Abstract
BackgroundChronic 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.ResultsGene 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.ConclusionOur 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.
Highlights
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
The protocol to prepare cells for microarray gene expression analysis was as follows: (Day 1) Cells were plated at 9000–12000 cells per cm2 in regular growth medium; (Day 2) Cell culture medium was changed to growth-factor-free medium (EMEM with 0.2% BSA and 1% Lglutamine); (Day 3) Cells were washed with ice cold phosphate-buffered saline (PBS)
We focus on differences in quiescent fibroblasts derived from donors of different biological ages
Summary
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. Immunity & Ageing 2008, 5:5 http://www.immunityageing.com/content/5/1/5 autoimmune processes caused by deregulation of the immune system [4,5] These states may arise as a consequence of an increased cell stress response in old cells triggered by molecular damage incurred over a lifetime. Molecular events observed during replicative senescence in vitro do not necessarily mirror events that occur in human aging, which is of a dramatically different time frame. This consideration motivated the present investigation of age-associated changes in proliferating fibroblasts derived from donors at different biological ages. Few reports using fibroblasts aged in vivo have been published and these reports largely focused on age-associated changes in cell cycle progression of dividing cells [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
