Western diet-induced cognitive and metabolic dysfunctions in aged mice are prevented by rosmarinic acid in a sex-dependent fashion.

Background & Aims: Unhealthy lifestyles, such as chronic consumption of a Western Diet (WD), have been associated with increased systemic inflammation and oxidative stress (OS), a condition that may favour cognitive dysfunctions during aging. Polyphenols, such as rosmarinic acid (RA) may buffer low-grade inflammation and OS, characterizing the aging brain that is sustained by WD, promoting healthspan. The aim of this study was to evaluate the ability of RA to prevent cognitive decline in a mouse model of WD-driven unhealthy aging and to gain knowledge on the specific molecular pathways modulated within the brain.

A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging.

To ameliorate or even prevent signatures of aging in ultimately humans, we here report the identification of a previously undescribed polyacetylene contained in the root of carrots (Daucus carota), hereafter named isofalcarintriol, which we reveal as potent promoter of longevity in the nematode C. elegans. We assign the absolute configuration of the compound as (3 S,8 R,9 R,E)-heptadeca-10-en-4,6-diyne-3,8,9-triol, and develop a modular asymmetric synthesis route for all E-isofalcarintriol stereoisomers.

Rosmarinic Acid Improves Cognitive Abilities and Glucose Metabolism in Aged C57Bl/6N Mice While Disrupting Lipid Profile in Young Adults in a Sex-Dependent Fashion.

A growing body of evidence suggests that regular consumption of natural products might promote healthy aging; however, their mechanisms of action are still unclear. Rosmarinic acid (RA) is a polyphenol holding anti-inflammatory, antioxidant and neuroprotective properties. The aim of this study was to characterise the efficacy of an oral administration of RA in promoting healthspan in a mouse model of physiological aging.

Type 2 Diabetes risk alleles in Peptidyl-glycine Alpha-amidating Monooxygenase influence GLP-1 levels and response to GLP-1 Receptor Agonists.

Patients with type 2 diabetes vary in their response to currently available therapeutic agents (including GLP-1 receptor agonists) leading to suboptimal glycemic control and increased risk of complications. We show that human carriers of hypomorphic T2D-risk alleles in the gene encoding peptidyl-glycine alpha-amidating monooxygenase as well as -knockout mice, display increased resistance to GLP-1 . inactivation in mice leads to reduced gastric GLP-1R expression and faster gastric emptying: this persists during GLP-1R agonist treatment and is rescued when GLP-1R activity is antagonized, indicating resistance to GLP-1's gastric slowing properties.

Lithium treatment extends human lifespan: findings from the UK Biobank.

Lithium is a nutritional trace element that is also used pharmacologically for the management of bipolar and related psychiatric disorders. Recent studies have shown that lithium supplementation can extend health and lifespan in different animal models. Moreover, nutritional lithium uptake from drinking water was repeatedly found to be positively correlated with human longevity.

The sex-specific metabolic signature of C57BL/6NRj mice during aging.

Due to intact reactive oxygen species homeostasis and glucose metabolism, C57BL/6NRj mice are especially suitable to study cellular alterations in metabolism. We applied Nuclear Magnetic resonance spectroscopy to analyze five different tissues of this mouse strain during aging and included female and male mice aged 3, 6, 12, and 24 months. Metabolite signatures allowed separation between the age groups in all tissues, and we identified the most prominently changing metabolites in female and male tissues.

Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs.

Age-associated diseases represent a growing burden for global health systems in our aging society. Consequently, we urgently need innovative strategies to counteract these pathological disturbances. Overwhelming generation of reactive oxygen species (ROS) is associated with age-related damage, leading to cellular dysfunction and, ultimately, diseases.

Ingestion of single guide RNAs induces gene overexpression and extends lifespan in Caenorhabditis elegans via CRISPR activation.

Inhibition of gene expression in Caenorhabditis elegans, a versatile model organism for studying the genetics of development and aging, is achievable by feeding nematodes with bacteria expressing specific dsRNAs. Overexpression of hypoxia-inducible factor 1 (hif-1) or heat-shock factor 1 (hsf-1) by conventional transgenesis has previously been shown to promote nematodal longevity. However, it is unclear whether other methods of gene overexpression are feasible, particularly with the advent of CRISPR-based techniques.

Evolutionarily conserved transcription factors as regulators of longevity and targets for geroprotection.

