The growing diversity of heritable skin diseases, a practical challenge to clinicians and dermato-nosologists alike, has nonetheless served as a rich source of insight into skin biology and disease mechanisms. I summarize below some key insights from the recent gene-driven phase of research on Werner syndrome, a heritable adult progeroid syndrome with prominent dermatologic features, constituti...

Microwave-assisted synthesis of the pyrazolyl ketone p38 MAPK inhibitor RO3201195 in 7 steps and 15% overall yield, and the comparison of its effect upon the proliferation of Werner Syndrome cells with a library of pyrazolyl ketones, strengthens the evidence that p38 MAPK inhibition plays a critical role in modulating premature cellular senescence in this progeroid syndrome and the reversal of ...

consequence of a stochastic process caused by the accumulative effect of damaged molecules. However, recent experimental evidences have extended this view and suggested that aging also requires active signaling programs for the maintenance of the aged state [1]. Beyond cell-autonomous alterations, age signals get systemic through changes in intercellular communication pathways [2]. The identifi...

Abstract. The aim of this paper is to study properties of sections of convex bodies with respect to different types of measures. We present a formula connecting the Minkowski functional of a convex symmetric body K with the measure of its sections. We apply this formula to study properties of general measures most of which were known before only in the case of the standard Lebesgue measure. We ...

Werner syndrome and Bloom syndrome result from defects in the RecQ helicases Werner (WRN) and Bloom (BLM), respectively, and display premature aging phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1-XPF DNA repair endonuclease. To gain insight into the origin of cellular senescence and human aging, we analyzed the dependence of sister chromatid exchange (SCE) frequ...

A valid method of studying age related degenerative pathologies is to study human genetic diseases that appear to accelerate many, though not necessarily all, features of the aging process. Such diseases are described as progeroid syndromes because of their possible relevance to many aspects of aging and age related disease. This article describes the recent progress made at the cellular and mo...

BubR1 insufficiency occurs with natural aging and induces progeroid phenotypes in both mice and children with mosaic variegated aneuploidy syndrome. In response to BubR1 insufficiency, skeletal muscle, fat, and lens tissue engage p19(Arf) to attenuate senescence and age-related deterioration. Here, we address how p19(Arf) exerts this caretaker role using BubR1 progeroid mice lacking p53 or its ...

Loss of WRN causes the genomic instability progeroid syndrome, Werner syndrome. WRN encodes a multifunctional nuclear protein with 3'-->5' exonuclease and 3'-->5' helicase activities. Linear plasmids with noncompatible ends introduced to Werner syndrome cells underwent extensive deletions at nonhomologous joining ends, particularly at the 3' protruding single-stranded end. This extensive deleti...