Cellular senescence in vitro and organismal ageing

Replicative ageing of fibroblasts has often been used as a model for organismal ageing. The general assumption that the ageing process is mirrored by cellular senescence in vitro is based on lower replicative capacity of human fibroblasts from donors of higher chronological age, but these inverse relations have not been reported unequivocally. The relation between chronological age and fibroblast growth characteristics was assessed in nonagenarian subjects of the Leiden 85+ Study. A high remaining replicative capacity impressively showed that even in the very elderly a crucial number of cells with high mitotic capacity are left to give rise to fibroblast strains with the capacity for more than 100 population doublings. During the course of fibroblast growth in vitro, beta-galactosidase activity has been shown to be a reliable biomarker for replicative senescence. In myoblast cultures the relation between mixed cultures and clonal cultures was studied, showing marked heterogeneity between clonal cultures that all had a significantly lower replicative capacity when compared to mixed cultures, indicating heterogeneity of cells within one tissue compartment in their in vivo history. In a formal review on the replicative capacity of fibroblasts from patients suffering from accelerated ageing syndromes, age related diseases and donor age it was found that except for premature ageing syndromes, the replicative capacity of fibroblasts in vitro does not mirror key characteristics of human life histories.UBL - phd migration 201

Sustainability assessment of housing developments : a new methodology

Afin de combattre la dégradation rapide des écosystèmes mondiaux ainsi que l'épuisement des ressources naturelles, les gouvernements et les autorités de planification recherchent des formes de développement plus durables. La nécessité d'évaluer la «soutenabilité» des propositions de développement est ainsi de grande importance pour la politique et les décideurs. Cependant, des méthodes efficaces pour évaluer la durabilité globale des développements de logement (proposés ou existants) ne sont pas encore établies. Les objectifs de ces recherches adressent ce problème en présentant une nouvelle méthodologie conçue pour évaluer la durabilité des systèmes complexes de développement de logement. Une méthode pour évaluer des indicateurs de durabilité sur une «échelle de soutenabilité», basée sur des centiles d'une population avec l'utilisation de ressource audessus d'un seuil soutenable, a été développée. Cette méthode a été couplée à une technique pour modéliser les systèmes de développement complexes de logement en utilisant la simulation multi-agent. La méthodologie a été mise en pratique dans un cas d'étude du groupe de logements, Christie Walk, situé au centre-ville d'Adélaïde en Australie. Les résultats de cette évaluation ont demontré que Christie Walk est plus soutenable que la plupart de la zone métropolitaine d'Adélaïde. Les resultats des analyses de scénario montrent aussi l'importance d'une bonne infrastructure et conception des développements pour réduire les impacts du comportement humain sur la durabilité des logements. On envisage que cette nouvelle méthodologie, qui couple l'évaluation de la durabilité avec une technique de modélisation integrée, fournira une base fondementale pour résoudre plusieurs des défis auxquels font actuellement face les chercheurs en développement durable, les décideurs et les autorités de planification des environnements urbains en Australie et dans le reste du monde. / In order to combat the rapid degradation of the world's ecosystems and depletion of natural resources, governments and planning authorities are searching for more sustainable forms of development. The need to assess the sustainability of development proposals is thus of great importance to policy and decision makers. However, effective methods of assessing the overall sustainability of housing developments (proposed or existing) have yet to be established. This research aims to address this problem by presenting a new methodology to assess the sustainability of housing development systems. The methodology uses indicators with a common Sustainability Scale which is derived from percentiles of a population with resource use above a predetermined sustainable level, and has been coupled with a technique for modelling complex housing development systems using multiagent based simulation. The methodology was shown to be operational in the case study application of the Christie Walk housing development in inner-city Adelaide, Australia. The results of the assessment showed that the development compared favourably to the rest of the Adelaide metropolitan area. The case study also highlighted, through behavioural scenario analyses, the importance of good infrastructure and design in reducing the impacts of human behaviour on housing development sustainability. It is envisaged that this new methodology of combining sustainability assessment with an integrated modelling technique will provide the basis for a solution to many of the challenges currently facing sustainability researchers, policy makers and planning authorities of urban environments both in Australia and world wide

Age-related DNA methylation changes: Potential impact on skeletal muscle aging in humans

Human aging is accompanied by a decline in muscle mass and muscle function, which is commonly referred to as sarcopenia. Sarcopenia is associated with detrimental clinical outcomes, such as a reduced quality of life, frailty, an increased risk of falls, fractures, hospitalization, and mortality. The exact underlying mechanisms of sarcopenia are poorly delineated and the molecular mechanisms driving the development and progression of this disorder remain to be uncovered. Previous studies have described age-related differences in gene expression, with one study identifying an age-specific expression signature of sarcopenia, but little is known about the influence of epigenetics, and specially of DNA methylation, in its pathogenesis. In this review, we will focus on the available knowledge in literature on the characterization of DNA methylation profiles during skeletal muscle aging and the possible impact of physical activity and nutrition. We will consider the possible use of the recently developed DNA methylation-based biomarkers of aging called epigenetic clocks in the assessment of physical performance in older individuals. Finally, we will discuss limitations and future directions of this field

