Stransky Carrie A, Hsu Vivian M, Dierov Raia, Hoover William J, Donahue Greg, Bucky Louis P, Percec Ivona
Department of Plastic Surgery, Hospital of the University of Pennsylvania,; and Epigenetics Program and the Department of Cell and Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Ann Plast Surg. 2012 Oct;69(4):489-92. doi: 10.1097/SAP.0b013e31824c0e43.
The concept of aging and the mechanisms responsible for soft tissue aging have become progressively more important as the world's population ages and demands a higher quality of life. Although molecular mechanisms of aging have been evaluated in model organisms, specific genomic, genetic, and epigenetic modifications that can be translated to normal human tissue aging have yet to be identified. We propose that adipose tissue is an excellent model with which to investigate molecular aging pathways. The goal of this study is to demonstrate that primary human adipose tissue can serve as a model of human aging, and further, can be used to detect differences in genomic transcriptional profiling between cell types in adipose tissue as well as between youthful and older age groups.
Subcutaneous adipose tissue was excised during cosmetic procedures from healthy patients. Adipocytes and stromal vascular fractions from the anterior abdomen were isolated from 3 young (26-39 years) and 3 old (52-64 years) patients and analyzed for genome-wide transcriptional differences between varying ages and cell types using the Affymetrix GeneChip Human Gene Chip 1.0ST.
Genes specific to adipocytes were more highly expressed in adipocytes than in stromal vascular fractions, validating that adipose tissue should be examined in a cell-specific manner. An increase in overall gene expression was observed among patients in the older age group, consistent with senescence-related chromatin dysregulation. Principal components analysis revealed no clear delineation between age groups and a clear separation by cell type. Analysis of variance revealed cell type as the most significant variable in transcriptional differences, whereas age-related differences were a distant second. Gene Ontology categories of the most significantly modified genes included RNA splicing and mRNA metabolism, plasma membrane, and mitochondrial metabolism.
Primary adipose tissue is an effective model for the study of the molecular mechanisms of human aging. Our findings are consistent with the hypothesis that epigenetic modifications play a more important role than transcriptional modifications in early human adipose tissue aging. Our future studies will examine the contribution of specific epigenetic markers to human adipose tissue aging and promise to advance approaches in regenerative medicine, and the prevention and treatment of aging.
随着全球人口老龄化以及对生活质量要求的提高，衰老概念和导致软组织衰老的机制变得越来越重要。尽管在模式生物中已经对衰老的分子机制进行了评估，但尚未确定可转化为正常人类组织衰老的特定基因组、遗传和表观遗传修饰。我们认为脂肪组织是研究分子衰老途径的理想模型。本研究的目的是证明原代人脂肪组织可作为人类衰老的模型，并且进一步可用于检测脂肪组织中不同细胞类型之间以及年轻和老年组之间基因组转录谱的差异。
在美容手术过程中从健康患者身上切除皮下脂肪组织。从3名年轻（26 - 39岁）和3名老年（52 - 64岁）患者的前腹部分离脂肪细胞和基质血管成分，并使用Affymetrix GeneChip Human Gene Chip 1.0ST分析不同年龄和细胞类型之间的全基因组转录差异。
脂肪细胞特异性基因在脂肪细胞中的表达高于基质血管成分，证实应以细胞特异性方式检查脂肪组织。老年组患者中观察到整体基因表达增加，这与衰老相关的染色质失调一致。主成分分析显示年龄组之间没有明显划分，但细胞类型之间有明显分离。方差分析显示细胞类型是转录差异中最显著的变量，而与年龄相关的差异则远居其次。最显著修饰基因的基因本体类别包括RNA剪接和mRNA代谢、质膜以及线粒体代谢。
原代脂肪组织是研究人类衰老分子机制的有效模型。我们的研究结果与以下假设一致，即表观遗传修饰在早期人类脂肪组织衰老中比转录修饰发挥更重要的作用。我们未来的研究将研究特定表观遗传标记对人类脂肪组织衰老的贡献，并有望推进再生医学以及衰老预防和治疗方面的方法。
