Young old mice
An animal model of the rarest genetic disease is presentedDmitry Safin, Compulenta
Biologists from the United States and Singapore have modeled progeria on mice, a disease whose symptoms resemble signs of aging that appear much earlier than usual.
The first case of progeria (Getchinson-Guilford syndrome) was described in 1886. Sick children at birth are no different from the rest, but soon the growth of the child slows down sharply, and the signs of premature aging become more and more noticeable. Each year of a patient's life roughly corresponds to one decade in a healthy person. The average age of children with progeria at the time of death, the cause of which is most often progressive atherosclerosis, is 13 years.
A patient with progeria at the age of three (photo by Jasmine Goldband).
Progeria develops as a result of a mutation in the LMNA gene, which encodes the lamin A protein involved in the formation of nuclear lamina.
(Nuclear lamina is a rigid fibrous structure underlying the membrane of the cell nucleus. In vertebrates, it consists mainly of lamins A, B and C – VM.)
The "truncated" version of lamin A, the so-called progerin, cannot adequately perform its functions, as a result of which the cell nuclei are deformed.
The authors studied a mutation in LMNA that causes muscular dystrophy and cardiomyopathy in humans. As it turned out, in mice, the same mutation corresponds to a condition very similar to progeria. Animals receive "truncated" lamin A, as a result of which connective tissue cells cease to secrete extracellular matrix substances and divide, and then die. However, in the study of embryonic cells, it was not possible to detect such changes. In this, the authors see another similarity with progeria, which does not manifest itself immediately. The mice also had abnormalities in the development of the skull characteristic of progeria, scleroderma, baldness and loss of subcutaneous fat.
Biologists have also shown that changes in the expression level of genes encoding extracellular matrix proteins are associated with defects in the known Wnt signaling pathway. "Our results suggest that progeria is a "disease" of the extracellular matrix of connective tissue, which leads to abnormalities in the development of the skeleton, teeth, skin and vascular network," concludes the head of the research team Colin Stewart, representing the Singapore Institute of Medical Biology. "If the cause here is indeed defects in the Wnt signaling pathway, we will probably be able to find ways to combat progeria."
Full version of the report (Functional coupling between the extracellular matrix and nuclear lamina by Wnt signaling in progeria) published in the journal Developmental Cell.
Prepared based on the materials of Cell Press: New insight into 'accelerated aging' diseasePortal "Eternal youth" http://vechnayamolodost.ru