
Low-frequency ultrasound appears to have rejuvenating effects on animals. As well as restarting cell division in ageing human cells, it has reinvigorated old mice, improving their physical performance in tests such as running on a treadmill and making one old mouse with a hunched back move around normally again.
“‘Is this too good to be true?’ is the question I often ask,” says at the University of Texas Medical Branch, whose team is planning to start a small trial in people to see if the technique is safe and can help treat age-related diseases. “We’re examining all aspects of it to see if it really does work.”
After a certain number of divisions – known as the Hayflick limit – the cells in our bodies stop dividing, becoming senescent. Stresses such as toxic chemicals can also make cells become senescent.
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This can have knock-on effects because some senescent cells secrete chemicals that cause inflammation or induce senescence in other cells. The growing proportion of senescent cells in various tissues in our bodies as we get older is thought to be one of the main causes of ageing and age-related diseases. For this reason, many people are that involve killing off senescent cells.
But another approach could be to use low-frequency ultrasound to rejuvenate them.
Sheetz’s team has found that low-frequency ultrasound makes senescent cells from monkeys and humans resume dividing and halts the secretion of chemicals that promote senescence. The researchers used ultrasound with a frequency of less than 100 kilohertz, well below the 2000 kHz or so used for medical imaging.
Human foreskin cells usually show signs of senescence after about 15 divisions, for instance, but with ultrasound treatment reached 24 divisions with no signs of abnormalities. The team is continuing the experiment to see what the limits are.
Extending the Hayflick limit could be useful for growing cells for research or for treating people. Sheetz plans to start selling ultrasound devices to other labs so they can try this.
His team also treated entire animals by placing mice aged between 22 and 25 months in warm water deep enough to cover at least half of their bodies, because ultrasound waves lose less power travelling through water than they do through air. Mice treated with ultrasound improved in physical tests compared with mice that were put in the warm water but weren’t given ultrasound.
In some cases, improvements were dramatic, says Sheetz. One old mouse had a hunched back and wasn’t moving well, and it did the worst in the initial tests. “We treated it twice with ultrasound and it was back to behaving normally,” he says. “I don’t think that rejuvenation is too strong a term.”
The team also used fluorescent dyes that bind to senescent cells to show that the proportion of these cells in the kidneys and pancreas of mice decreased after the treatment.
Why ultrasound has these effects isn’t clear. “Aspects of this are still mystifying,” says Sheetz.
However, his hypothesis is that the physical distortion of cells by ultrasound has effects similar to that of exercise. In particular, it may be reactivating the waste disposal systems inside cells, which grind to a halt in senescent cells.
Are the findings convincing? “Generally, yes,” says at the University of Queensland in Australia. “But I think more work is needed to define the effective ultrasound parameters.” It will also be difficult to apply to people, he says, given that bones and lungs block ultrasound transmission.
Götz’s team has found that mice given a higher-frequency of ultrasound , and a small trial is under way to see if this .
Ultrasound has, for decades, been used as a therapy for a wide range of conditions, but typically treatments used hand-held devices and higher frequencies of ultrasound than Sheetz and his team’s approach. The results have been mixed. The use of different equipment and methods is a major problem in assessing efficacy, say Goetz, as it makes it very hard to compare studies.
Sheetz and his team are planning a trial involving people with osteoarthritis, who will immerse their bodies in water to be treated, and people with diabetic foot ulcers, who will be treated using foot baths. Any therapy that boosts cell division could theoretically increase the risk of cancer, but Sheetz says his team has seen no sign of this.
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