigenome than to consider going into every cell and changing its genes. He also notes that the results of the new study are very similar to those seen when senescent cells—those that have lost function due to aging—are removed from an organism. It is not yet clear, he says, whether “this is another way to shut down or maybe reprogram senescent cells.”
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