Experiment with promising results: temporarily converting adult cells into stem cells

A team of researchers at the Salk Institute, led by Spaniard Juan Carlos Izpisúa Belmonte, has managed to safely and effectively reverse the cellular aging process in a group of mice and return, albeit partially, the cells of these animals to their youthful state. This technical achievement represents a step forward in understanding how to slow down (and reverse) the effects of the passage of time in animals.

Aging is one of the most important challenges facing the world today and is a major risk factor for many of today's unsolved diseases, and Dr. Izpisúa's work could lead to new therapies for age-related diseases, thus promoting healthy aging.

For nearly 30 years, Izpisúa Belmonte has been a member of the Salk Institute for Biological Studies, attaining the rank of professor in the Gene Expression Laboratory and holding the Roger Guillemin Chair.

Cellular reprogramming

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

This is cell reprogramming, a process in which the activity of four proteins - Yamanaka factors - can transform any adult cell into an induced pluripotent stem cell.

To understand the success of this study, it is worth taking a step back and looking at what happens as we age. Every cell in our body has a built-in 'molecular clock' that keeps track of the passage of time. These 'gears' secrete different patterns of chemicals (also called epigenetic marks) depending on how old we are.

But, what if the “regulating mechanism” of these clocks was to be changed? According to the new study, adding a mixture of four reprogramming molecules ('Yamanaka factors) to cells can restore these epigenetic marks to their original patterns and thus 'restore' some of the original rhythms of these mechanisms.

This technique has been tested in a group of mice aged 15 to 25 months, the equivalent of 50 to 80 years in humans. According to the study, the animals that underwent the treatment showed similar characteristics to the young of their species.

In both the kidneys and skin, the epigenetics of the treated rodents more closely resembled the epigenetic patterns seen in more juvenile animals. When injured, skin cells in the treated animals had a greater ability to proliferate and were less likely to form permanent scars. In addition, metabolic molecules in the blood of these animals showed no normal age-related changes.