Impact of Progerin Expression on Adipogenesis in Hutchinson-Gilford Progeria Skin-Derived Precursor Cells.
Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the loss of general subcutaneous fat. To determine whether premature cellular senescence is responsible for the altered adipogenesis in patients with HGPS, we evaluated the differentiation of HGPS skin-derived precursor stem cells (SKPs) into adipocytes. The SKPs were isolated from primary human HGPS and normal fibroblast cultures, with senescence of 5 and 30%. We observed that the presence of high numbers of senescent cells reduced SKPs' adipogenic differentiation potential. Treatment with baricitinib, a JAK-STAT inhibitor, ameliorated the ability of HGPS SKPs to differentiate into adipocytes. Our findings suggest that the development of lipodystrophy in patients with HGPS may be associated with an increased rate of cellular senescence and chronic inflammation.
['Najdi|Farah|F|', 'Krüger|Peter|P|0000-0002-0461-0645', 'Djabali|Karima|K|']
D041721:3T3-L1 Cells D017667:Adipocytes D050156:Adipogenesis D000293:Adolescent D000818:Animals D001384:Azetidines D001896:Boron Compounds D002454:Cell Differentiation D016922:Cellular Senescence D002648:Child D002675:Child, Preschool D019941:Cyclin-Dependent Kinase Inhibitor p16 D050556:Fatty Acid-Binding Proteins D005260:Female D005347:Fibroblasts D006801:Humans D016209:Interleukin-8 D053612:Janus Kinases D034904:Lamin Type A D008297:Male D051379:Mice D047495:PPAR gamma D011371:Progeria D047428:Protein Kinase Inhibitors D011687:Purines D011720:Pyrazoles D012867:Skin D013234:Stem Cells D013449:Sulfonamides
progerin adipogenesis skin-derived precursor cells senescence adipocyte