Cellular senescence is characterized by a cell cycle arrest and active secretory metabolism, termed senescence-associated secretory phenotype (SASP). Senescent cells participate in numerous biological, physiological, and pathological processes, including embryonic development, cancer, and aging-related diseases.

Despite the important advances in recent years, there are multiple open questions about the functionality, physiological relevance of the senescence program and its role in the pathogenesis of different diseases, as well as its possible manipulation for therapeutic purposes.

Using a multidisciplinary approach and cutting-edge technologies at SenesceX we propose:

1. Determine how dysfunctional senescence contributes to developmental defects in
   human BranchioOtoRenal (BOR) and CHARGE syndromes, using mouse models.
2. Characterize the dual role of senescence in tumor initiation and progression, its connection with stem phenotypes and the therapeutic potential of senogenic and senolytic in breast cancer models.
3. Investigate the connection between senescence and latent tumor cell (dormancy) by generating a mouse model, for the identification and monitoring of non-existent cells.
   proliferating (dormant or dormant).
4. Analyze cellular communication in senescence during aging and processes
   neurodegenerative as well as their manipulation for rejuvenation.
5. Identify new vulnerabilities of senescent cells in the pathologies described by genetic and  harmacological screening.

Research into cellular senescence is one of the most dynamic areas of research. basic and translational biomedicine for its broad impact on multiple diseases and its novel approaches. In this proposal, different experimental approaches will be used, from molecular and cellular analyses, massive analyzes (scRNAseq, ATACseq, proteomics, metabolomics), studies in animal models and genetic and pharmacological screenings.

The multidisciplinary and complementary approaches, together with the track record and experience of the partners involved, guarantee the success of the objectives set. This proposal will clarify the role of senescence in processes as disparate as embryonic development, aging and cancer and aims to provide new therapeutic strategies to combat diseases derived from inefficient senescence.