scholarly journals Genetic basis of enhanced stress resistance in long-lived mutants highlights key role of innate immunity in determining longevity

2021 ◽  
Author(s):  
Sonja Soo ◽  
Paige Rudich ◽  
Meeta Mistry ◽  
Jeremy Van Raamsdonk
Keyword(s):  
Stress Response ◽  
Stress Resistance ◽  
Molecular Mechanisms ◽  
Bacterial Pathogen ◽  
Pathogen Resistance ◽  
Lifespan Extension ◽  
Sequencing Data ◽  
Enhanced Resistance ◽  
Resistance To Stress ◽  
Highly Correlated

Mutations that extend lifespan are associated with enhanced resistance to stress. To better understand the molecular mechanisms underlying this relationship, we studied nine long-lived C. elegans mutants representative of different pathways of lifespan extension. We directly compared the magnitude of their lifespan extension and their ability to resist various external stressors (heat, oxidative stress, bacterial pathogens, osmotic stress, and anoxia). Furthermore, we analysed gene expression in each of these mutants to identify genes and pathways responsible for the enhanced resistance to stress. All of the examined long-lived mutants have increased resistance to one or more type of stress. Resistance to each of the examined types of stress had a significant, positive correlation with lifespan, with bacterial pathogen resistance showing the strongest relationship. All of the examined long-lived mutants have significant upregulation of multiple stress response pathways but differ in which stress response pathway has the greatest enrichment of genes. We used RNA sequencing data to identify which genes are most highly correlated with each type of stress resistance. There was a highly significant overlap between genes highly correlated with stress resistance, and genes highly correlated with longevity, suggesting that the same genetic pathways drive both phenotypes. This was especially true for genes correlated with bacterial pathogen resistance, which showed an 84% overlap with genes correlated with lifespan. Overall, our results demonstrate a strong correlation between stress resistance and longevity that results from the high degree of overlap in genes contributing to each phenotype.

The potential of new genetic technologies in selecting for stress resistance in pigs

2005 ◽  
Vol 45 (8) ◽  
pp. 775
Author(s):  
C. A. Kerr ◽  
B. M. Hines
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Stress Resistance ◽  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Negative Impact ◽  
Experimental Models ◽  
Genetic Technologies ◽  
On Farm ◽  
Commercial Environment

This paper examines the potential for breeding stress resistance in pigs through an understanding of the physiology of the stress response and its associated genetic basis. Pigs reared in commercial units can encounter numerous concurrent stressors that can have a negative impact on performance and welfare. Stress induces physiological and behavioural responses that are multidimensional, consisting of a complex neuroendocrine and immune signalling milieu. Some stress-related genetic parameters have been identified using conventional genetic approaches applied in experimental models. However, these traits do not capture the complexity of the stress response. As a result, the molecular mechanisms underlying the variation associated with stress resistance in pigs in a commercial environment is poorly understood. Gene expression profiling is a powerful tool that can be applied to systematically elucidate stress response pathways and networks. Consequently, gene expression technologies have been applied to identify some putative stress-regulated genes. Further application of these and more traditional technologies will aid in elucidating stress resistance using gene expression as a measure of phenotypic variation at a molecular level. It is envisaged that in the future, tools for selecting for stress resistance could eventually be applied on-farm to enhance production, health and welfare status.

scholarly journals Sex enhances survival in Paramecium

2019 ◽  
Author(s):  
Amarinder Singh Thind ◽  
Valerio Vitali ◽  
Mario R. Guarracino ◽  
Francesco Catania
Keyword(s):  
Genetic Variation ◽  
Stress Response ◽  
Sexual Reproduction ◽  
Stress Resistance ◽  
Evolutionary Biology ◽  
Molecular Mechanisms ◽  
Adaptive Significance ◽  
Paramecium Tetraurelia ◽  
Self Fertilization

AbstractThe pervasiveness of sex despite its well-known costs is a long-standing puzzle in evolutionary biology. Current explanations for the success of sex in nature largely rely on the adaptive significance of the new or rare genotypes that sex may generate. Less explored is the possibility that sex-underlying molecular mechanisms can enhance fitness and convey benefits to the individuals that bear the immediate costs of sex. Here we show that self-fertilization can increase stress resistance in the ciliate Paramecium tetraurelia. This advantage is independent of new genetic variation, coupled with a reduced nutritional input, and offers fresh insights into the mechanistic origin of sex. In addition to providing evidence that the molecular underpinnings of sexual reproduction and the stress response are linked in P. tetraurelia, these findings supply an explanation for the persistence of self-fertilization in this ciliate.

scholarly journals What’s Genetic Variation Got to Do with It? Starvation-Induced Self-Fertilization Enhances Survival in Paramecium

2020 ◽  
Vol 12 (5) ◽  
pp. 626-638 ◽  
Author(s):  
Amarinder Singh Thind ◽  
Valerio Vitali ◽  
Mario Rosario Guarracino ◽  
Francesco Catania
Keyword(s):  
Genetic Variation ◽  
Stress Response ◽  
Sexual Reproduction ◽  
Stress Resistance ◽  
Evolutionary Biology ◽  
Molecular Mechanisms ◽  
Adaptive Significance ◽  
Paramecium Tetraurelia ◽  
Self Fertilization

Abstract The pervasiveness of sex despite its well-known costs is a long-standing puzzle in evolutionary biology. Current explanations for the success of sex in nature largely rely on the adaptive significance of the new or rare genotypes that sex may generate. Less explored is the possibility that sex-underlying molecular mechanisms can enhance fitness and convey benefits to the individuals that bear the immediate costs of sex. Here, we show that the molecular environment associated with self-fertilization can increase stress resistance in the ciliate Paramecium tetraurelia. This advantage is independent of new genetic variation, coupled with a reduced nutritional input, and offers fresh insights into the mechanistic origin of sex. In addition to providing evidence that the molecular underpinnings of sexual reproduction and the stress response are linked in P. tetraurelia, these findings supply an integrative explanation for the persistence of self-fertilization in this ciliate.

