They manage to reverse the aging process in mice

As we age, not only does our appearance and health change, but also every cell in the body carries a molecular clock that records the passage of time. Now scientists have managed to reverse the aging process in mice by partially restoring their cells to more youthful states.

Specifically, the team led by Spanish scientist Juan Carlos Izpisúa has shown that it can safely and effectively delay this process in middle-aged and elderly mice. The results are published in the journal Nature Aging.

“In addition to addressing age-related diseases, this approach can provide the biomedical community with a new tool to restore tissue and body health, improving cell function and resilience in different disease situations, such as neurodegenerative diseases”, summarizes the scientist.

Izpisúa is a researcher at the Gene Expression Laboratory of the Salk Institute in La Jolla (California, USA), who has carried out this work in collaboration with Genentech, of the Roche group.

The results that are now known have years of laboratory behind them. Izpisúa and his team discovered in their day that, by altering the dose, frequency and duration of molecules called Yamanaka factors, they could program cells to increase their resilience and functionality “in vitro”.

It is about cellular reprogramming, a process in which, through the activity of four proteins – Yamanaka factors – it is possible to transform any adult cell into an induced pluripotent stem cell, capable of dividing indefinitely and then becoming any type of cell. cell. The discovery of this process by the Japanese Shinya Yamanaka earned him a Nobel Prize.

After the “in vitro” findings, in 2016 the team reported its advances in animals for the first time: then we observed, recalls Izpisúa, that this treatment counteracted the signs of aging and increased life expectancy in mice with a disease of premature aging.

More recently, in 2021, they found that even in young mice, these factors can accelerate muscle regeneration; “Following these observations, scientists have used our methodology to improve the function of other tissues, such as the heart, brain or optic nerve,” he adds.

The study that is now being published had a dual purpose: to check if the beneficial effects previously observed in mice with various diseases also occurred in mice without pathologies and if it happened at different stages of life.

Therefore, a group of mice received regular doses of Yamanaka factors from 15 to 22 months, which is roughly equivalent to 50-70 years in humans.

Another group was treated from 12 to 22 months (35-70 years in humans) and a third for only one month at the age of 25 months (about 80 years in humans).

“We did not observe any negative effects on the health, behavior or body weight of these animals,” Salk’s Pradeep Reddy said in a statement.

Compared with control animals, there were no blood cell abnormalities or neurological changes in those receiving Yamanaka factors; the team found no cancers – an increased risk is associated with aging – in either group.

When the researchers looked at the normal signs of aging, they found that in many ways they resembled younger mice: in kidneys and skin, the epigenetics of the treated animals more closely resembled the epigenetic patterns seen in the younger ones.

Epigenetic markers, influenced by the environment and closely linked to lifestyle, are the chemical marks that control our genetics and change the way genes are expressed.

The scientists also found that, when injured, the skin cells of the treated mice had a greater ability to proliferate and were less prone to permanent scarring – older mice showed less proliferation and more scarring.

This youth was found in animals treated with Yamanaka factors for seven or ten months, but not in those treated for a single month. Furthermore, when treated animals were analyzed midway through the procedure, the effects, while present, were still not as pronounced.

In contrast, when it was done with older animals, one month of treatment was enough to show all the beneficial effects.

This suggests that the treatment is not just stopping aging, but is actively reversing it. However, the authors caution, more research is needed to differentiate the two.

“We want to restore resilience and function to old cells so that they are more resistant to stress, injury and disease. This study shows that at least in mice there is a way to achieve this”, says Reddy.

“The transfer to the clinic could mean a change in current medicine, helping to reverse and prevent some diseases, injuries and dysfunctions that our body accumulates throughout life,” concludes Izpisúa.