Anti-oxidant sensitivity of donor age-related gene expression in cultured fibroblasts.
Cultured human fibroblasts display age-dependent transcriptomic differences. We hypothesized that aging-associated oxidative stress affects gene expression, and monitored the transcriptome in confluent fibroblasts from young and old individuals cultured without and with a lipophilic and hydrophilic anti-oxidant mixture (vitamin E, quercetin, hydroxytyrosol and kaempferol). In cells derived from old subjects genes with lower expression were related to oxidative stress, growth and differentiation, cell cycle or metabolic enzymes and with higher expression to protein processing and docking, extracellular matrix, immune response, EGF-signalling and transcription. Anti-oxidant treatment modulated a similar number of genes in all donors and induced cell cycle regulatory genes. A subset of genes, modulated by age and inversely modulated by anti-oxidants, included glutaminase. Despite increased glutaminase expression, donor age-dependent decline in glutathione content and resistance to glutathione-depletion was observed. Summarizing, gene expression of fibroblasts is affected by donor age and a subset was corrected by anti-oxidants. Thus, in cultured fibroblasts from aged donors, gene expression is partly driven by oxidative stress.
Braam
Branko
B
University Medical Center Utrecht, Dept. of Nephrology and Hypertension F03.223, Utrecht, The Netherlands. bbraam@gmail.com
Langelaar-Makkinje
Miriam
M
Verkleij
Arie
A
Bluyssen
Hans
H
Verrips
Theo
T
Koomans
Hein A
HA
Joles
Jaap A
JA
Post
Jan Andries
JA
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000369:Aged, 80 and over; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D005978:Glutathione