Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway

Either calorie restriction, loss of function of the nutrient-dependent PKA or TOR/SCH9 pathways, or activation of stress defences improves longevity in different eukaryotes. However, the molecular links between glucose depletion, nutrient-dependent pathways and stress responses are unknown. Here we show that either calorie restriction or inactivation of nutrient-dependent pathways induces life-span extension in fission yeast, and that such effect is dependent on the activation of the stress-dependent Sty1 MAP kinase. During transition to stationary phase in glucose-limiting conditions, Sty1 becomes activated and triggers a transcriptional stress program, whereas such activation does not occur under glucose-rich conditions. Deletion of the genes coding for the SCH9-homologue Sck2 or the Pka1 kinases, or mutations leading to constitutive activation of the Sty1 stress pathway increase life span under glucose-rich conditions, and importantly such beneficial effects depend ultimately on Sty1. Furthermore, cells lacking Pka1 display enhanced oxygen consumption and Sty1 activation under glucose-rich conditions. We conclude that calorie restriction favours oxidative metabolism, reactive oxygen species production and Sty1 MAP kinase activation, and this stress pathway favours life-span extension.

Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production

Single-gene mutations that extend lifespan provide valuable tools for the exploration of the molecular basis for age-related changes in cell and tissue function and for the pathophysiology of age-dependent diseases. We show here that mice homozygous for loss-of-function mutations at the Pit1 (Snell dwarf) locus show a >40% increase in mean and maximal longevity on the relatively long-lived (C3H/HeJ × DW/J)F1 background. Mutant dwJ/dw animals show delays in age-dependent collagen cross-linking and in six age-sensitive indices of immune system status. These findings thus demonstrate that a single gene can control maximum lifespan and the timing of both cellular and extracellular senescence in a mammal. Pituitary transplantation into dwarf mice does not reverse the lifespan effect, suggesting that the effect is not due to lowered prolactin levels. In contrast, homozygosity for the Ghrhrlit mutation, which like the Pit1dw mutation lowers plasma growth hormone levels, does lead to a significant increase in longevity. Male Snell dwarf mice, unlike calorically restricted mice, become obese and exhibit proportionately high leptin levels in old age, showing that their exceptional longevity is not simply due to alterations in adiposity per se. Further studies of the Pit1dw mutant, and the closely related, long-lived Prop-1df (Ames dwarf) mutant, should provide new insights into the hormonal regulation of senescence, longevity, and late life disease.

Strong and weak lifespan extension: What is most feasible and likely?

Recent advances in biomedical science indicate that it may eventually be possible to intervene in the biological process of human ageing. This paper overviews the current state of the science of lifespan extension and promising future directions. It is uncertain whether 'strong' lifespan extension - the extension of human life beyond the maximum 122 years so far observed - will become a reality. It is more likely that cumulative effects of numerous scientific and biomedical advances in the treatment of common disease will produce 'weak' lifespan extension - the extension of average life expectancy. The practical application of molecular, genetic and nanomaterials research may also lead to advances in life expectancy. It is not too early to begin to consider the policy implications of either form of lifespan extension.

What does the community think about lifespan extension technologies? The need for an empirical base for ethical and policy debates

Objectives: This paper examines public understandings of possibilities for increasing life expectancy, interest in taking up lifespan-extending interventions, and motivations influencing these intentions. Methods: Structured interviews were conducted with 31 adults, aged 50 and over. Results: Participants believed that technological advances would increase life expectancy but questioned the value of quantity over quality of life. Life in itself was not considered valuable without the ability to put it to good use. Participants would not use technologies to extend their own lifespan unless the result would also enhance their health. Conclusions: These findings may not be generalisable to the general public but they provide the first empirical evidence on the plausibility of common assumptions about public interest in 'anti-ageing' interventions. Surveys of the views of representative samples of the population are needed to inform the development of a research agenda on the ethical, legal and social implications of lifespan extension.

Dietary restriction affects lifespan but not cognitive aging in Drosophila melanogaster.

Summary Dietary restriction extends lifespan in a wide variety of animals, including Drosophila, but its relationship to functional and cognitive aging is unclear. Here, we study the effects of dietary yeast content on fly performance in an aversive learning task (association between odor and mechanical shock). Learning performance declined at old age, but 50-day-old dietary-restricted flies learned as poorly as equal-aged flies maintained on yeast-rich diet, even though the former lived on average 9 days (14%) longer. Furthermore, at the middle age of 21 days, flies on low-yeast diets showed poorer short-term (5 min) memory than flies on rich diet. In contrast, dietary restriction enhanced 60-min memory of young (5 days old) flies. Thus, while dietary restriction had complex effects on learning performance in young to middle-aged flies, it did not attenuate aging-related decline of aversive learning performance. These results are consistent with the hypothesis that, in Drosophila, dietary restriction reduces mortality and thus leads to lifespan extension, but does not affect the rate with which somatic damage relevant for cognitive performance accumulates with age.

