Through cell reprogramming, the team of researchers led by the UCAM professor managed to rejuvenate mice without generating tumors or any other health problem. The study is published in the scientific journal Nature Aging
Age may become just a number and not be associated with unwanted effects such as brittle bones, muscle weakness, or increased risk of cardiovascular disease or cancer. A team of scientists led by Dr. Izpisua Belmonte demonstrated in research promoted and funded by the UCAM that aging can be reversed safely and effectively, both in elderly and middle-aged mice, by partially reprogramming their cells to more youthful stages .
‘Our results indicate that we can use this method to delay aging in naturally aged animals. The technique is safe and effective in mice”, said Juan Carlos Izpisua Belmonte, professor of Developmental Biology at UCAM and professor at the Gene Expression Laboratory at the Salk Institute, California. “As well as allowing us to address age-related diseases, this approach provides the biomedical community with a new tool to restore the health of aged tissues and the body itself, improving the functioning of cells in different pathological situations, such as , neurodegenerative diseases of the musculoskeletal system, skin or kidney diseases».
As organisms age, not only does their outward appearance and health change; Every cell in the body has a molecular clock that tracks the passage of time. Cells isolated from elderly individuals present epigenetic marks in their DNA, due to lifestyle and interaction with the environment, different from those existing in young individuals. Treating aged cells with a mixture of four cell reprogramming factors (Oct4, Sox2, Klf4, and cMyc), also known as “Yamanaka factors,” can erase these epigenetic marks accumulated over time, such that adult cells can become developmentally into stem cells.
“In 2016, when this project began with the help of Izpisua Belmonte, we published, for the first time, that using Yamanaka factors it was possible to reverse aging and increase the lifespan of mice suffering from progeria (a disease that causes premature aging) . Later, in 2021, in a project developed in collaboration with the Spanish Olympic Committee, we published that, even in young mice, Yamanaka factors can accelerate muscle regeneration; and, based on these publications, other scientific teams have improved the function of other tissues such as the heart, brain and optic nerve”, commented Estrella Núñez, co-author of the work and vice-rector for Research at UCAM.
The study and its conclusions
In the study now published in the journal Nature Aging, Izpisua and his collaborators applied this same rejuvenation technology to healthy animals that age naturally (with age): a group of mice received regular doses of Yamanaka factors from the age of 15 up to 22 months of age, which is approximately equivalent to 50 to 70 years in humans; a second group was treated from 12 to 22 months, from 35 to 70 years in humans; and a third group was treated for only one month at 25 months of age, 80 years in humans.
“What we wanted to check was whether applying Yamanaka factors over a longer period of time is safe and does not lead to tumor formation,” said Pradeep Reddy, co-first author of the new paper. No negative effect was observed in the health, behavior or body weight of the treated animals compared to the control group (untreated). There were also no blood cell abnormalities, neurological changes, or cancer in any of the treated animals.
When the researchers analyzed the signs of aging in the treated animals, they found that in many ways they resembled young animals. The epigenetic patterns of the kidney and skin cells of the treated animals were very similar to those of the younger animals. They found that when skin cells from treated animals were injured, they had a greater ability to proliferate and were less likely to form permanent scars than those from untreated animals.
This rejuvenation was observed in animals treated for seven or ten months with the Yamanaka factors (groups one and two), but not in those treated for only one month (group three). “When the animals were analyzed midway through treatment, the effects were still not as apparent. This suggests that the treatment is not just stopping aging, but actively reversing it, although more research is needed to differentiate the two,” Reddy said.
Currently, the research team is planning new projects to analyze how long-term treatment with Yamanaka factors affects specific molecules and genes, as well as developing new ways to administer these factors. “We want to restore full functionality and recovery capacity to aged cells or cells that have lost their function so that they are more resistant to stress, injury and disease,” said Izpisua Belmonte. “Our results show that, at least in mice, there is a way to achieve this.” The study has been funded by the UCAM and the Dr. Pedro Guillén Foundation.