Cell autonomous expression of inflammatory genes in biologically aged fibroblasts associated with elevated NF-kappaB activity
1 School of Biomedical Engineering, Science and Health Systems, Drexel University, Bossone Research Center, 3141 Chestnut Street, Philadelphia, PA 19104, USA
2 Coriell Institute for Medical Research, 403 Haddon Avenue, Camden, NJ 08103, USA
3 Dept. of Dermatology and Cutaneous Biology, Thomas Jefferson University, 233 South 10th Street, Suite 326 BLSB, Philadelphia, PA 19107, USA
Immunity & Ageing 2008, 5:5 doi:10.1186/1742-4933-5-5Published: 16 July 2008
Chronic inflammation is a well-known corollary of the aging process and is believed to significantly contribute to morbidity and mortality of many age-associated chronic diseases. However, the mechanisms that cause age-associated inflammatory changes are not well understood. Particularly, the contribution of cell stress responses to age-associated inflammation in 'non-inflammatory' cells remains poorly defined. The present cross-sectional study focused on differences in molecular signatures indicative of inflammatory states associated with biological aging of human fibroblasts from donors aged 22 to 92 years.
Gene expression profiling revealed elevated steady-state transcript levels consistent with a chronic inflammatory state in fibroblast cell-strains obtained from older donors. We also observed enhanced NF-κB DNA binding activity in a subset of strains, and the NF-κB profile correlated with mRNA expression levels characteristic of inflammatory processes, which include transcripts coding for cytokines, chemokines, components of the complement cascade and MHC molecules. This intrinsic low-grade inflammatory state, as it relates to aging, occurs in cultured cells irrespective of the presence of other cell types or the in vivo context.
Our results are consistent with the view that constitutive activation of inflammatory pathways is a phenomenon prevalent in aged fibroblasts. It is possibly part of a cellular survival process in response to compromised mitochondrial function. Importantly, the inflammatory gene expression signature described here is cell autonomous, i.e. occurs in the absence of prototypical immune or pro-inflammatory cells, growth factors, or other inflammatory mediators.