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Human genetic diseases that resemble accelerated aging provide useful models for gerontologists. They combine known single-gene mutations with deficits in selected tissues that are reminiscent of changes seen during normal aging. Here, we describe recent progress toward linking molecular and cellular changes with the phenotype seen in two of these disorders. One in particular, Werner syndrome, provides evidence to support the hypothesis that the senescence of somatic cells may be a causal agent of normal aging.

For a monolayer of 2,3-di-phytanyl-sn-glycerol-1-tetraethylene glycol-D,L-a-lipoic acid ester lipid (DPTL) self-assembled (SAM) at a gold electrode surface we propose a new method to determine the charge number per adsorbed molecule and the packing density (area per molecule) in the monolayer. The method relies on chronocoulometry to measure the charge density at the SAM covered gold electrode surface. Two series of measurements have to be performed. In the first series, charge densities are measured for a monolayer transferred from the air-solution to the metal-solution interface using the Langmuir-Blodgett (LB) technique. This series of measurements allows one to determine charge numbers per adsorbed DPTL molecule. The second series is performed using a gold electrode covered with a self-assembled monolayer. The charge densities obtained in this series are then used to calculate the packing density with the help of charge numbers per adsorbed DPTL determined in the first series. The area per adsorbed molecule determined by the new method was compared to the area per molecule determined by the popular reductive desorption method. The molecular area determined with the new method is about 20% larger than the area calculated from the van der Waals model, which is a physically reasonable result. In contrast, the popular reductive desorption method gives an area per molecule 20% lower than the minimum estimated based on a van der Waals model. This is a physically unreasonable result. It is also shown that the charge numbers per adsorbed molecule depend on the electrode potential and may assume values smaller than the number of electrons participating in the reductive desorption step. An explanation of the origin of the "partial charge numbers" is provided. We recommend the new method be used in future studies of thiol adsorption at metal surfaces.

Cellular senescence is now considered as a major mechanism in the development and progression of various diseases and this may include metabolic diseases such as obesity and type-2 diabetes. The presence of obesity and diabetes is a major risk factor in the development of additional health conditions, such as cardiovascular disease, kidney disease and cancer. Since senescent cells can drive disease development, obesity and diabetes can potentially create an environment that accelerates cell senescence within other tissues of the body. This can consequently manifest as age-related biological impairments and secondary diseases. Cell senescence in cell types linked with obesity and diabetes, namely adipocytes and pancreatic beta cells will be explored, followed by a discussion on the role of obesity and diabetes in accelerating ageing through induction of premature cell senescence mediated by high glucose levels and oxidised low-density lipoproteins. Particular emphasis will be placed on accelerated cell senescence in endothelial progenitor cells, endothelial cells and vascular smooth muscle cells with relation to cardiovascular disease and proximal tubular cells with relation to kidney disease. A summary of the potential strategies for therapeutically targeting senescent cells for improving health is also presented.

BackgroundAltered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence.ResultsTreatment with resveralogues was associated with altered splicing factor expression and rescue of multiple features of senescence. This rescue was independent of cell cycle traverse and also independent of SIRT1, SASP modulation or senolysis. Under growth permissive conditions, cells demonstrating restored splicing factor expression also demonstrated increased telomere length, re-entered cell cycle and resumed proliferation. These phenomena were also influenced by ERK antagonists and agonists.ConclusionsThis is the first demonstration that moderation of splicing factor levels is associated with reversal of cellular senescence in human primary fibroblasts. Small molecule modulators of such targets may therefore represent promising novel anti-degenerative therapies.Electronic supplementary materialThe online version of this article (10.1186/s12860-017-0147-7) contains supplementary material, which is available to authorized users.

Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) has been applied to determine the conformation, orientation, and hydration of a monolayer of 2,3-di-O-phytanyl-sn-glycerol-1-tetraethylene glycol-dl-alpha-lipoic acid ester (DPTL) self-assembled at a gold electrode surface. This Archaea analogue thiolipid has been recently employed to build tethered lipid bilayers. By synthesizing DPT(d16)L, a DPTL molecule with a deuterium substituted tetraethylene glycol spacer, it was possible to differentiate the C-H stretch vibrations of the phytanyl chains from the tetraethylene glycol spacer and acquire the characteristic IR spectra for the chains, spacer, and lipoic acid headgroup separately. Our results show that the structure of the monolayer displays remarkable stability in a broad range of electrode potentials and that the phytanyl chains remain in a liquid crystalline state. The tetraethylene glycol chains are coiled, and the IR spectrum for this region shows that it is in the disordered state. The most significant result of this study is the information that in contrast to expectations the spacer region is poorly hydrated. Our results have implications for the design of a tethered lipid membrane based on this thiolipid.

Werner syndrome is a rare, autosomal, recessive condition that is frequently studied as a model of some