Anti-aging Research Articles

Melatonin as a natural anti-inflammatory and anti-oxidant therapy in the testis: a focus on infertility and aging†.

Melatonin is a pineal hormone that regulates testicular activity (i.e., steroidogenesis and spermatogenesis) through two complementary mechanisms, indirect effects exerted via the hypothalamic-adenohypophyseal axis and direct actions that take place on the different cell populations of the male gonad. The effects of increased age on the testis and the general mechanisms involved in testicular pathology leading to infertility are still only poorly understood. However, there is growing evidence that link testicular aging and idiopathic male infertility to local inflammatory and oxidative stress events. Because literature data strongly indicate that melatonin exhibits anti-inflammatory and anti-oxidant properties, this review focuses on the potential benefits exerted by this indoleamine at testicular level in male reproductive fertility and aging. Taking into account that the effects of melatonin supplementation on testicular function are currently being investigated, the overview covers not only promising prospects but also many questions concerning the future therapeutic value of this indoleamine as an anti-aging drug as well as in the management of cases of male infertility for which there are no medical treatments currently available.

Fmo-4 promotes longevity and stress resistance via ER to mitochondria calcium regulation in C. elegans.

Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that C. elegans fmo-2 promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five C. elegans FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that expression of C. elegans fmo-4 promotes lifespan extension and paraquat stress resistance downstream of both dietary restriction and inhibition of mTOR. We find that overexpression of fmo-4 in just the hypodermis is sufficient for these benefits, and that this expression significantly modifies the transcriptome. By analyzing changes in gene expression, we find that genes related to calcium signaling are significantly altered downstream of fmo-4 expression. Highlighting the importance of calcium homeostasis in this pathway, fmo-4 overexpressing animals are sensitive to thapsigargin, an ER stressor that inhibits calcium flux from the cytosol to the ER lumen. This calcium/ fmo-4 interaction is solidified by data showing that modulating intracellular calcium with either small molecules or genetics can change expression of fmo-4 and/or interact with fmo-4 to affect lifespan and stress resistance. Further analysis supports a pathway where fmo-4 modulates calcium homeostasis downstream of activating transcription factor-6 ( atf-6 ), whose knockdown induces and requires fmo-4 expression. Together, our data identify fmo-4 as a longevity- promoting gene whose actions interact with known longevity pathways and calcium homeostasis.

Product Service System in Circular Economy: A Bibliometric Analysis

As global attention to sustainable development increases, more and more works of literature emphasise the application of a circular economy-oriented product service system (PSS).The Circular economy aims to achieve economic and environmental sustainability through efficiency of resources and minimisation of waste. Meanwhile, product service systems are an emerging business model with the potential to facilitate product life extension and recycling. However,despite the growth of this field of study, there are relatively few bibliometric analyses of its application in the circular economy. Therefore, this study aims to use the method of bibliometrics,and with the help of VOS viewer visualisation software, to analyse the relevant literature the application of product-service systems under the guidance of circular economy in Scopus database from 2014 to 2023, and to discuss the publication types and trends, source distribution of publications, the most highly cited articles, and research hotspot keywords analysis. Thisstudyfound that keyword analysis identified four main topic clusters, in which significant hotspots focused on the Internet of Things, Industry 4.0, consumer behaviour, and reverse logistics.Therefore, this study may benefit researchers who wish to understand relevant academic results circular economy-oriented PSS applications.

Introduction of a carbon footprint assessment in the oil and gas facility life extension decision-making process

