Aging Cell: Rejuvenating mouse organs through cellular reprogramming

Many diseases, including cancer, are associated with aging and are becoming more common as life expectancy increases
.
Therefore, it is critical to study and understand these processes if we are to address them and also promote healthier ageing
.

One area of ​​aging research involves rejuvenation, the restoration of the properties of young cells in aged cells or tissues
.

Led by ICREA researcher Dr.
Manuel Serrano, scientists from the IRB Cell Plasticity and Disease Laboratory in Barcelona have successfully reprogrammed a number of mouse organs and tissues to rejuvenate
.
Specifically, scientists have observed significant changes in the animals' pancreas, liver, spleen and blood
.

"This work aims to identify the initial processes of reprogramming and cell regeneration in vivo, and to identify those processes that can be modified by drug or nutritional levels in future studies," explained Dr.
Serrano
.

Yamanaka factors and cellular reprogramming

All tissues in our body have highly specialized cells such as neurons or muscle cells
.
The properties of these cells were thought to be fixed until Japanese researcher Shinya Yamanaka found a way to alter their properties (that is, "reprogram" them) by introducing high levels of of four proteins, namely "Yamaka factors" (OCT4, SOX2, KLF4 and MYC)
.
While these proteins can be found in some of our cells, it is the presence of high levels of all four proteins that alter cellular properties
.

This regenerative technology can do what was previously unimaginable by taking easily accessible cells from a patient, such as skin cells, and converting them into other cells that are difficult or impossible to harvest, such as heart cells or neurons, and then using for cell therapy applications
.

For these advances, Yamanaka won the Nobel Prize in Medicine in 2012, just six years after his discovery
.

In 2013, a study led by Dr.
María Abad and Dr.
Serrano reported successful cellular reorganization in laboratory animals, that is, without the need to extract naive cells, reconstitute them in vitro, and then implant them
.
It is important to note, however, that altering the properties of cells in living tissue can lead to considerable imbalances in the tissue, losing their function and eventually leading to a type of tumor called a teratoma, which is typical of the embryonic state
.
Nonetheless, these findings pave the way for studying reprogramming directly in animals
.

milestones in organ regeneration

Three years later, Juan Carlos Dr.
Izpisúa-Belmonte's lab in La Jolla, Calif.
, observed that when reprogramming begins in animals and is interrupted halfway through, cells return to their original state, preventing cell imbalance and Teratoma
.

To their surprise, Dr.
Izpisúa-Belmonte's team observed that when this partial and reversible reprogramming process is repeated over multiple cycles, it leads to cellular regeneration throughout the organism, making mice healthier and less susceptible to each other.
better protection against diseases
.

Therefore, in 2016, this method of cell regeneration has attracted great interest, although this method is not fully understood at present and is the focus of research in numerous laboratories
.

This is another step in understanding aging

In this latest study, published in the journal Aging Cell, the researchers examined the effects of a single cycle of Yamanaka factor stimulation in order to better define the mechanisms involved
.
To this end, they explored changes in metabolism, gene expression, and cellular DNA state during aging, and how these changes are partially reversed by reprogramming
.

"We wanted to study the initial effects of the regeneration process and it was a surprise to see such a dramatic improvement at the molecular level, especially in the pancreas," said Dr.
Daphne Chondronasiou, first author of the article
.

Original search:

Dafni Chondronasiou, Diljeet Gill, Lluc Mosteiro, Rocio G.
Urdinguio, Antonio Berenguer‐Llergo, Mònica Aguilera, Sylvere Durand, Fanny Aprahamian, Nitharsshini Nirmalathasan, Maria Abad, Daniel E.
Martin‐Herranz, Camille Stephan‐Otto Attolini, Neus Prats, Guido Kroemer, Mario F.
Fraga, Wolf Reik & Manuel Serrano
Aging Cell  (2022) DOI:  10.