Changes of telomere length cause reciprocal changes in the lifespan of mother cells in Saccharomyces cerevisiae

Budding yeast cells divide asymmetrically, giving rise to a mother and its daughter. Mother cells have a limited division potential, called their lifespan, which ends in proliferation-arrest and lysis. In this report we mutate telomerase in Saccharomyces cerevisiae to shorten telomeres and show that, rather than shortening lifespan, this leads to a significant extension in lifespan. This extension requires the product of the SIR3 gene, an essential component of the silencing machinery which binds to telomeres. In contrast, longer telomeres in a genotypically wild-type strain lead to a decrease in lifespan. These findings suggest that the length of telomeres dictates the lifespan by regulating the amount of the silencing machinery available to nontelomeric locations in the yeast genome.

An Extension of the Invariance Principle for a Class of Differential Equations with Finite Delay

An extension of the uniform invariance principle for ordinary differential equations with finite delay is developed. The uniform invariance principle allows the derivative of the auxiliary scalar function V to be positive in some bounded sets of the state space while the classical invariance principle assumes that. V <= 0. As a consequence, the uniform invariance principle can deal with a larger class of problems. The main difficulty to prove an invariance principle for functional differential equations is the fact that flows are defined on an infinite dimensional space and, in such spaces, bounded solutions may not be precompact. This difficulty is overcome by imposing the vector field taking bounded sets into bounded sets.

Evaluation of Cadaveric Renal Vein Lengths and Their Extension Loss with Three Types of Ligature and Section

Background and Purpose: The right kidney has been less frequently used in live donor nephrectomy, because of the shorter length of the right renal vein (RRV) that is associated with technical difficulties and higher rates of venous thrombosis. In live open donor or deceased donor transplant nephrectomy, an additional cuff of the inferior vena cava is usually removed, but this is a more difficult and risky maneuver in laparoscopic nephrectomy. For this reason, laparoscopic right nephrectomy (LRN) for renal transplantation (RT) is not frequently performed in most medical institutions. We evaluate the difference between RRV and left renal vein (LRV) lengths in cadavers, as harvested for RT by three clamping methods. Our objective was to obtain information that could clarify when LRN for RT should be encouraged or avoided with regard to conventional surgery. Materials and Methods: Ninety adult fresh unfrozen cadavers were randomly divided into three groups of 30, according to the clamping device used: Satinsky, stapler, and Hem-o-lok clip. The abdominal viscera were removed through a median xyphopubic incision, and the veins were measured on the bench. Two lateral limits were used: The renal hilum and the tangential line of the renal poles. As for medial limits, the inferior vena cava or the laparoscopic clipping device on the RRV were used on the right side, while on the LRV, the medial border of the emergence of the adrenal vein was considered. After section of the renal vein, a slight traction of the extremity was applied for the measurement. All measurements were obtained three times using a metallic millimetric ruler, and the arithmetic mean was considered. The chi-square, one-way analysis of variance, and paired t tests were used for statistical analysis. Statistical significance was accepted at P <= 0.05. Results: The groups of cadavers were homogeneous in demographic characteristics. Regardless of the clamping method and considering the useful length of the LRV, the RRV was statistically smaller. The evaluation of the vein length did not depend on the lateral limit considered. Independent of the clamping method, on both sides, the lengths after the vein section were larger than before the section, a fact attributed to traction. Use of a stapler and a single Hem-o-lok presented the same waste of vein length on the right side. On average, the RRV was 13.7% shorter than the LRV. Conclusions: With the wide acceptance of laparoscopic live donor nephrectomy, the length difference between the veins of both kidneys is an important issue, and the right kidney is therefore used less than the left, compared with conventional surgery. This article represents the first step to quantify the anatomic length of renal veins in different situations. Certainly, more imagenologic or surgical studies should be carried out before decisions can be made for better selection of patients for LRN.

DJKM ALGEBRAS I: THEIR UNIVERSAL CENTRAL EXTENSION

The purpose of this paper is to explicitly describe in terms of generators and relations the universal central extension of the infinite dimensional Lie algebra, g circle times C[t, t(-1), u vertical bar u(2) = (t(2) - b(2))(t(2) - c(2))], appearing in the work of Date, Jimbo, Kashiwara and Miwa in their study of integrable systems arising from the Landau-Lifshitz differential equation.