In large oil and gas producing countries, extraction and processing activities, including upstream activities, can represent a large share of domestic emissions. As oil fields approach their expected service life and reach depletion, energy use and GHG emissions increase per unit of produced oil, shifting operations away from their optimal point. Thus, it is paramount that oil field life extension decisions account for energy use and GHG emissions. However, many facilities are having their service life extended without considering this energy inefficiency and previous life extension decision making studies have neglected GHG emissions. Addressing this issue, this paper proposes the inclusion of a carbon footprint assessment within the evaluation of oil and gas offshore production facility life extension. The carbon footprint assessment adds an environmental lens to the evaluation of ageing, formerly evaluated according to material degradation, obsolescence and organizational issues. An eleven-stage framework is proposed to systematize the ageing related carbon footprint assessment and support life extension decision-making: (1) Objective definition, (2) Scope definition, (3) Field conditions description, (4) Scope breakdown into manageable portions, (5) Detailed data collection for each process and subsystem, (6) Input and output definition for each process and subsystem, (7) Process modelling, (8) Methodology definition for energy demand and inefficiency estimate, (9) Monitoring indicator definition, (10) Performance evaluation, and (11) Interpretation of results. The proposed framework is applied to a hypothetical case study, developed with data from a typical oil and gas offshore production platform operated in Brazil. Two LE improvement strategies were simulated, i.e. reducing the number of gas turbines, and increasing the export of natural gas. Both alter the modus operandi of the compression system and do not require additional equipment installation. These strategies resulted in a combined reduction of 922,000 tCO2 during the extended 10-year operation. This outcome demonstrates that by applying the framework opportunities for reducing energy use and GHG emissions during life extension can be identified and quantified, facilitating life extension decision-making.

Inhibition of a cyclic nucleotide-gated channel on neuronal cilia activates unfolded protein response in intestinal cells to promote longevity

Ciliary defects are linked to ciliopathies, but impairments in the sensory cilia of Caenorhabditis elegans neurons extend lifespan, a phenomenon with previously unclear mechanisms. Our study reveals that neuronal cilia defects trigger the unfolded protein response of the endoplasmic reticulum (UPR ER ) within intestinal cells, a process dependent on the insulin/insulin-like growth factor 1 (IGF-1) signaling transcription factor and the release of neuronal signaling molecules. While inhibiting UPR ER doesn’t alter the lifespan of wild-type worms, it normalizes the extended lifespan of ciliary mutants. Notably, deactivating the cyclic nucleotide-gated (CNG) channel TAX-4 on the ciliary membrane promotes lifespan extension through a UPR ER -dependent mechanism. Conversely, constitutive activation of TAX-4 attenuates intestinal UPR ER in ciliary mutants. Administering a CNG channel blocker to worm larvae activates intestinal UPR ER and increases adult longevity. These findings suggest that ciliary dysfunction in sensory neurons triggers intestinal UPR ER , contributing to lifespan extension and implying that transiently inhibiting ciliary channel activity may effectively prolong lifespan.

Preparation of Cellulose Fiber Loaded with CuO Nanoparticles for Enhanced Shelf Life and Quality of Tomato Fruit

The present study reports on the preparation of a cellulose fiber (CF) composite from D. lutescens, combined with copper oxide nanoparticles (DL@CF/CuO), to prolong the shelf life of tomatoes after harvest. The isolated cellulose fiber material was comprehensively characterized using XRD, FTIR, and FE-SEM analyses. The DLCF and DL@CF/CuO nanoparticles exhibited crystalline cellulose, as indicated by the XRD investigation. Both DLCF and DL@CF/CuO showed O-H and C-H FTIR spectra with identifiable vibrational peaks. The FE-SEM images depicted the dispersion of DL@CF/CuO-based fibers in a cellulose fiber matrix containing CuO nanoparticles. A 0.3% (wt/wt), a solution of DL@CF/CuO was coated onto the surface of early ripening tomato fruits. After a 25-day storage period at 25–29 °C and 85% RH, the results showed a significant extension in the shelf life of the tomato fruits, in line with changes in physiological properties and fruit quality. The extension of shelf life in tomato fruit epidermis treated with DL@CF/CuO was confirmed through FE-SEM analysis. L929 fibroblast cells were treated with the developed DL@CF/CuO nanocomposite, and no signs of toxicity were detected up to 75 µg/mL. Additionally, the DL@CF/CuO nanocomposite exhibited significant antifungal activity against Aspergillus flavus. In conclusion, this study provides novel insights for sustainable food security and waste control in the agricultural and food industries.

