Beyond fat grafting: what adipose tissue can teach us about the molecular mechanisms of human aging.

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.