Age related changes like wrinkles, muscle wasting and cataracts could be delayed in mice, say researchers in the US. They achieved the feat by removing old cells that had stopped dividing. These accumulate naturally with age. The scientists believe their findings could eventually “really have an impact” in the care of the elderly. Experts said the results were “fascinating”, but should be taken with a bit of caution.
The study, published in Nature, focused on what are known as “senescent cells”. They stop dividing into new cells and have an important role in preventing tumors from progressing. These cells are cleared out by the immune system, but their numbers build up with time. The researchers estimated that around 10% of cells are senescent in very old people. Slowed-down cells didn’t simply die. If they did, tissues would flush them out. Instead they linger, oozing inflammatory proteins and other cellular pollutants. Many researchers think senescence-related tissue dysfunction contributes to heart disease and cancer and other conditions that become more likely with age.
Scientists at the Mayo Clinic, in the US, devised a way to kill all senescent cells in genetically engineered mice. The animals would age far more quickly than normal, and when they were given a drug, the senescent cells would die.
The researchers looked at three symptoms of old age: formation of cataracts in the eye; the wasting away of muscle tissue; and the loss of fat deposits under the skin, which keep it smooth. Researchers said the onset of these symptoms was “dramatically delayed” when the animals were treated with the drug.
When it was given after the mice had been allowed to age, there was an improvement in muscle function. One of the researchers, Dr James Kirkland, said, “I've never seen anything quite like it.” His colleague Dr Jan van Deursen added, “We were very surprised by the very profound effect. I really think this is very significant.” “Their healthspan was extended,” said gerontologist Darren Baker of the Mayo Clinic. “They were healthier until the time they died.”
However, senescent cells cannot be just flushed out of human beings. Dr Deursen said, “I'm very optimistic that this could really have an impact. Nobody wants to live longer if the quality of life is poor.”
He explained that young people were already clearing out their senescent cells. “If you can prime the immune system, boost it a little bit, to make sure senescent cells are removed, that might be all it needs. Or develop a drug that targets senescent cells because of the unique proteins the cells make.”
Dr Jesus Gil, from the Medical Research Council's Clinical Sciences Centre, said the findings needed to be “taken with a bit of caution. It is a preliminary study”. However, he said it was a fascinating study which “suggests if you get rid of senescent cells you can improve phenotypes [physical traits] associated with ageing and improve quality of life in aged humans”.
“The bottom-line question is, what happens when you increase or decrease cellular senescence in an animal? That’s where this comes in, and that’s why it’s so important,” said Felipe Sierra, director of the National Institute on Aging’s Division of Aging Biology, which helped fund the research. However, Sierra advised caution: Intervening in a mouse model of disease, maintained in pathogen-free settings, is far easier than treating healthy mice. Other, as-yet-unanticipated effects could still emerge. Sierra described the findings as “low-hanging fruit.”
Their cautions were seconded by gerontologist Steven Austad of the University of Texas, who was not involved in the study. He noted that many mouse-level successes prove far more complicated than they initially seem. Most recently, a much-hyped longevity drug target fell into disrepute after new studies failed to support its early promise.
“The most interesting thing is not the effect that knocking out senescent cells had on this animal, but the demonstration that there’s a technology we could use to knock out senescent cells in specific tissues,” said Austad. “Now we’ve got a technique to do this, and it sets the stage for really big stuff in the future. This has the potential to answer a really big question that has bedeviled the field for a long time: How important is cellular senescence for whole-animal senescence?” “This area has been developing for the last 50 years,” said Sierra. “It’s getting extremely exciting.”
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