Regulatory Mechanisms of Aging Through the Nutritional and Metabolic Control of Amino Acid Signaling in Model Organisms

Life activities are supported by the intricate metabolic network that is fueled by nutrients. Nutritional and genetic studies in model organisms have determined that dietary restriction and certain mutations in the insulin signaling pathway lead to lifespan extension. Subsequently, the detailed mechanisms of aging as well as various nutrient signaling pathways and their relationships have been investigated in a wide range of organisms, from yeast to mammals. This review summarizes the roles of nutritional and metabolic signaling in aging and lifespan with a focus on amino acids, the building blocks of organisms. We discuss how lifespan is affected by the sensing, transduction, and metabolism of specific amino acids and consider the influences of life stage, sex, and genetic background on the nutritional control of aging. Our goal is to enhance our understanding of how nutrients affect aging and thus contribute to the biology of aging and lifespan.

Transcriptomic alterations in host parasitoid wasps resulting in extended lifespan due to PpNSRV-1 infection

The parasitoid wasp Pteromalus puparum, a pivotal agent in agricultural ecosystem balance, experiences significant alterations in lifespan due to infection by the negative-sense single-stranded RNA virus PpNSRV-1. This study utilized RNA sequencing (RNA-seq) to investigate the genetic mechanism(s) driving lifespan extension in response to this virus. Lifespan analysis, combined with RNA-seq of nearly isogenic lines of infected and uninfected wasps, yields a comprehensive temporal expression profile aligned with the P. puparum genome. Despite a modest overall impact of PpNSRV-1 on gene expression, notable effects were observed on specific gene families, such as the SPOP genes and the cytochrome P450 family. Through Weighted Gene Co-expression Network Analysis (WGCNA), we identified connections between the green and greenyellow modules to viral infection traits, with further functional analyses highlighting the pivotal roles of the Hedgehog, autophagy, AMPK, mTOR, p53, and PI3K-Akt signaling pathways. RNA interference experiment targeting the SPOP gene PPU06594-RA confirmed its role in lifespan modulation, underscoring the importance of Hedgehog pathway in the host’s adaptive response. These insights not only elucidate the complex genetic landscape of host-virus interactions but also open avenues for innovative biological pest control strategies.

Tribology in arthroplasty : Friction and wear, akey to along lifetime

This article is intended to highlight one of the key roles in endoprosthetic treatment with artificial implants and the extension of service life. Like every joint, artificial joints are subject to the physical laws of friction and wear-in short, tribology. Material pairings, surfaces and mechanisms of action in particular play adecisive role here. The special features and current findings relating to the three largest synovial joints (hip, knee and shoulder) will be discussed in detail and suggestions will be made for future developments. Continuous developments in the field of the tribology of artificial joints can massively improve care for patients. The revision figures and reasons already show the success of individual improvements in recent years.

From data to decision: integrated approach to pavement preservation in Iowa through treatment effectiveness analysis

ABSTRACT This investigation seeks to enhance ‘Iowa's Pavement Preservation Guide’ with a data-informed decision-making framework. Iowa DOT's databases were used as the data source for evaluating pavement performances under different preservation treatment regimens and determining the effectiveness of those strategies. Five preservation treatment methods for flexible and composite pavements, namely, crack sealing-and-filling, microsurfacing, slurry sealing, patching, and thin hot mix asphalt (HMA) overlays were evaluated using historic data from about 7000 road segments between 1998 and 2020. The data included various attributes describing pavement, road, and traffic characteristics required for analysing condition-based performance and treatment impacts. Two key indicators, service life extension (LE) and index benefit (IB), were defined and used to quantify treatment effectiveness in terms of pavement condition improvement and impact on deterioration rate. The treatment-effectiveness indicators were then factored into the cost analyses to assess the cost-effectiveness of preservation strategies. The results of the treatment effectiveness analysis were used to develop decision matrices that provide insights for selecting preservation treatments based on benefit–cost analysis considering both the overall condition and the dominant distress. This approach to treatment effectiveness highlighted the distinction between an optimum pavement preservation strategy and one that targets maximum service life extension.

Effects of Neem, Moringa, and Synthesized Silver Nanoparticles Coating on Postharvest Shelf Life and Quality Retention of Tomato (Solanum lycopersicum L.)

