Abstract
The molecular processes of aging are very heterogenic and not fully understood. Studies on rare progeria syndromes, which display an accelerated progression of physiological aging, can help to get a better understanding. Pseudoxanthoma elasticum (PXE) caused by mutations in the ATP-binding cassette sub-family C member 6 (ABCC6) gene shares some molecular characteristics with such premature aging diseases. Thus, this is the first study trying to broaden the knowledge of aging processes in PXE patients. In this study, we investigated aging associated biomarkers in primary human dermal fibroblasts and sera from PXE patients compared to healthy controls. Determination of serum concentrations of the aging biomarkers eotaxin-1 (CCL11), growth differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF1) showed no significant differences between PXE patients and healthy controls. Insulin-like growth factor binding protein 3 (IGFBP3) showed a significant increase in serum concentrations of PXE patients older than 45 years compared to the appropriate control group. Tissue specific gene expression of GDF11 and IGFBP3 were significantly decreased in fibroblasts from PXE patients compared to normal human dermal fibroblasts (NHDF). IGFBP3 protein concentration in supernatants of fibroblasts from PXE patients were decreased compared to NHDF but did not reach statistical significance due to potential gender specific variations. The minor changes in concentration of circulating aging biomarkers in sera of PXE patients and the significant aberrant tissue specific expression seen for selected factors in PXE fibroblasts, suggests a link between ABCC6 deficiency and accelerated aging processes in affected peripheral tissues of PXE patients.
Highlights
Aging is a heterogeneous process which is characterized by a time-dependent decline of physiological functionality and integrity
Pseudoxanthoma elasticum (PXE) pathogenesis has just barely been discussed in the view of the fact that the clinical and molecular characteristics of PXE patients equal those seen in premature aging and premature aging syndromes
This study was performed to evaluate specific aging biomarkers in sera and fibroblasts from PXE patients to get insights into potential aging processes associated with an ATP-binding cassette subfamily C member 6 (ABCC6) deficiency in PXE patients
Summary
Aging is a heterogeneous process which is characterized by a time-dependent decline of physiological functionality and integrity. In many cases rare progeria syndromes like the Hutchinson-Gilford-progeria syndrome (HGPS) or related cell culture models displaying an accelerated aging process are used for gerontological studies [2,3,4]. Molecular studies showed that ABCC6 deficiency leads to aberrant pyrophosphate homeostasis, a known calcification inhibitor, characterized by a decreased plasma concentration [9,10,11,12]. It was further shown that the progression of HGPS can be decelerated by administration of statins and bisphosphonates [3] Studies demonstrated that this therapy could be beneficial for PXE the underlying molecular mechanisms remain unclear [1416]. It was shown that ABCC6 deficiency leads to an aberrant mitochondrial function and a loss of proteostasis characterized by abnormal expression and serum concentrations of matrix metalloproteinases [17, 18]. Mitochondrial dysfunction and a loss of proteostasis are known to play a role in physiological aging [19,20,21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