Experimental analysis of active-passive vibration control using viscoelastic materials and extension and shear piezoelectric actuators

Hybrid active-passive damping treatments combine the reliability, low cost and robustness of viscoelastic damping treatments and the high-performance, modal selective and adaptive piezoelectric active control. Numerous hybrid damping treatments have been reported in the literature. They differ mainly by the relative positions of viscoelastic treatments, sensors and piezoelectric actuators. In this work we present an experimental analysis of three active-passive damping design configurations applied to a cantilever beam. In particular, two design configurations based on the extension mode of piezoelectric actuators combined with viscoelastic constrained layer damping treatments and one design configuration with shear piezoelectric actuators embedded in a sandwich beam with viscoelastic core are analyzed. For comparison purposes, a purely active design configuration with an extension piezoelectric actuator bonded to an elastic beam is also analyzed. The active-passive damping performance of the four design configurations is compared. Results show that active-passive design configurations provide more reliable and wider-range damping performance than the purely active configuration.

Numerical modeling of ductile crack extension in high pressure pipelines with longitudinal flaws

This study examines the applicability of a micromechanics approach based upon the computational cell methodology incorporating the Gurson-Tvergaard (GT) model and the CTOA criterion to describe ductile crack extension of longitudinal crack-like defects in high pressure pipeline steels. A central focus is to gain additional insight into the effectiveness and limitations of both approaches to describe crack growth response and to predict the burst pressure for the tested cracked pipes. A verification study conducted on burst testing of large-diameter, precracked pipe specimens with varying crack depth to thickness ratio (a/t) shows the potential predictive capability of the cell approach even though both the CT model and the CTOA criterion appear to depend on defect geometry. Overall, the results presented here lend additional support for further developments in the cell methodology as a valid engineering tool for integrity assessments of pipelines with axial defects. (C) 2011 Elsevier Ltd. All rights reserved,

An extension of the Pitzer equation for the excess Gibbs energy of aqueous electrolyte systems to aqueous polyelectrolyte solutions

Pitzer`s equation for the excess Gibbs energy of aqueous solutions of low-molecular electrolytes is extended to aqueous solutions of polyelectrolytes. The model retains the original form of Pitzer`s model (combining a long-range term, based on the Debye-Huckel equation, with a short-range term similar to the virial equation where the second osmotic virial coefficient depends on the ionic strength). The extension consists of two parts: at first, it is assumed that a constant fraction of the monomer units of the polyelectrolyte is dissociated, i.e., that fraction does not depend on the concentration of the polyelectrolyte, and at second, a modified expression for the ionic strength (wherein each charged monomer group is taken into account individually) is introduced. This modification is to account for the presence of charged polyelectrolyte chains, which cannot be regarded as punctual charges. The resulting equation was used to correlate osmotic coefficient data of aqueous solutions of a single polyelectrolyte as well as of binary mixtures of a single polyelectrolyte and a salt with low-molecular weight. It was additionally applied to correlate liquid-liquid equilibrium data of some aqueous two-phase systems that might form when a polyelectrolyte and another hydrophilic but neutral polymer are simultaneously dissolved in water. A good agreement between the experimental data and the correlation result is observed for all investigated systems. (c) 2008 Elsevier B.V. All rights reserved.

Ciratefi: An RST-invariant template matching with extension to color images

Template matching is a technique widely used for finding patterns in digital images. A good template matching should be able to detect template instances that have undergone geometric transformations. In this paper, we proposed a grayscale template matching algorithm named Ciratefi, invariant to rotation, scale, translation, brightness and contrast and its extension to color images. We introduce CSSIM (color structural similarity) for comparing the similarity of two color image patches and use it in our algorithm. We also describe a scheme to determine automatically the appropriate parameters of our algorithm and use pyramidal structure to improve the scale invariance. We conducted several experiments to compare grayscale and color Ciratefis with SIFT, C-color-SIFT and EasyMatch algorithms in many different situations. The results attest that grayscale and color Ciratefis are more accurate than the compared algorithms and that color-Ciratefi outperforms grayscale Ciratefi most of the time. However, Ciratefi is slower than the other algorithms.

Extension of a Recent Method for Obtaining Exact Solutions of the Bruce and Klute Equation

A method based on a specific power-law relationship between the hydraulic head and the Boltzmann variable was recently presented. We generalized this relationship to a range of powers and extended the solution to include the saturated zone. As a result, the new solution satisfies the Bruce and Klute equation exactly.