Researchers have returned stem cells from older donors to a more youthful biological state.
In a new study, published in Nature Communications, stem cells from a group of 60-90-year-old donors were grown in the lab and briefly treated with a specific mixture of factors, which 'reset' their biological age. The researchers found that the rejuvenated cells behaved like cells between 1.5-7.5 years younger than untreated cells in terms of their epigenetic signature. They also saw dramatic improvements in their metabolism, nutrient sensing and waste removal pathways.
'We are very excited about these findings,' said Professor Thomas Rando from Stanford University, California, a co-author on the study. 'My colleagues and I have been pursuing the rejuvenation of tissues since our studies in the early 2000s revealed that systemic factors can make old tissues younger.'
Multiple different types of stem cells - including skin, muscle, and blood vessel cells - were treated with a cocktail of proteins known as 'Yamanaka' factors, which are typically used to transform adult stem cells into induced pluripotent stem cells (iPSCs). These are 'embryonic'-like cells, which can form any type of tissue in the body. Instead of a prolonged treatment with Yamanaka factors, as is necessary for making iPSCs, the cells were only exposed briefly, rejuvenating them rather than erasing their identify.
'When iPS cells are made from adult cells, they become both youthful and pluripotent,' said Dr Vittorio Sebastiano, assistant professor of obstetrics and gynaecology at Stanford and senior author on the study. 'We've wondered for some time if it might be possible to simply rewind the ageing clock without inducing pluripotency. Now we've found that, by tightly controlling the duration of the exposure to these protein factors, we can promote rejuvenation in multiple human cell types.'
The study was extended to mouse muscle stem cells, in which similar rejuvenating effects were seen. The researchers also transplanted rejuvenated muscle cells into elderly mice and found that they regained strength.
The researchers also harvested cartilage cells from patients with osteoarthritis and found that after a low dosage of Yamanaka factors these cells reduced secretion of the inflammatory factors that provoke the disease, and improved their ability to function.
Several of the study authors, including Dr Sebastiano, have co-founded a company, Turn Biotechnologies, to develop treatments based on their research. 'Although much more work needs to be done, we are hopeful that we may one day have the opportunity to reboot entire tissues,' said Sebastiano. 'But first we want to make sure that this is rigorously tested in the lab and found to be safe.'
Professor Leonard Guarente, an expert on ageing at Massachusetts Institute of Technology, who was not involved in the study, told the New York Times that the method was 'one of the most promising areas of ageing research 'but that it would take a long time to develop drugs.