Kirkland James L, Tchkonia Tamara, Pirtskhalava Tamar, Han Jianrong, Karagiannides Iordanes
Geriatrics Section, Departments of Medicine and Biochemistry, Boston University, 88 East Newton Street, F435, Boston, MA 02118, USA.
Exp Gerontol. 2002 Jun;37(6):757-67. doi: 10.1016/s0531-5565(02)00014-1.
In advanced old age, fat depot size declines while lipid is redistributed to muscle, bone marrow, and other tissues. Decreased fat depot size is related to reduced fat cell size and function and impaired differentiation of preadipocytes into fat cells. Reduced differentiation-dependent gene expression results from decreased abundance of the adipogenic transcription factors, CCAAT/enhancer binding alpha (C/EBPalpha) and peroxisome proliferator activated receptor gamma (PPARgamma). Increased expression of anti-adipogenic C/EBP family members contributes, perhaps due to cellular stress response pathway activation with aging. Hence, dysfunctional adipocyte-like cells appear in adipose tissue that are smaller and less insulin responsive than fully differentiated fat cells. Adipogenesis can be restored by overexpressing adipogenic transcription factors in preadipocytes from old animals. Redistribution of lipid to extra-adipose sites with aging could result from loss of lipid storage capacity in fat depots, altered fatty acid handling resulting in lipid accumulation, dysdifferentiation of mesenchymal precursors, such as muscle satellite cells and osteoblast precursors, into a partial adipocyte phenotype, or a combination of these mechanisms. Thus, accumulation of mesenchymal adipocyte-like default (MAD) cells in fat depots, muscle, bone marrow, and elsewhere is a potentially reversible process that could contribute to maldistribution of fat in old age.
在高龄阶段，脂肪储存库大小减小，而脂质会重新分布到肌肉、骨髓和其他组织中。脂肪储存库大小的减小与脂肪细胞大小和功能的降低以及前脂肪细胞向脂肪细胞分化受损有关。分化依赖性基因表达的降低是由于脂肪生成转录因子CCAAT/增强子结合α（C/EBPα）和过氧化物酶体增殖物激活受体γ（PPARγ）丰度的降低所致。抗脂肪生成C/EBP家族成员表达的增加可能起了作用，这或许是由于衰老激活了细胞应激反应途径。因此，脂肪组织中出现了功能失调的类脂肪细胞，它们比完全分化的脂肪细胞更小，对胰岛素的反应也更弱。通过在老年动物的前脂肪细胞中过表达脂肪生成转录因子，可以恢复脂肪生成。随着衰老，脂质向脂肪外部位的重新分布可能是由于脂肪储存库中脂质储存能力的丧失、脂肪酸处理改变导致脂质积累、间充质前体细胞（如肌肉卫星细胞和成骨细胞前体）向部分脂肪细胞表型的分化异常，或这些机制的组合。因此，间充质类脂肪默认（MAD）细胞在脂肪储存库、肌肉、骨髓和其他部位的积累是一个潜在的可逆过程，可能导致老年时脂肪分布不均。
