A research team led by the Spaniard Juan Carlos Izpisúa Belmonte has published a paper in the journal Nature Aging in which they claim to have achieved cell and tissue rejuvenation in mice, using the technique already described by Shinya Yamanaka more than 10 years ago and for which he was awarded the Nobel Prize.
Similarly, the epigenetic information of cells from mice with premature aging has been partially reprogrammed through the expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc). As a consequence, the cells partially recover the genetic state they possessed in juvenile stages, which seems to translate into a regression of the natural aging process, prolonging their useful life.
It has not been shown that this effect can also occur in mice in which premature aging has not been induced.
The authors state that long-term partial epigenetic reprogramming leads to rejuvenating effects in different tissues, such as the kidney, skin, and other tissues.
The rejuvenating effects were associated with epigenetic clock reversal and metabolic and transcriptomic changes, including reduced expression of genes involved in inflammation, senescence, and stress response pathways.
Overall, the researchers state that their observations indicate that partial reprogramming protocols can be designed to be safe and effective in preventing age-related physiological changes. Furthermore, we conclude that long-term partial reprogramming regimens are more effective in delaying aging phenotypes than short-term reprogramming.
In an interview with Diario Médico, Izpisúa stated that his team discovered a few years ago that by altering the dose, frequency and duration of molecules called Yamanaka factors [after the aforementioned Japanese Nobel Prize winner Shinya Yamanaka] they could program cells to increase their resilience and in vitro functionality.
Later, in 2016, they also achieved this with animals in in vivo studies, observing that it could counteract the signs of aging and increased life expectancy in mice with a disease of premature aging. Izpisúa states that “this year our team has discovered that, even in young mice, these factors can accelerate muscle regeneration. Following these initial observations, other scientists have used our methodology to improve the function of other tissues such as the heart, brain or optic nerve.”
The current study aimed, on the one hand, to test whether the beneficial effects previously observed in mice with various diseases also occurred in mice without any pathology, and, on the other hand, whether this phenomenon occurred at different stages of their lives.
The mice were exposed for several months to the rejuvenation molecules at a stage of their lives equivalent to middle and old age in humans.
A reversal of the molecular imprints of aging was observed both in mice treated for a few days in the final stages of their lives and in those exposed to rejuvenation molecules for several months in their youth.
Another novelty of this study is that progress has been made in controlling the level of expression of the Yamanaka factors by treating the mice only two days a week. These two aspects are critical to prevent negative consequences, such as the appearance of tumors, one of the most serious complications of using cell reprogramming techniques. The Yamanaka factors were expressed during a prolonged stage of their lives, and no teratomas were detected during these treatment periods.
Possible future applications in the improvement of degenerative processes associated with aging, in addition to the other therapeutic possibilities already mentioned, give this finding great relevance, pending future trials with human tissues.