Disorders in the functioning of connective tissue underlie the Hutchinson-Gilford Syndrome, or progeria, a rare genetic disease characterized by accelerated aging, according to researchers from Singapore in Developmental Cell.
Hutchinson-Gilford syndrome (progeria – Greek for premature aging) is a very rare genetic disease characterized by premature aging of the body. Progeria is caused by the replacement of just one base – cytosine with thymidine in the LMNA gene encoding lamines A and C, which are structural proteins of the nuclear envelope, resulting in a defective Lamin A, the so-called progerin and the cell nucleus have a disturbed structure. The first symptoms of the disease become visible around 6-12 months of age.
The disease is manifested by significant weight loss and small growth, children gradually lose their hair, eyebrows and eyelashes. Their faces become disproportionately small compared to the rest of the head, with blood vessels clearly visible, the nose acquires the appearance of a bird’s beak, and the eyes bulge out. The skin visibly ages, loses its elasticity, becomes tense, often wrinkled, spots and rashes appear. Children suffer from disorders characteristic of the elderly, such as osteoporosis and cardiovascular disorders. The body age of the patients changes every 8-10 years for each year the patient lives. The average life expectancy of people with progeria is 13-16 years. Children most often die from atherosclerosis of the coronary and cerebral vessels and other diseases typical of old age
The authors of the study, a group of Dr. Colin Stewart from the Institute of Medical Biology in Singapore, decided to investigate how progerin causes progeria and whether similar mechanisms also work during the normal aging process. Scientists had previously bred mice as an animal model of progeria. They have now shown that a mutation in these rodents causes the formation of progerin and that connective tissue cells stop producing intercellular substance after birth of sick mice.
The lack of intercellular substance (matrix) causes cells to stop dividing and die. This only happens in mouse cells after birth, embryonic connective tissue cells function properly – this is an important observation because children with progeria immediately after birth do not have any visible symptoms of the disease.
Scientists have shown that disorders in the connective tissue are related to the action of the so-called Wnt signaling pathway in cells. Now they hope their discovery will help develop new ways to fight the disease.
The authors suggest that the production of abnormal lamine also takes place in the bloodstream during normal aging, which suggests that some mechanisms operating in children with progeria also take place during physiological aging of the body. (PAP)