Progeria: a human-disease model of accelerated aging.
Progeria is a rare genetic disease with striking features that resemble accelerated aging. The inheritance pattern, paternal age effect, and lack of consanguinity argue that it is due to a sporadic dominant mutation. We have observed elevated levels of hyaluronic acid (HA) excretion in progeria patients. In several progeria patients we observed normal levels of growth hormone (GH) but very low levels of insulin-like growth factor I along with very high basal metabolic rates (BMRs). A trial of GH treatment was begun, which resulted in a marked increase in linear growth and a paradoxical drop in BMRs in these two patients. We hypothesize that the failure of patients with progeria to thrive may be due to a bioinactive form of GH and a lack of vasculogenesis caused by excess HA. An understanding of the progeria genetic mutation may define a key gene with a major effect on normal aging.
Brown
W T
WT
Department of Human Genetics, New York State Institute for Basic Research, Staten Island 10314.
D001481:Basal Metabolism; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000652:urine*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D009154:Mutation; D011371:Progeria / Q000235:genetics / Q000378:metabolism*; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D006820:Hyaluronic Acid