Recovery Map for Fermionic Gaussian Channels

A recovery map effectively cancels the action of a quantum operation to a partial or full extent. We study the Petz recovery map in the case where the quantum channel and input states are fermionic and Gaussian. Gaussian states are convenient because they are totally determined by their covariance matrix and because they form a closed set under so-called Gaussian channels. Using a Grassmann representation of fermionic Gaussian maps, we show that the Petz recovery map is also Gaussian and determine it explicitly in terms of the covariance matrix of the reference state and the data of the channel. As a by-product, we obtain a formula for the fidelity between two fermionic Gaussian states. We also discuss subtleties arising from the singularities of the involved matrices.Comment: 13 pages and 11 pages of appendices. Updated references and footnotes in v2. Updated for a new paragraph of twisted recovery map and change of format in v

Scaling analysis of a divergent prefactor in the metastable lifetime of a square-lattice Ising ferromagnet at low temperatures

We examine a square-lattice nearest-neighbor Ising quantum ferromagnet coupled to $d$-dimensional phonon baths. Using the density-matrix equation, we calculate the transition rates between configurations, which determines the specific dynamic. Applying the calculated stochastic dynamic in Monte Carlo simulations, we measure the lifetimes of the metastable state. As the magnetic field approaches $|H|/J=2$ at low temperatures, the lifetime prefactor diverges because the transition rates between certain configurations approaches zero under these conditions. Near $|H|/J=2$ and zero temperature, the divergent prefactor shows scaling behavior as a function of the field, temperature, and the dimension of the phonon baths. With proper scaling, the simulation data at different temperatures and for different dimensions of the baths collapse well onto two master curves, one for $|H|/J>2$ and one for $|H|/J<2$.Comment: published versio

Sensory reweighting of proprioceptive input during balance control in healthy elderly

Sensory (re)weighting is the automated and unconscious process of combining sensory inputs, e.g. proprioception, graviception and vision, during human balance control. Typically reliable sensory inputs are weighted more than unreliable and noisy sensory inputs, to prevent deterioration of human balance control. Malfunctioning of sensory reweighting may be an important determinant of balance deficits in elderly with the consequence of falls. In this study we compared sensory (re)weighting of prioprioceptive input of the ankle joints, as one of the available sensory inputs, in healthy young versus healthy elderly during upright stance. Ten healthy young (aged 20-30 years) and ten healthy elderly (aged 75-80 years) were asked to maintain balance while proprioceptive input of each ankle was perturbed by rotations of the support surfaces around the ankle axes. Support surface rotations were applied with specific frequency content and increasing perturbation amplitude over trials. Body sway and reactive ankle torques were recorded. The sensitivity of the ankle torques to perturbation amplitude was determined using system identification techniques. The gain of a sensitivity function describes the ratio of perturbation amplitude and response amplitude as a function of frequency. Overall, elderly had a significant higher gain of the sensitivity function than young subjects. Increasing amplitude of the sensory perturbation resulted in a significant decrease of the gain of the sensitivity function from the perturbation amplitude to the ankle torque. Significant frequency-dependent interactions between group and perturbation amplitude could be established. A significant higher ankle torque sensitivity to perturbations indicates that elderly rely more strongly on proprioceptive input to maintain balance compared to younger subjects. Different reactions of elderly versus young subjects to perturbation amplitudes are indicative of differences in sensory reweighting. Results are important to understand interplay between available sensory inputs in balance and falling

Pulse transit time as a proxy for vasoconstriction in younger and older adults

Objectives: Changes of vasoconstriction may be measured non-invasively using pulse transit time. This study assessed the sensitivity, test-retest reliability and validity of pulse transit time during vasoconstriction provocation and active standing, and the predictive value of pulse transit time for blood pressure drop. Methods: Fifty-five younger (age 70 years) underwent electrocardiography, wrist and finger photoplethysmography and continuous blood pressure and total peripheral resistance measurements during vasoconstriction provocation using a cold pressor test (21 younger adults), or active stand tests (all other participants). Pulse transit tim

Pulse transit time as a proxy for vasoconstriction in younger and older adults

Objectives: Changes of vasoconstriction may be measured non-invasively using pulse transit time. This study assessed the sensitivity, test-retest reliability and validity of pulse transit time during vasoconstriction provocation and active standing, and the predictive value of pulse transit time for blood pressure drop. Methods: Fifty-five younger (age 70 years) underwent electrocardiography, wrist and finger photoplethysmography and continuous blood pressure and total peripheral resistance measurements during vasoconstriction provocation using a cold pressor test (21 younger adults), or active stand tests (all other participants). Pulse transit tim

Five-loop renormalization-group expansions for the three-dimensional n-vector cubic model and critical exponents for impure Ising systems

The renormalization-group (RG) functions for the three-dimensional n-vector cubic model are calculated in the five-loop approximation. High-precision numerical estimates for the asymptotic critical exponents of the three-dimensional impure Ising systems are extracted from the five-loop RG series by means of the Pade-Borel-Leroy resummation under n = 0. These exponents are found to be: \gamma = 1.325 +/- 0.003, \eta = 0.025 +/- 0.01, \nu = 0.671 +/- 0.005, \alpha = - 0.0125 +/- 0.008, \beta = 0.344 +/- 0.006. For the correction-to-scaling exponent, the less accurate estimate \omega = 0.32 +/- 0.06 is obtained.Comment: 11 pages, LaTeX, no figures, published versio