Spanish study may lead to better therapies for cancer and progeria

Premature aging diseases provide ‘models’ through which many hope to gain insight into the human aging mechanism. They provide an effective model for analyzing the body’s maturation process. The observation in mice of the effects of Prelamin A, the protein that causes progeria, has shed some light in the complex connection taking place between the ageing processes and cancer, since these are closely related. Several years of collaboration between the Institute of Molecular and Oncological Medicine of Asturias (Imoma) and the University of Oviedo has lead to new findings. The spanish scientists discovered that the protein Prelamin A, that speeds up ageing, may slow cancer.

In order to carry out their research, the Spanish scientists have used mosaic mice, genetically modified, to keep 50% of cells with Prelamin A in their tissues during their whole life. The study showed that the Prelamin A causes progeria through cell-extrinsic mechanisms, but also prevents cancer. Suprisingly, these mosaic mice are completely healthy and do not show progeria in spite of having the ageing protein in half of their cells. They live as long as normal mice. This suggests that in order to treat fast ageing it would not only be necessary to fix defects from the affected patient’s cells.

The study made two important discoveries. Firstly that the mosaics are totally healthy, showing none of the alterations that the mice with progeria caused by prelamin A have. Secondly, although the mosaics develop the same number of tumours as normal mice, they have far fewer malignant tumours (those capable of breaking down the barriers that confine them and invading the surrounding tissue).

Carlos López-Otín, one of the researchers, remarked that the achieved results are very encouraging from the scientific point of view, although the development and application of therapies need to be carefully stated. 

José María Pérez Freije, of the University of Oviedo, noted that 'these results invite hope for treating patients with rapid ageing, as they suggest that it is not necessary to correct defects in all cells, but probably only in some of them'. Rubén Cabanillas, of IMOMA said: 'by inducing prelamina A production in cells obtained from human malignant tumours, we observed that their invasive capacity is drastically reduced'.

The finding that the protein that causes fast ageing, Prelamin A, is capable of halting the advancement of malignant tumors, may allow the development and application of new therapies to fight cancer as well as progeria.

new development in research

The group of researchers led by Carlos Lopez Otin at the University of Oviedo, has found that insulin growth factor - or IGF1 - extends life in an animal model of human premature aging. The work was published yesterday.

The treatment developed by these researchers can extend a 25 percent longevity of mice with progeria. According to the authors, this represents an important step toward understanding the mechanisms involved in the development of this disease. In addition, it raises a new therapeutic option for patients affected by syndromes of accelerated aging, those who develop during the first years of life characteristic symptoms of old age: osteoporosis, loss of subcutaneous fat and hair, and cardiovascular failure, among others.The life expectancy of people with the most common form of progeria syndrome, Hutchinson-Gilford-is less than 20 years.

The scientists used genetically modified mice created previously in his laboratory. And they found that levels of a hormone known as insulin-like growth factor or IGF1 were abnormally low in these conditions. They decided to restore hormone levels, and treatment with IGF1 led to a marked improvement in various alterations in these mice, including weight gain, recovery of subcutaneous fat and locomotive ability, reduced hair loss and increased significant life expectancy.

According Otín, this paper raises an option "to improve the clinical situation and extend the life of those suffering from premature aging." In work previously published in Nature and Nature Medicine, the same researchers from the University of Oviedo reported that the accelerated aging was associated with abnormal activation of protective mechanisms against cancer and designed a pharmacological strategy aimed at blocking the accumulation protein responsible for this disease. This work has led to an international clinical trial, currently underway in Marseille, to treat children suffering from this dreadful disease.
spanish source