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A CABD study sheds light on progeria, a rare disease that accelerates premature aging.

A publication in the 'EMBO Journal' has shown that, in the nematode Caenorhabditis elegans, the introduction of the human mutation in the BAF gene leads to the alteration of gene expression and accelerates aging.

This work by the CABD group highlights the importance of the existence of models for the study of rare diseases such as progeria in the search for possible treatments.


The research group of the Andalusian Center for Developmental Biology (CABD), led by Peter Askjaer, a researcher at this joint center of the Spanish National Research Council (CSIC), the Pablo de Olavide University (UPO) and the Andalusian Regional Government, has shed light on progeria in a recent study published in the 'EMBO Journal'.

Progeria is an extremely rare progressive genetic disorder. It causes accelerated aging in children from the first two years of life. At birth, children with progeria usually appear healthy. It is during the first year that the first symptoms begin to appear, such as slow growth, loss of fatty tissue and hair loss. The final causes of death are heart problems or strokes in most children with progeria. The average life expectancy of a child with progeria is about 15 years. Some people with the disease may die younger and others may live longer, even into their 20s.
Alterations in the structure or components of the nuclear envelope of human cells can give rise to a large set of genetic diseases known as laminopathies that affect various tissues, such as cardiomyopathy, muscular dystrophy, neurological conditions, lipodystrophy and premature aging. These diseases arise from mutations in proteins such as BAF, lamins or emerin, which are crucial for nuclear structure.

In humans, a specific BAF mutation (A12T) causes Nestor-Guillermo progeroid syndrome, which results in premature aging and various health problems. This premature aging disease affects a variety of tissues, causing growth retardation, bone defects and scoliosis. Raquel Romero-Bueno tells us that this study carried out during her doctoral thesis focuses on the BAF protein using the worm Caenorhabditis elegans as a working model, where the Nestor-Guillermo progeroid syndrome mutation has been mimicked. Negative effects on fertility, life expectancy and resistance to environmental stress have been observed. In addition, the mutation accelerates the deterioration of nuclear morphology compared to normal cells. At the molecular level, the interaction of BAF with DNA is also affected.




Doors opened by this study

This research, besides contributing to position Caenorhabditis elegans as a relevant model for the study of diseases in complex organisms, will provide knowledge about how a mutation in an essential protein that is expressed throughout development and in all cells of the organism, triggers the onset of symptoms approximately two years after birth in humans. “Until two years of age patients show no obvious signs of the disease, however, we have seen how the mutation affects even at the cellular level. This suggests that we are talking about a disease that affects development and that there may be a series of signs or manifestations prior to the more obvious signs of the disease that until now have gone unnoticed and that in the future we could use as markers of this or other related diseases,” explains the principal investigator of the CABD study, Peter Askjaer.

Similarly, this work sheds light on progeria as a rare disease, as well as contributing to the study of laminopathies, the group of diseases that have in common the functional alteration of the proteins of the nuclear inner lamina. In addition, as Askjaer points out, “it allows us to study the differences between physiological and pathological aging, allowing us to learn more about the natural process of aging, since there are still many enigmas surrounding it,” the researcher concludes.

Romero-Bueno R, Fragoso-Luna A, Ayuso C, Mellmann N, Kavsek A, Riedel CG, Ward JD, Askjaer P. A human progeria-associated BAF-1 mutation modulates gene expression and accelerates aging in C. elegans. EMBO J. 2024 Oct 4.
DOI: 10.1038/s44318-024-00261-8 . Epub ahead of print. PMID: 39367234.

This press release was written in collaboration with the department of Communication of CSIC Andalucía Extremadura.