This study aimed to investigate the effects of synthesized silver nanoparticles (AgNPs), Azadirachta indica (neem), and Moringa oleifera (moringa) leaf extracts on the shelf life and quality retention of tomato (Solanum lycopersicum L.) fruits during storage. Thirty-five (35) red, matured tomato fruits were collected, rinsed and grouped for each treatment with AgNPs, neem and moringa coating: Control (n=5), moringa aqueous leaf extract (MALE) (n=5), neem aqueous leaf extract (NALE) (n=5), 1:9 and 6:4 moringa aqueous leaf extract synthesized silver nanoparticles (MALE-AgNPs) (n=5), 1:9 and 6:4 neem aqueous leaf extract synthesized silver nanoparticles (NALE-AgNPs) (n=5), respectively. The firmness, shelf life, and postharvest decay percentage of the tomato fruits were determined. Additionally, fungi associated with the postharvest deterioration of the fruits were isolated and identified using standard procedures. From the results of this study, tomato fruits coated with either neem or moringa crude extract showed the longest shelf life, as compared to the coating with AgNPs. Additionally, two fungi, namely Aspergillus niger and Aspergillus flavus, were isolated from the decayed tomato fruits. In conclusion, the neem and moringa leaf extracts are effective in the extension of the shelf life and retention of the quality of tomato fruits.

Trained immunity: A link between risk factors and cardiovascular disease.

Cardiovascular diseases are significant contributors to human mortality, closely associated with inflammation. With the changing living conditions and the extension of human lifespan, greater attention has been directed towards understanding the impact of early, long-term events on the development of cardiovascular events. Lifestyle factors such as stress, unhealthy diet and physical inactivity can increase the risk of cardiovascular diseases. Interestingly, even if the risk factors are addressed later, their influence may persist. Recently, the concept of trained innate immunity (TRIM), defined as sustained alterations in the function of innate immunocyte that promote a more robust response to downstream stimuli, has been proposed to be involved in cardiovascular diseases. It is hypothesized that TRIM may serve as a mediator bridging the impacts of aforementioned risk factors. This review aims to elucidate the role of TRIM in cardiovascular diseases and highlight its significance in uncovering new mechanisms and therapeutic targets.

Application of 3Rs in Caenorhabditis elegans Research for the Identification of Health-Promoting Natural Products.

The average age of the population is increasing worldwide, which has a profound impact on our society. This leads to an increasing demand for medicines and requires the development of new strategies to promote health during the additional years. In the search for resources and therapeutics for improved health during an extended life span, attention has to be paid to environmental exposure and ecosystem burdens that inevitably emerge with the extended consumption of medicines and drug development, even in the preclinical stage. The hereby introduced sustainable strategy for drug discovery is built on 3Rs, "R: obustness, R: eliability, and saving R: esources", inspired by both the 3Rs used in animal experiments and environmental protection, and centers on the usefulness and the variety of the small model organism Caenorhabditis elegans for detecting health-promoting natural products. A workflow encompassing a multilevel screening approach is presented to maximize the amount of information on health-promoting samples, while considering the 3Rs. A detailed, methodology- and praxis-oriented compilation and discussion of proposed C. elegans health span assays and more disease-specific assays are presented to offer guidance for scientists intending to work with C. elegans, thus facilitating the initial steps towards the integration of C. elegans assays in their laboratories.

Withholding or withdrawing life support in nephrology: a perspective in the French-speaking background

Chronic kidney disease (CKD) characterized by long duration, simplicity at beginning versus complexity at advanced stages. Hemodialysis and peritoneal dialysis are renal replacement therapy allowing life extension, but comorbidities and frailty could be burdensome over time. The academic society, Société Francophone de Néphrologie, Dialyse, Transplantation (SFNDT), publishes clinical practice guidelines to optimize CKD treatment in this context, to support shared decision-making in the appropriate initiation of and withdrawal from dialysis, and to supervise end-of-life cares in the French-speaking countries.

