Scientifics from the University of Oviedo have identified a gene that causes hereditary accelerated aging
May 05, 2011
The study, managed by Carlos López- Otín and in which researchers from IUOPA and IMOMA also take part, has sequenced the genome of a Spanish family in order to indentify the cause of a strange illness for the very first time and it describes a new type of progeria.A study based on the genome's sequence of Spanish patients with accelerated aging has allowed the identification of a new hereditary shape of this disease and discovering the responsible mutant gene of its development. This research, which has been published today in the prestigious American Journal of Human Genetics magazine, is the first of this type carried out in our country and provides new keys about the molecular mechanisms of human aging.
"Aging is a very complex process that affects most of the biological functions of an organism, but whose molecular causes are, in a great level, still unknown", explains the doctor Carlos López- Otín, professor of Biochemistry and Molecular Biology of the University of Oviedo and director of this study. "During the last years, our knowledge about the molecular mechanisms in charge of human aging has increased due to the study of a group of uncommon diseases called progerias, which cause an accelerated aging in patients".
This study has executed by Scientifics from the University of Oviedo, the University Institute of Oncology from the Principality of Asturias and the Medical Institute for Oncology of Asturias, and it reveals a new kind of progeria in two Spanish families. "When they were two years of age, two of the patients started to show evident signs of accelerated aging, especially by showing osseous problems", describes the doctor Rubén Cabanillas, from the Medical Institute for Oncology of Asturias. "The clinical evaluation which was detailed in these patients revealed that both of them had the same pathological alterations, though they didn't correspond with any other illnesses known to date. Furthermore, both had no mutations in the two genes that, until today, had been described as responsible of similar diseases", he points out.
In order to indentify the genetic mutation which was causing this new disease, researchers sequenced the part of genome that codified the proteins of one of the patients as well as his parents' part. "New techniques of sequence allow us to develop this kind of studies, which were unthinkable three years ago", says the doctor Xosé Antón Puente, teacher of the University of Oviedo. This family's sequence genome has permitted to recognize a mutation in a gene called BANF1, which, up to date, hadn't been described as the cause of any sickness.
The molecular study of a patient of the second family allowed Scientifics to confirm the presence of the same mutation in his genome. Additional studies have permitted to prove that this mutation causes a great decrease in the levels of protein that the BANF1 gene codifies, which leads to defects in the nuclear envelope. This structure is the cover that wraps the core of the cell, where the DNA is, so its alteration causes several changes in the body. Finally, the work has also demonstrated that the introduction of a normal gene in the isolated cells of these patients is enough to recover the correct structure of the nuclear envelope.
Previous studies had proved that the mutation of other genes which are involved in the formation of the nuclear envelope, as the ones called LMNA or ZMPSTE24, develops other syndromes of accelerated aging. These works have allowed the University of Oviedo's group to design a treatment against Hutshinson- Gilford progeria which is currently being tested in patients all around the world. For that reason, the doctor López- Otín stresses that: "It is plausible that the discovery of this mutated gene, which is responsible of this new syndrome of accelerated aging, permits the future development of some therapeutic approximation for these patients. In any case, the work that has just been published confirms the great usefulness of sequencing genomes for the study of strange diseases and illustrates the huge potential of this technology to get a deeper knowledge of human biology".
The work of the participating institutions in this project is funded by the Ministry of Science and Innovation, Cajastur Social Work and the FICYT, María Cristina Masaveu Peterson, Medical Centre of Asturias and Marcelino Botín Foundations.