Taiwanese team finds possible cause of premature aging illness
Taipei, Oct. 12 (CNA) Taiwanese researchers have found that a deficiency in the primary cilium on cells could be the key to understanding progeria, a rare progressive genetic disorder that causes children to age rapidly and subsequently die young.
The research results were published as the featured study in a recent edition of EMBO Reports, a peer-reviewed scientific journal covering research related to biology at a molecular level.
Patients with progeria, also known as Hutchinson-Gilford progeria syndrome, develop symptoms in infancy and have an average life expectancy of 13 years. The clinically observable traits include severe growth retardation, loss of subcutaneous fat, wrinkled skin, hair loss, osteoporosis, joint stiffness, and cardiovascular diseases.
Despite being first described in 1886, progeria was not attributed to mutations in the LMNA gene until 2003. This is the gene that provides instructions to make several slightly different proteins called lamins. The two major proteins produced from this gene, lamin A and lamin C, are made in most cells.
When the LMNA gene mutates, there are abnormal wrinkles on the nucleus, which can even deform and hollow out, said Chen Hong-chen (陳鴻震), the professor in molecular biology at National Yang-Ming University who led the research team, at a press conference held by the Ministry of Science and Technology (MOST) in Taipei Monday.
For the first time the team found a link between the abnormality of the nucleus and the primary cilium on the surface of the cell, after observing that the skin fibroblasts -- the principal active cell of connective tissue -- had fewer and shorter primary cilia in progeria patients.
Since the primary cilium functions like a cellular antenna that detects changes in the extracellular environments and transduces signals to the cell interior to respond to those changes, it is possible that the malfunction of primary cilia could cause progeria, he said.
The team further examined LMNA null mice (mice that have a gene knocked-out by the targeted integration of a defective gene), and proved that primary cilia were defective in many organs of prematurely aged, lamin A-deficient mice, Chen said.
The research team found that mice with an LMNA deficiency had a lifespan of 4-5 months, much shorter than normal mice. With genetic engineering, it was also possible to fix that deficiency, according to Chen.
"This discovery not only provides new insights for the pathogenesis of progeria syndrome, but also sheds light on new therapeutic strategies for related diseases," the science ministry said in a statement released Monday.
The research featured in the Oct. 5 issue of EMBO Reports, published by the European Molecular Biology Organization, under the title "Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis."
The study led by Chen's team was sponsored by the MOST and conducted mainly by postdoctoral fellow Fan Jia-rong (范嘉榕) (first author of the paper), associated researcher Chi Ya-hui (紀雅惠) of the National Health Research Institutes, and Professor You Li-ru (游麗如) and Associate Professor Wang Won-jing (王琬菁) of the Institute of Biochemistry and Molecular Biology under National Yang-Ming University.
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