Unlocking the potential of chicken liver byproducts: Identification of antioxidant peptides through in silico approaches and anti-aging effects of a selected peptide in Caenorhabditis elegans

Chicken meat processing generates a substantial number of byproducts, which are either underutilized or improperly disposed. In this study, we employed in silico approaches to identify antioxidant peptides in chicken liver byproducts. Notably, the peptide WYR exhibited remarkable 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity with an IC50 of 0.13 ± 0.01 mg/mL and demonstrated stability under various conditions, including thermal, pH, NaCl, and simulated gastrointestinal digestion. Molecular docking analysis revealed significant hydrogen bonding interactions, while molecular dynamics showed differential stability with ABTS and 2,2-Diphenyl-1-picrylhydrazyl (DPPH). WYR exhibited improved stress resistance, decreased levels of reactive oxygen species (ROS), elevated the activities of superoxide dismutase (SOD) and catalase (CAT), and modulated the expression of crucial genes through the insulin/insulin-like growth factor (IIS) signaling pathway, mitogen-activated protein kinase (MAPK), and heat shock transcription factor-1 (HSF-1) pathways. These effects collectively contributed to the extension of Caenorhabditis elegans' lifespan. This study not only provides an effective method for antioxidant peptide analysis but also highlights the potential for enhancing the utilization of poultry byproducts.

Decelerating catalyst aging of natural gas engines using organic Rankine cycle under road conditions

High exhaust temperature is an intrinsic nature of natural gas engines which underlies power de-rating and thermal aging of after-treatment system; therefore, this study integrates an organic Rankine cycle (ORC) system between engine and it's three-way catalyst (TWC) to address these challenges. ORC facilitates power output enhancement through exhaust energy recovery and alleviates thermal aging by reducing exhaust temperature. To estimate the effectiveness of this hypothesized system, a simulation-based investigation is performed. First, simulation models, including engine, TWC, and vehicle dynamic models, are built and validated by experimental data. According to the temperature characteristics of different TWCs, three scenarios, representing old, current, and prospective TWC technology, are formulated to estimate the ORC performance under Worldwide Harmonized Light Vehicles Test Cycle. Results show that ORC system can substantially alleviate the thermal damage caused by high exhaust temperature and extend TWC lifespan. It is estimated that over 98.5 % of thermal damage can be decreased by proper ORC setting, and the average TWC lifespan extension can be at least 55.4, making a reduced noble metal usage and cost of TWC. Meanwhile, with the decrease of the working temperature of TWC, ORC can recover exhaust energy under more road conditions, further improving the net power and shortening the payback period of extra ORC hardware costs. A reduction in the working temperature of TWC from 770.5 K to 618 K yields a 109 % enhancement in maximum power, coupled with a 62.30 % reduction in the payback period. These findings fully reflect the advantage of ORC-TWC coupling and indicate that ORC is supposed to be used more for the TWC with a low working temperature to maximize economic effectiveness. This study provides a novel pathway for thermal aging alleviation of TWC and a valuable reference for prospective studies on matching ORC with TWC under road conditions.

Comparison of drug treatment intent in stage IV solid tumors in EU4+UK.

e23323 Background: The goal of cancer treatment may vary based on multiple factors. This study uses real-world data to compare treatment intent, and its evolution over time among patients with solid tumors; whilst we focus on stage IV cohorts, a comparison vs. stage I-III patients is also made, for context. Methods: Ipsos’ Global Oncology Monitor is a multi-stakeholder, physician-reported syndicated patient record database. 3,308 solid tumor-treating physicians (France = 834, Germany = 709, Italy = 578, Spain = 626, UK = 561) were screened for seniority and caseload and submitted data on 329,154 patients (France = 64,985, Germany = 77,709, Italy = 64,507, Spain = 65,427, UK = 56,526). Data were collected online from January 2020 to September 2023. Sample data were projected to the wider clinical population using market sizing extrapolations. Results: Of all solid tumor patients reported, regardless of stage, control cancer spread and/or growth (extend life) is the most common cited goal by sampled physicians when choosing drug therapy for the patient in question (average ~50% reported patients). This is followed by intent of eliminating cancer cells to undetectable levels (curative), while the intent to ease cancer symptoms (palliative) is typically less likely to be selected. Treatment intent at stage I-III showed similar trends, with curative being the most common goal (average ~70% of reported patients). When focusing on Stage IV solid tumors we observe life extension generally emerging as the main intention; a more nuanced analysis reveals similarity between Germany and Spain, where palliative intent is cited more often by sampled physicians compare to other regional counterparts. These differences are shown in Table 1. Little change seen in curative intent from 2020 to 2023 across all regions, except UK, where a downward trend is reflected from Q3 2022 onwards with a concurrent increase in extend life. Conclusions: This study indicates that treating to cure is a common aim for EU4+UK sampled physicians when giving drug therapy to stage I-III solid tumor patients, whilst extending life is the notable goal when considering stage IV patients. Additional analysis of tumor- and region-specific changes over time may help establish any potential influences on drug treatment choice due to factors such as reimbursement and treatment type availability. Further investigation using comparator cohort is warranted. [Table: see text]

