4722 Genetic and Epigenetic Mechanisms of Adipose Tissue Aging

Tuesday, May 10, 2011: 10:16 AM
Ivona Percec, MD/PhD, Plastic Surgery, University of Pennsylvania, Philadelphia, PA
Goals/Purpose:    The molecular mechanisms responsible for human aging have become of critical importance as the world’s population lives longer and older individuals demand a higher quality of life. The pathways resulting in tissue aging, however, have yet to be understood, thereby limiting our insight into the aging pathway and delaying important therapeutic interventions in the prevention and treatment of aging. The goal of this research program is to establish the genetic and epigenetic factors responsible for human aging using a human adipose tissue as a model for investigation.

Methods/Technique: Subcutaneous adipose tissue samples are collected from male and female patients (ages 18-85), who are undergoing aesthetic surgery by plastic surgeons at the University of Pennsylvania. Adipocytes, stromal vascular fraction (SVF) and adipose-derived stem cells (ADSC) are isolated from each specimen and examined in parallel.  RNA and protein expression is examined in a multi-tiered approach that establishes molecular changes associated with aging in a genome-wise and pathway-specific manner.

Results/Complications: We present genome-wide RNA expression differences acquired during the aging process discovered using microarray chip technology in our model of adipose tissue aging of purified populations of adipocytes, SVFs, and ADSCs from human subcutaneous adipose tissues of different ages, clinical aging phenotypes, and anatomical locations. Secondly, we demonstrate that the human Sirtuin histone deacetylation genes (SIRT1-7), which are known to be involved in longevity and adipose metabolism, regulate adipose tissue aging in a differential manner via specific effects on cell type, anatomical region and aging phenotype. Finally, we demonstrate that features originally thought to be specific to brown adipose tissue (BAT) may in fact be responsible for the variance in subcutaneous adipose tissue aging phenotypes. 

Conclusion: We have established that subcutaneous adipose tissue is an excellent model for the investigation of human aging. By examining molecular changes associated with aging in a genome-wise and pathway-specific manner, we are advancing the understanding of how human tissues age.   

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