Organismal Dynamics

Genetic regulation of ageing in Caenorhabditis elegans

Dr Manuel J. Muñoz

Principal Investigator

Summary 


Aging is a degenerative phenomenon that affects virtually all multicellular organisms, including humans, and represents the main risk factor for most common diseases. The organism that has contributed the most to the biological understanding of this process is undoubtedly the nematode Caenorhabditis elegans. Our group works on the identification and characterization of these types of genes to better understand the regulatory pathways of longevity (DOI: 10.1016/S0047-6374(02)00168-9; DOI: 10.1111/j.1474-9726.2005.00150.x; 10.1111/j.1474-9726.2011.00747.x; 10.1038/s41467-020-20269-y).
In recent years, we have been particularly interested in understanding how the regulation of sulfated steroid hormone levels generates an increase in longevity and improves phenotypes of protein aggregation models (10.1038/s41467-020-20269-y). The increase in these types of hormones can be generated by mutation in the steroid hormone sulfatase or pharmacologically through treatment with specific inhibitors of this enzyme, which produces the same beneficial effect in C. elegans and murine models (10.1038/s41467-020-20269-y). The possibility of using these inhibitors, especially the drug STX64, for the treatment of neurodegenerative diseases has encouraged us to establish the Spin-Off Olavide Neuron STX, which aims to test this compound for the treatment of neurodegenerative diseases in humans (https://onestx.bio/).

Other Projects
The ease with which the nematode C. elegans can undergo genetic modifications and screenings of drugs or natural extracts, together with the fact that approximately 50% of the genes present in OMIM have an ortholog in this organism, allows it to be used simply as a model for both rare and common diseases. In this regard, our group has generated several models of rare diseases, such as galactosemia type III (10.1534/genetics.114.170084; 10.1016/j.biopha.2024.117677) or spinal muscular atrophy (10.1016/j.biopha.2025.118610), proposing possible treatments that have subsequently been validated in mammalian models.

Other activities
Due to this ease in drug screening and the large number of disease models available in this organism, our group offers a service for companies and research groups for drug and extract screenings: https://www.upo.es/upotec/catalogo/salud/unidad-de-ensayos-validacion-actividad-biologica/
The translation of research results into possible applications is essential for the development of society. In our region, despite having numerous research groups working in basic science, there is very little experience in managing research results to generate new products or services. Our research group is promoting teaching activities and meetings with experts with the aim of training people to become promoters and protagonists of research transfer in our environment: https://www.upo.es/formacionpermanente/microcredenciales/introduccion-a-la-gestion-del-conocimiento-en-las-empresas-biomedicas/

Five relevant publications 


 

  • Inhibition of acid sphingomyelinase increases SMN levels and connects sphingolipid metabolism to Spinal Muscular Atrophy. (2025). Brokate-Llanos AM, Beltran M, Garzón A, Garcera A, Miralles MP, Celma-Nos F, Campoy-López A, Soler RM, Muñoz MJ, Pérez-Pulido AJ.  Biomedicine & Pharmacotherapy. 192, November, 118610. doi: 10.1016/j.biopha.2025.118610.
  • Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway. (2024).  Lucas-Rodríguez P, Brokate-Llanos AM, Hernandez-Curiel JM, Murdoch PDS, Garzón A, Carrión A, Muñoz MJ. Biomedicine and Pharmacotherapy  181, December, 117677. doi: 10.1016/j.biopha.2024.117677.
  • Nematode biomass production from sewage sludge as a novel method for circular economy. (2022). López-Viso C., Hodaifa G., Muñoz M. J. Journal of Cleaner Production 330. DOI: 10.1016/j.jclepro.2021.129706
  • Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases. (2021). Pérez-Jiménez MM, Monje-Moreno JM, Brokate-Llanos AM, Venegas-Calerón M, Sánchez-García A, Sansigre P, Valladares A, Esteban-García S, Suárez-Pereira I, Vitorica J, Ríos JJ, Artal-Sanz M, Carrión ÁM, Muñoz MJ.  Nature communication; 12-49. doi: 10.1038/s41467-020-20269-y.
  • Positive selection of Caenorhabditis elegans mutants with increased stress resistance and longevity. (2003). Muñoz, M.J., Riddle, D.L. Genetics, 163(1), pp. 171–180. DOI: 10.1093/genetics/163.1.171

Lab members & Collaborators


 

Lab members

Group leader

Manuel J. Muñoz, +34 954349387

Senior Researchers

Mercedes Pérez Jiménez
Ana María Brokate Llanos

PhD students

Cristina García Gutiérrez
Javier Valle Galisteo

Lab Manager

Laura Garzón Alvarez

Former students

José Manuel Monje Moreno (PhD)
David Guerrero Gómez
Alejandra Cano Ruiz (Technical specialist)

Collaborators

Dr. Angel Carrión (Universidad Pablo de Olavide, ESPAÑA)
Dr. Rosa M. Soler (Universitat de Lleida, ESPAÑA)
Dr. Rafael Guillén-Bejarano (Instituto del Grasa, CSIC, ESPAÑA)
Dr. José Manuel Monje Moreno (Universidad Pablo de Olavide, ESPAÑA)
Dr. Sandra Barral (University of Columbia, NY, EEUU)