Modulation of secondary metabolism and redox regulation by exogenously applied glutathione improves the shelf life of Capsicum annuum L. fruit

Role of redox homeostasis in fruit ripening of Capsicum annuum L. with oxidative metabolism was studied. The research aims the ability to reduce agents during postharvest storage on fruit for delayed ripening with the regulation of oxidative stress. Thus, we applied 10 mM reduced glutathione (GSH) to fruit as pretreatment followed by 1 mM hydrogen peroxide (H2O2) as ripening-inducing treatment and observed during 7 days of storage at 25 °C. A decrease in total soluble solid and firmness under H2O2, was increased while dehydration in tissue was decreased by GSH pretreatment. Glutathione regulated the turnover of organic acids to reducing sugars with higher activity of NADP malic enzyme that sustained the fruit coat photosynthesis through chlorophyll fluorescence, pigment composition, and photosystem II activity. Malondialdehyde accumulation was inversely correlated with GSH content and antioxidative enzyme activity that reduced loss of cell viability. Conclusively, regulation of oxidative stress with GSH may be effective in the extension of shelf life under postharvest storage.

Caloric restriction extends lifespan in a clonal plant.

When subjected to dietary caloric restriction (CR), individual animals often outlive well-fed conspecifics. Here, we address whether CR also extends lifespan in plants. Whereas caloric intake in animals comes from ingestion, in plants it derives from photosynthesis. Thus, factors that reduce photosynthesis, such as reduced light intensity, can induce CR. In two lab experiments investigating the aquatic macrophyte Lemna minor, we tracked hundreds of individuals longitudinally, with light intensity-and hence, CR-manipulated using neutral-density filters. In both experiments, CR dramatically increased lifespan through a process of temporal scaling. Moreover, the magnitude of lifespan extension accorded with the assumptions that (a) light intensity positively relates to photosynthesis following Michaelis-Menten kinetics, and (b) photosynthesis negatively relates to lifespan via a power law. Our results emphasize that CR-mediated lifespan extension applies to autotrophs as well as heterotrophs, and suggest that variation in light intensity has quantitatively predictable effects on plant aging trajectories.

Distinct mechanisms of non-autonomous UPRER mediated by GABAergic, glutamatergic, and octopaminergic neurons.

The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPRER) is one such conserved mechanism, which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPRER by overexpression of the major transcription factor, xbp-1s, solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissue to activate UPRER in a non-autonomous fashion. Previous work identified serotonergic and dopaminergic neurons in this signaling paradigm. To further expand our understanding of the neural circuitry that underlies the non-autonomous signaling of ER stress, we activated UPRER solely in glutamatergic, octopaminergic, and GABAergic neurons in C. elegans and paired whole-body transcriptomic analysis with functional assays. We found that UPRER-induced signals from glutamatergic neurons increased expression of canonical protein homeostasis pathways and octopaminergic neurons promoted pathogen response pathways, while minor, but statistically significant changes were observed in lipid metabolism-related genes with GABAergic UPRER activation. These findings provide further evidence for the distinct role neuronal subtypes play in driving the diverse response to ER stress.