Eternal life is a utopia, but active and healthy aging while avoiding the physical problems associated with age, such as bone or muscle pathologies, or an increased risk of developing cancer or cardiovascular diseases, could become a reality in the not-too-distant future. far away, since a group of scientists led by Dr. Juan Carlos Izpisua Belmonte has shown in a study with healthy mice that it is possible to reverse the signs of aging, both in elderly animals and in middle-aged animals.
In the research, which has been promoted and financed by the Universidad Católica San Antonio de Murcia (UCAM), they have achieved this milestone – safely and effectively – by partially reprogramming the cells of rodents to more juvenile 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,” says Dr. Izpisua Belmonte, Professor of Developmental Biology at UCAM and professor at the Salk Institute’s Gene Expression Laboratory, California.
“In addition to 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, of the skin or kidney diseases”, adds the scientist.
Erase the traces of the passage of time without side effects
Aging not only alters our outward appearance and deteriorates our health, but each cell in the body has a molecular clock that records the passage of time, and cells isolated from elderly individuals show epigenetic marks in their DNA that are due to their style. of life and their interaction with the environment and that differ from those presented by young individuals. Treating those aged cells with a combination of four cell reprogramming factors (Oct4, Sox2, Klf4 and cMyc), also known as ‘Yamanaka factors’, can erase those epigenetic marks that have accumulated over time so that the adult cells they can become developmentally into stem cells.
“This approach provides a new tool to recover the health of aged tissues and of the body itself, improving the functioning of cells in different pathological situations”
“In 2016, when this project was started by Dr. 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 rapid aging). premature). 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”, explained Estrella Núñez, co-author of the work and vice-rector for Research at UCAM.
The new research has been published in Nature Aging, and to carry it out, Dr. Izpisua and his collaborators have used this same rejuvenation technology in healthy mice that age naturally (with age). One group of these animals were given regular doses of Yamanaka factors from 15 to 22 months of age (the approximate equivalent in humans from 50 to 70 years); a second group was treated from 12 to 22 months (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 the application of Yamanaka factors over a longer period of time is safe and does not cause tumor formation,” says Pradeep Reddy, co-first author of the new work. The researchers did not observe any negative effects on the health, behavior or body weight of the treated mice compared to those of the control group (untreated, nor were there blood cell alterations, nor neurological changes, nor cancer, in none of the rodents treated.
They did not observe any negative effects on the health, behavior or body weight of the treated mice, nor blood cell alterations, nor neurological changes, nor cancer
Analyzing the signs of aging in the treated mice, the researchers found that they were very similar in many respects to the young animals. For example, the epigenetic patterns of kidney and skin cells from treated animals resembled those of younger animals, and when skin cells from treated animals were injured, their ability to proliferate was greater and they were less likely to form permanent scars than those of untreated animals.
This rejuvenation was seen in mice given Yamanaka factor treatment for seven or 10 months (groups one and two), but not in those treated for only one month (group three). “When the animals were analyzed in the middle of the treatment, the effects were still not so evident. This suggests that the treatment is not just stopping aging, but actively reversing it, although more research is needed to differentiate the two,” says Reddy.
“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,” says Dr. Izpisua Belmonte. “Our results show that, at least in mice, there is a way to achieve this.”
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