Lamin A/C deficiency is associated with fat infiltration of muscle and bone

作者：Tong Jessica; Li Wei; Vidal Christopher; Yeo Li Sze; Fatkin Diane; Duque Gustavo^*

来源：Mechanisms of Ageing and Development, 2011, 132(11-12): 552-559.

DOI：10.1016/j.mad.2011.09.004

• Osteopenia
• Sarcopenia
• Ageing
• Frailty
• Lamin A/C
• Adipocytes

Sarcopenia and osteopenia are two common components of the frailty syndrome that may share a common underlying mechanism. Since frailty has been associated with increased fat infiltration in muscle and bone, we hypothesized that lamin A/C, a protein of the nuclear envelope that regulates adipose differentiation, could be associated with the pathophysiology of both osteo and sarcopenia in the frailty syndrome. Four-week-old lamin A/C null (Lmna(-/-)), heterozygous (Lmna(+/-)) and wild type (WT) mice were sacrificed and their mid-thigh analyzed for fat infiltration using invasive (histology) and non-invasive (mu CT) methods. Lmna(-/-) mice showed a significant increase in inter- (similar to 4-fold) and intra-myofiber (similar to 2.5-fold) fat and marrow fat infiltration (similar to 40-fold), with a significant decrease in muscle volume (-42.8%) and bone volume (-21.8%), as compared with WT controls. Furthermore, fat infiltration happened concomitantly with a significant decline in muscle and bone strength in Lmna(-/-) - mice. From a mechanistic approach, high levels of pro-adipogenic factors PPAR-gamma and C/EBP alpha were associated with a reduction in myogenic and osteogenic factors from the Wnt-10b/beta-catenin signalling pathway in Lmna(-/-) mice. In conclusion, lamin A/C could constitute the determinant factor in the pathogenesis and potential treatment of both sarcopenia and osteopenia, which are commonly observed in the frailty syndrome.

• 出版日期2011-12