Killing off cells that refuse to die on their own has proved to be a powerful anti-aging strategy on mice. Now is it time to test this on humans?
We are sharing information by Megan Scudellari from Nature and the National Institute of Aging because we want our readers to stay informed of the ever growing science of aging on a molecular level. – the HHN Team
When Jan van Deursen noted that the mice he had created were rapidly aging, he discovered a cell that could not divide nor would die. This gave Deursen and his colleagues an idea: could killing off these ‘zombie’ cells delay their aging? The answer was yes.
In a 2011 study, the team found that eliminating these ‘senescent’ cells forestalled many of the ravages of age. The discovery set off a spate of similar findings. In the seven years since, dozens of experiments have confirmed that senescent cells accumulate in aging organs, and that eliminating them can alleviate, or even prevent, certain illnesses. This year alone, clearing the cells in mice has been shown to restore fitness, fur density and kidney function. It has also improved lung disease and even mended damaged cartilage. In a 2016 study, it seemed to extend the lifespan of normally aging mice. As stated from Nature.
“Just by removing senescent cells, you could stimulate new tissue production,” says Jennifer Elisseeff, senior author of the cartilage paper and a biomedical engineer at Johns Hopkins University in Baltimore, Maryland.
This anti-aging phenomenon has been an unexpected twist in the study of senescent cells, a common, non-dividing cell type first described more than five decades ago. When a cell enters senescence — and almost all cells have the potential to do so — it stops producing copies of itself, begins to belch out hundreds of proteins, and cranks up anti-death pathways full blast. A senescent cell is in its twilight: not quite dead, but not dividing as it did at its peak. As stated from Nature.
What is a senescent cell?
Senescent cells are unique in that they eventually stop multiplying but don’t die off when they should. They instead remain and continue to release chemicals that can trigger inflammation. Like the one moldy piece of fruit that corrupts the entire bowl, a relatively small number of senescent cells can persist and spread inflammation that can damage neighboring cells.
However, not all senescent cells are bad. The molecules and compounds expressed by senescent cells (known as the senescent secretome) play important roles across the lifespan, including in embryonic development, childbirth, and wound healing. As stated by the National Institute of Aging.
The Dark Side
In 2008, three research groups, including Campisi’s at the Buck Institute for Research on Aging in Novato, California, revealed that senescent cells excrete a glut of molecules — including cytokines, growth factors and proteases — that affect the function of nearby cells and incite local inflammation. Campisi’s group described this activity as the cell’s senescence associated secretory phenotype, or SASP.
Surprisingly, senescent cells turn out to be slightly different in each tissue. They secrete different cytokines, express different extracellular proteins and use different tactics to avoid death. That incredible variety has made it a challenge for labs to detect and visualize senescent cells. “There is nothing definitive about a senescent cell. Nothing. Period,” says Campisi. From Nature.
In the End
If eliminating senescent cells in humans does improve age-related illnesses, researchers will aim to create broader anti-aging therapies, says David. In the meantime, researchers in the field insist that no one should take these drugs until proper safety tests in humans are complete. In rodents, senolytic compounds have been shown to delay wound healing, and there could be additional side effects. “It’s just too dangerous,” says Kirkland. Van Deursen says that continuing to answer basic biological questions is the field’s best shot at success. “Only then will we be able to understand what aging really is, and how we can, in an intelligent way, interfere with it.” As stated from Nature.