Researchers find ways to neutralize them and improve tissue regeneration – ScienceDaily

Researchers at the Universitat Pompeu Fabra (UPF), ICREA, CIBERNED, CNIC and Altos Laboratories and other national and international collaborators have described how damaged cells (senescent cells) that inevitably occur after injury negatively affect tissue regeneration and how this mechanism works. actively in old age, but surprisingly also at a young age. This negative effect can be overcome genetically and pharmacologically, so stem cell regenerative functions can be restored.

Tissue regeneration is dependent on the stem cell population and neighboring cells, a process whose effectiveness declines with aging. The reasons for this decline are largely unknown.

Dr. Pura Muñoz-Cánoves is a professor of ICREA in the Department of Medicine and Life Sciences (MELIS) ​​at UPF in Barcelona, ​​CNIC in Madrid and CIBERNED, and now at Altos Labs San Diego Institute of Science and Dr. Eusebio Perdiguero (also from MELIS and now at Altos Laboratories) has found in experiments with mice that senescent cells are novel regulatory components of the muscle-regenerating niche that blunt muscle regeneration at all stages of life.

Cellular senescence is an irreversible cell cycle arrest that usually occurs after tissue damage and in age-related diseases. Cells do not die, they remain in hibernation. Aging, along with apoptosis (a form of programmed cell death), is one of the mechanisms the body uses to control the unwanted proliferation of tumors. Therefore, the study of these cells is of great biomedical importance. In addition, senescent cells affect tissue repair processes and beneficial effects as tumor suppressors have been documented during embryo development and during liver and skin repair or reprogramming.

Despite these reasons, few studies have attempted to profile and characterize them in vivo. This is largely attributed to the rarity and rarity of these cells, even in aged tissues.

In a study published today Nature, the research team created the first transcriptomic atlas of aged cells of damaged skeletal muscles of mice of different ages (transcriptomics refers to structures that replicate anything related to RNA or information originally encoded within a nucleus cell). The researchers found that senescent cells are largely heterogeneous, but exhibit common characteristics, including the secretion of proinflammatory and profibrotic (promoting an excess of fibrous connective tissue) factors. This secretion affects nearby stem cells and inhibits their regenerative capacity, thereby impairing muscle regeneration. So, it seems that what was once a good protection tool is now turning into a bad protection tool.

The results showed that reducing the burden of senescent cells (through genetic or pharmacological treatments that cause the death of these cells) improved the regeneration of aged muscles and unexpectedly younger muscles. These benefits in young tissue are due to reduced inflammation in the surrounding stem cell, which nourishes stem cell functions.

“This is consistent with the idea that senescent cells, even in young tissues, create a hyper-inflammatory microenvironment that reflects age-related inflammation (inflammation),” says Pura Muñoz-Cánoves. Thus senescent cells cause the expected senescence of the stem cell niche, even in young mice; Therefore, reducing the aging burden alleviates inflammation of the stem cell niche and improves muscle repair.

“In addition to the biomedical benefits of targeting senescent cells, the new molecular information provided by the muscle senescent cell atlas could possibly be transferred to understand senescence function in other tissues whose senescent cells have not been profiled or have not sufficiently senescent cell numbers,” says Dr. Eusebio Perdiguero.

Increasing work from many groups shows that the effects of senescent cells are diverse (beneficial or harmful) and depend on the tissue environment and type, the duration of injury, the degree of persistence of senescent cells, and the age of the organism. Therefore, Dr. “The roles of senescent cells must be studied in different contexts in normal, aged, and disease states,” says Muñoz-Cánoves. In this line, he adds, “in total, the information shown in this article will be instrumental in advancing our knowledge of senescent cells and finding new treatments to target them in the context of regenerative medicine and aging.”

This scientific work also includes the collaboration of researchers from Kyushu University (Fukuoka, Japan), Altos Labs San Diego Institute (San Diego, USA), University of Tokyo (Tokyo, Japan), Guangzhou Institutes of Biomedical and Health, China. Academy of Sciences (Guangzhou, China), CIC bioGUNE (Derio, Spain), Biomedical Research Institute (IRB Barcelona), Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg (Luxembourg). The work was funded in part by grants from the European Research Council (ERC), the Spanish Ministry of Science and Innovation, the La Caixa Foundation, AFM, MDA, MWRF and DPP-Spain.

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