Accelerated Aging: Human Progeroid Syndromes

In contrast to Werner syndrome, the symptoms of Hutchinson-Gilford syndrome (progeria) appear in infancy. Premature aging characteristics associated with progeria are loss of hair, reduction in subcutaneous fat, wrinkling of the skin, skeletal abnormalities (including osteoporosis), and severe atherosclerosis. Growth retardation and other features not associated with aging are also observed, but mental development appears normal. Progeria patients usually succumb by their early teens due to complications from atherosclerosis.

Progeria is extremely rare, striking about one in ten million individuals. The lack of an inheritance pattern implicates sporadic dominant mutations as the underlying cause. The most prevalent physiological abnormality associated with progeria is elevated hyaluronic acid in the urine. Notably, hyaluronic acid levels in the urine normally increase with age, although not approaching the levels observed in progeria. Hyaluronic acid is involved in maintenance of the skeletal, muscular, cutaneous, and vascular systems of the body, and is thought to block angiogenesis (vascularization). A potential defect in hyaluronic acid metabolism may thus disrupt many developmental pathways. Cells from Hutchinson-Gilford patients appear to have diminished replicative capacity, but not nearly as short a life span as cells from Werner patients. Nevertheless, the genetic and biochemical causes of progeria remain unknown.