کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8264253 | 1534885 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inadequate mito-biogenesis in primary dermal fibroblasts from old humans is associated with impairment of PGC1A-independent stimulation
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کلمات کلیدی
TFAMmitochondrial DNA polymerase gammaΔΦPGC1aMitochondrial rRNA12SPOLGWntNRF1AMPKGSEACCCPmTORSirt1FDRAICARqPCRpAMPK - LLLNAD+ - NAD +PCA - PCAROS - ROSMitochondrial gene expression - بیان ژن میتوکندریزیGene Set Enrichment Analysis - تجزیه و تحلیل غنی سازی مجموعه ژنیPrincipal component analysis - تحلیل مولفههای اصلی یا PCAAgeing - سالخوردهNuclear respiratory factor 1 - عامل تنفسی هسته ای 1mitochondrial transcription factor A - عامل رونویسی میتوکندری Adermal fibroblasts - فیبروبلاست های پوستیMitochondrial - میتوکندریاfalse discovery rate - میزان کشف کاذبmammalian target of rapamycin - هدف پستانداران رپامایسینarbitrary units - واحد دلخواهMitochondrial membrane potential - پتانسیل غشای میتوکندریcarbonyl cyanide m-chlorophenyl hydrazone - کربونیل سیانید m-کلروفنیل هیدرازونReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Extrinsic skin ageing converges on the dermis, a post-mitotic tissue compartment consisting of extracellular matrix and long-lived fibroblasts prone to damage accumulation and maladaptation. Aged human fibroblasts exhibit mitochondrial and nuclear dysfunctions, which may be a cause or consequence of ageing. We report on a systematic study of human dermal fibroblasts retrieved from female donors aged 20-67 years and analysed ex vivo at low population doubling precluding replicative senescence. According to gene set enrichment analysis of genome wide array data, the most prominent age-associated change of the transcriptome was decreased expression of mitochondrial genes. Consistent with that, mitochondrial content and cell proliferation declined with donor age. This was associated with upregulation of AMP-dependent protein kinase (AMPK), increased mRNA levels of PPARγ-coactivator 1α (PGC1A) and decreased levels of NAD+-dependent deacetylase sirtuin 1. In the old cells the PGC1A-mediated mito-biogenetic response to direct AMPK-stimulation by AICAR was undiminished, while the PGC1A-independent mito-biogenetic response to starvation was attenuated and accompanied by increased ROS-production. In summary, these observations suggest an age-associated decline in PGC1A-independent mito-biogenesis, which is insufficiently compensated by upregulation of the AMPK/PGC1A-axis leading under baseline conditions to decreased mitochondrial content and reductive overload of residual respiratory capacity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 56, August 2014, Pages 59-68
Journal: Experimental Gerontology - Volume 56, August 2014, Pages 59-68
نویسندگان
Faiza Kalfalah, Stefan Sobek, Beatrice Bornholz, Christine Götz-Rösch, Julia Tigges, Ellen Fritsche, Jean Krutmann, Karl Köhrer, René Deenen, Sebastian Ohse, Melanie Boerries, Hauke Busch, Fritz Boege,