Aging is the single largest risk factor for many debilitating conditions, including heart diseases, stroke, cancer, diabetes, and neurodegenerative disorders. Although far from understood in its full complexity, it is scientifically well established that aging is influenced by genetic and environmental factors and can be modulated by various interventions. One of aging's early hallmarks is aberrations in transcriptional networks, controlling for example metabolic homeostasis or the response to stress.

Pollinator guilds respond contrastingly at different scales to landscape parameters of land-use intensity.

Land-use intensification is the main factor for the catastrophic decline of insect pollinators. However, land-use intensification includes multiple processes that act across various scales and should affect pollinator guilds differently depending on their ecology. We aimed to reveal how two main pollinator guilds, wild bees and hoverflies, respond to different land-use intensification measures, that is, arable field cover (AFC), landscape heterogeneity (LH), and functional flower composition of local plant communities as a measure of habitat quality.

Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan.

Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans.

Green tea catechins EGCG and ECG enhance the fitness and lifespan of by complex I inhibition.

Green tea catechins are associated with a delay in aging. We have designed the current study to investigate the impact and to unveil the target of the most abundant green tea catechins, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG). Experiments were performed in to analyze cellular metabolism, ROS homeostasis, stress resistance, physical exercise capacity, health- and lifespan, and the underlying signaling pathways.

Interrelation between ROS and Ca in aging and age-related diseases.

Calcium (Ca) and reactive oxygen species (ROS) are versatile signaling molecules coordinating physiological and pathophysiological processes. While channels and pumps shuttle Ca ions between extracellular space, cytosol and cellular compartments, short-lived and highly reactive ROS are constantly generated by various production sites within the cell. Ca controls membrane potential, modulates mitochondrial adenosine triphosphate (ATP) production and affects proteins like calcineurin (CaN) or calmodulin (CaM), which, in turn, have a wide area of action.

Author Correction: Partial impairment of insulin receptor expression mimics fasting to prevent diet-induced fatty liver disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Partial impairment of insulin receptor expression mimics fasting to prevent diet-induced fatty liver disease.

Excessive insulin signaling through the insulin receptor (IR) may play a role in the pathogenesis of diet-induced metabolic disease, including obesity and type 2 diabetes. Here we investigate whether heterozygous impairment of insulin receptor (IR) expression limited to peripheral, i.e.

Endogenous metabolites promote stress resistance through induction of mitohormesis.

Interventions and small molecules, which promote formation of reactive oxygen species (ROS), have repeatedly been shown to increase stress resistance and lifespan of different model organisms. These phenotypes occur only in response to low concentrations of ROS, while higher concentrations exert opposing effects. This non-linear or hormetic dose-response relationship has been termed mitohormesis, since ROS are mainly generated within the mitochondrial compartment.

Redox-mediated regulation of aging and healthspan by an evolutionarily conserved transcription factor HLH-2/Tcf3/E2A.

Physiological aging is a complex process, influenced by a plethora of genetic and environmental factors. While being far from fully understood, a number of common aging hallmarks have been elucidated in recent years. Among these, transcriptomic alterations are hypothesized to represent a crucial early manifestation of aging.

Deficiency in ROS-sensing nuclear factor erythroid 2-like 2 causes altered glucose and lipid homeostasis following exercise training.

Oxidative stress induced by acute exercise may regulate exercise training-induced adaptations that improve metabolic health. One of the central transcription regulatory targets of reactive oxygen species (ROS) is Nrf2 (nuclear factor erythroid-derived 2-like 2, or NFE2L2). Here, we investigated whether global deficiency of Nrf2 in mice would impact exercise training-induced changes in glucose and lipid homeostasis.

Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan.

Mitochondrial complex I-the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery-has been proposed to contribute to a variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear (nDNA) and mitochondrial DNA (mtDNA). While some association studies of mtDNA encoded complex I genes and lifespan in humans have been reported, experimental evidence and the functional consequence of such variants is limited to studies using invertebrate models.

Publisher Correction: Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.

The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a blue stripe in place of a red stripe at the right-hand end of the scale.

Aging and drug discovery.

Multiple interventions in the aging process have been discovered to extend the healthspan of model organisms. Both industry and academia are therefore exploring possible transformative molecules that target aging and age-associated diseases. In this overview, we summarize the presented talks and discussion points of the 5th Annual Aging and Drug Discovery Forum 2018 in Basel, Switzerland.