Thioredoxin down-regulation in the cytosol in thioredoxin 2 transgenic mice did not have beneficial effects to extend lifespan in male C57BL/6 mice

Background: This study was conducted to test the effects of thioredoxin (Trx)1 down-regulation in Trx2 transgenic [Tg(TXN2)+/0] mice on lifespan and age-related diseases. Our previous study with Tg(TXN2)+/0 mice showed that mitochondrial Trx overexpression produced minimal life-extending effects with a slightly elevated severity of lymphoma and another study with a limited number of Trx1KO mice showed that there was a slight reduction of neoplastic lesions. Thus, this study was aimed to test if reduced Trx1 expression in combination with elevated Trx2 has beneficial effects on lifespan in mice by attenuating age-related diseases, specifically cancer. Methods: Trx2 hemizygous transgenic and Trx1 heterozygous knockout mice [Tg(TXN2)+/0 x Trx1KO] were generated for survival and cross-sectional pathology experiments. Results: Tg(TXN2)+/0 x Trx1KO mice showed significantly higher (approximately 1.5- to 3-fold) Trx2 levels and significantly less (approximately 50% less) Trx1 levels in all of the tissues we examined compared to wildtype (WT) littermates. Trx1 down-regulation along with Trx2 overexpression did not change the levels of glutathione or other major antioxidant enzymes. Male Tg(TXN2)+/0 x Trx1KO mice demonstrated only a slight extension of lifespan in the early part of life and no significant effects on the later part of life were observed,which was similar to our previous study with Tg(TXN2)+/0 mice. Tg(TXN2)+/0 x Trx1KO mice had similar tumor burden, disease burden, incidence and severity of lymphoma, and severity of glomerulonephritis compared to WT mice at 22-26 months. Conclusions: Our findings suggest that the combined Trx down-regulation in cytosol along with upregulation in mitochondria of Tg(TXN2)+/0 x Trx1KO mice did not provide beneficial effects on aging, i.e., extend the lifespan or reduce age-related pathology compared to WT mice. Keywords: Thioredoxin, transgenic mouse, knockout mouse, aging, cancer

Assessment of loss of health of the population of an older age group

Introduction. The problems of preserving the health of the older generation are especially significant for society and determine the need to search for key indices of medical and social well-being. The purpose of the study is to develop a method for assessing the health losses of the population of the older age group and to test using the example of the Siberian Federal District. Material and methods. For a comprehensive assessment, the following groups of indices were used: the life expectancy, mortality, morbidity, chronic diseases, cumulative disability in group 60+. An integrated assessment of health by the sum of normalized indices by the average value for the Siberian Federal District (NP) is proposed. There was using cluster analysis. Results. Dysfunctional territories (NP≥3) include: Altai Territory, Altai Republic, Irkutsk Region. 4 clusters were identified, of which the 1st cluster has the highest mortality and morbidity rates. Levels of life expectancy, the coefficient of chronicity of diseases in the IV cluster is higher than in II cluster. Cluster III is characterized by the lowest mortality, morbidity, against the background of minimal life expectancy and high cumulative disability. Discussion. The value of the proposed method is limited by the completeness of information on indices of health loss, the different availability of medical care in the territories. Conclusion. The proposed approach to assessing health losses in a group of older people has shown medical and demographic problems in the Siberian Federal District to be very different, which determines a differentiated approach to maintaining public health.

Life Balance-Considered Matching Optimization Method for Remanufactured Parts

In the manufacturing process of remanufactured products, balancing the life between their components is one of the important measures to achieve full utilization of waste components and sustainable economic development. In order to prolong the life cycle of remanufactured products and increase the life of parts and components, a life balance-considered matching optimization method is proposed for remanufactured parts in the process of components matching. By comprehensively considering the life matching degree of remanufactured parts and the matching success rate, a life balance-considered matching optimization model is established for remanufactured parts. We adopted an improved ant colony algorithm to solve the proposed matching model to get multiple sets of optimal component combinations with minimal life deviations between component combinations. The correctness of the model and the effectiveness of the algorithm are verified by taking the gear reducer component matching process as an example.

Designing an early failure indicator channel for an in-tank hydrogen valve via a fatigue-based approach

This study introduced a fatigue-based approach to design and implement an indicator channel into an in-tank hydrogen valve. It was aimed at providing a mean to point out multiple early valve's damages. To achieve the goal, the study was proposed to handle via three main phases. They included (i) the risk point determinations, (ii) the new valve design and the crack nucleation life estimations, as well as (iii) the simplified crack growth analyses. The obtained results firstly highlighted the construction of the test channel (TC), whose branches were located close to the predicted damage's sites. The damages could be identified either when a crack reaches the TC (then forms a leakage) or indirectly via the crack propagations’ correlation. The results also pointed out that the TC-implemented valve could perform as similarly as the non-TC one in the non-treated condition. More importantly, this new structure was proved to have a capacity of satisfying the required minimal life of 1.5E5 cycles, depending on the combined uses of the specific material and the pre-treatment, among those considered. In addition, the results emphasized the complexity of the TC that could not be formed by the traditional manufacturing process. Hence, direct metal laser sintering was proposed for the associated prototype and the final TC was issued based on the fundamental requirements of the technique. Finally, it was suggested that practical experiments should essentially be carried out to yield more evidence to support the demonstrated results.

Autocatalytic Networks at the Basis of Life’s Origin and Organization

Life is more than the sum of its constituent molecules. Living systems depend on a particular chemical organization, i.e., the ways in which their constituent molecules interact and cooperate with each other through catalyzed chemical reactions. Several abstract models of minimal life, based on this idea of chemical organization and also in the context of the origin of life, were developed independently in the 1960s and 1970s. These models include hypercycles, chemotons, autopoietic systems, (M,R)-systems, and autocatalytic sets. We briefly compare these various models, and then focus more specifically on the concept of autocatalytic sets and their mathematical formalization, RAF theory. We argue that autocatalytic sets are a necessary (although not sufficient) condition for life-like behavior. We then elaborate on the suggestion that simple inorganic molecules like metals and minerals may have been the earliest catalysts in the formation of prebiotic autocatalytic sets, and how RAF theory may also be applied to systems beyond chemistry, such as ecology, economics, and cognition.

Generating minimal living systems from non-living materials and increasing their evolutionary abilities

We review lessons learned about evolutionary transitions from a bottom-up construction of minimal life. We use a particular systemic protocell design process as a starting point for exploring two fundamental questions: (i) how may minimal living systems emerge from non-living materials? and (ii) how may minimal living systems support increasingly more evolutionary richness? Under (i), we present what has been accomplished so far and discuss the remaining open challenges and their possible solutions. Under (ii), we present a design principle we have used successfully both for our computational and experimental protocellular investigations, and we conjecture how this design principle can be extended for enhancing the evolutionary potential for a wide range of systems. This article is part of the themed issue ‘The major synthetic evolutionary transitions’.