The prospect of medical therapies that rewind the clock on the ageing process has edged a little closer after scientists safely rejuvenated tissues in middle-aged mice.
Researchers in the US treated healthy animals with a form of gene therapy that refreshed older cells, making the animals more youthful according to biological markers that are used to measure the effects of ageing.
Repeating the trick in humans is far from straightforward, but the findings will fuel interest in radical new therapies that aim to slow or reverse the ageing process as a means of tackling age-related diseases such as cancer, brittle bones and Alzheimer’s.
“A host of age-related diseases might benefit from this approach,” said Heinrich Jasper, a principal fellow and director at the US biotech firm Genentech.
If the approach can be shown to combat certain health problems, “it would constitute a new therapeutic approach with a significant impact on unmet medical needs at all stages of our life”, he added.
The scientists drew on previous work by the Japanese Nobel laureate Prof Shinya Yamanaka, who showed that a mixture of four molecules – known as Yamanaka factors – can rewind adult cells into youthful stem cells that are capable of forming almost any tissue in the body.
Writing in the journal Nature Aging, the US team led by Jasper and Prof Juan Carlos Izpisua Belmonte at the Salk Institute in California and the San Diego Altos Institute, found that mice who received Yamanaka factors for several months resembled younger animals in many ways, with their skin and kidneys in particular showing signs of rejuvenation.
The experiments showed that rejuvenation was more effective when the therapy was given for a long time – seven to 10 months – starting when the animals were 12 to 15 months old, equivalent to age 35 to 50 in humans. When older animals, equivalent to 80 years old in human terms, were treated for one month, the scientists saw little impact.
Researchers are cautious about using Yamanaka factors in humans because previous work has shown that fully reprogrammed cells can turn into clumps of cancerous tissue called teratomas.
The latest study shows that partial reprogramming may be able to rejuvenate tissues without such risks, but further hurdles remain. Rather than using Yamanaka factors to rejuvenate aged humans, many scientists suspect that new drugs will be needed to partially reprogram cells safely and effectively.
“Will this ever find application in humans?” said Dr Tamir Chandra, an expert in the biology of ageing at the University of Edinburgh, who was not involved in the study.
“In theory, biological age reversal or reduction could be possible. However, we are at very early stages where we need to understand the basic science behind it much better.
“Using Yamanaka factors bears the risk of inducing cancer, and unlike mice, humans – due to their lifespan – carry many more mutations at older age, which might already be predisposed to developing into a cancer.
“Research groups are working on timing, dosage and combinations of Yamanaka factors to minimise this risk.
“Now that we know that loss of cell identity and age reversal can be distinct in their trajectories, other groups are trying to find new factors that uncouple the loss of cell identity from the rejuvenation effects.
“The first applications will likely be in tissue that is easily accessible and can be modified outside the body, like blood stem cells.”