Hutchinson-Gilford Progeria as a Window into Human Aging: Genetic, Cellular, and Therapeutic Perspectives
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Abstract
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare and devastating genetic disorder characterized by premature aging. This condition is caused by an autosomal dominant mutation in the LMNA gene, which leads to the production of the defective protein progerin, responsible for cellular changes that induce accelerated aging. The first signs of HGPS usually appear between 6 and 12 months of age, with clinical manifestations such as growth delay, loss of body fat, alopecia, and bone abnormalities. As the disease progresses, severe cardiovascular problems develop, primarily atherosclerosis and fibrosis, leading to death from heart failure or myocardial infarction at an average age of 14.5 years. Diagnosis is confirmed by genetic sequencing for the c.1824C>T mutation in LMNA. Although there is no cure, the farnesylation inhibitor lonafarnib has been shown to improve quality of life and extend survival. The study of HGPS provides a unique window into understanding aging, as it shares molecular mechanisms with natural senescence, such as mitochondrial dysfunction and oxidative stress. Research on HGPS not only deepens our knowledge of this disease but also opens new therapeutic pathways for age-related conditions.
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