Growth phase dependent resistance to oxidative stress in a phytopathogen Xanthomonas oryzae pv. oryzae

1995 ◽  
Vol 41 (11) ◽  
pp. 1043-1047 ◽  
Author(s):  
Paiboon Vattanaviboon ◽  
Wipa Praituan ◽  
Skorn Mongkolsuk
Keyword(s):  
Oxidative Stress ◽  
Stationary Phase ◽  
Growth Phase ◽  
Stress Resistance ◽  
De Novo ◽  
Bacterial Pathogen ◽  
Stationary Growth Phase ◽  
Xanthomonas Oryzae ◽  
Resistance To Stress ◽  
De Novo Protein Synthesis

Xanthomonas oryzae pv. oryzae, a rice bacterial pathogen, showed growth phase dependent resistance to oxidative stress killing. Stationary phase cells were much more resistant to killing concentrations of H2O2, organic peroxides, and a superoxide generator (menadione) than cells from early log and mid-log phases. The stationary phase stress resistance phenotype did not require de novo protein synthesis. Also, nutrient starvation or media metabolites were not inducing signals for the phenotype. The stationary phase stress resistance did not apply to all types of stress. For example, X. oryzae pv. oryzae was equally sensitive to heat and pH 5.5 stress at all growth phases tested. This pattern of stationary phase resistance to stress differs from observations in other bacteria and could be important in plant–microbe interactions.Key words: phytopathogen, stationary growth phase, resistance to oxidative stress killing.

scholarly journals ATF-4 and hydrogen sulfide signalling mediate longevity from inhibition of translation or mTORC1

2020 ◽  
Author(s):  
Cyril Statzer ◽  
Richard Venz ◽  
Monet Bland ◽  
Stacey Robida-Stubbs ◽  
Jin Meng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
Hydrogen Sulfide ◽  
Stress Response ◽  
Stress Resistance ◽  
Lifespan Extension ◽  
C Elegans ◽  
Mechanistic Target Of Rapamycin ◽  
Therapeutic Benefits ◽  
Transcription Program

AbstractInhibition of mTORC1 (mechanistic target of rapamycin 1) slows ageing, but mTORC1 supports fundamental processes that include protein synthesis, making it critical to elucidate how mTORC1 inhibition increases lifespan. Under stress conditions, the integrated stress response (ISR) globally suppresses protein synthesis, resulting in preferential translation of the transcription factor ATF-4. Here we show in C. elegans that the ATF-4 transcription program promotes longevity and that ATF-4 upregulation mediates lifespan extension from mTORC1 inhibition. ATF-4 activates canonical anti-ageing mechanisms but also increases expression of transsulfuration enzymes to promote hydrogen sulfide (H2S) production. ATF-4-induced H2S production mediates longevity and stress resistance from C. elegans mTORC1 suppression, and ATF4 drives H2S production in mammalian dietary restriction. This H2S boost increases protein persulfidation, a protective modification of redox-reactive cysteines. Increasing H2S levels, or enhancing mechanisms that H2S modulates through persulfidation, may represent promising strategies for mobilising therapeutic benefits of the ISR or mTORC1 inhibition.

scholarly journals In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Expression Profiles ◽  
Cell Types ◽  
Sequencing Data ◽  
Disease Stages ◽  
Post Transcriptional Regulation

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

scholarly journals Overexpression of the Apple (Malus× domestica) MdERF100 in Arabidopsis Increases Resistance to Powdery Mildew

2021 ◽  
Vol 22 (11) ◽  
pp. 5713
Author(s):  
Yiping Zhang ◽  
Li Zhang ◽  
Hai Ma ◽  
Yichu Zhang ◽  
Xiuming Zhang ◽  
...  
Keyword(s):  
Stress Response ◽  
Powdery Mildew ◽  
Malus Domestica ◽  
Molecular Mechanisms ◽  
Powdery Mildew Resistance ◽  
Bimolecular Fluorescence Complementation ◽  
Bhlh Protein ◽  
Mildew Resistance ◽  
Sa Signaling

APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) transcription factors play important roles in plant development and stress response. Although AP2/ERF genes have been extensively investigated in model plants such as Arabidopsis thaliana, little is known about their role in biotic stress response in perennial fruit tree crops such as apple (Malus × domestica). Here, we investigated the role of MdERF100 in powdery mildew resistance in apple. MdERF100 localized to the nucleus but showed no transcriptional activation activity. The heterologous expression of MdERF100 in Arabidopsis not only enhanced powdery mildew resistance but also increased reactive oxygen species (ROS) accumulation and cell death. Furthermore, MdERF100-overexpressing Arabidopsis plants exhibited differential expressions of genes involved in jasmonic acid (JA) and salicylic acid (SA) signaling when infected with the powdery mildew pathogen. Additionally, yeast two-hybrid and bimolecular fluorescence complementation assays confirmed that MdERF100 physically interacts with the basic helix–loop–helix (bHLH) protein MdbHLH92. These results suggest that MdERF100 mediates powdery mildew resistance by regulating the JA and SA signaling pathways, and MdbHLH92 is involved in plant defense against powdery mildew. Overall, this study enhances our understanding of the role of MdERF genes in disease resistance, and provides novel insights into the molecular mechanisms of powdery mildew resistance in apple.

scholarly journals Identification of Biomolecules Involved in the Adaptation to the Environment of Cold-Loving Microorganisms and Metabolic Pathways for Their Production

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1155
Author(s):  
Eva Garcia-Lopez ◽  
Paula Alcazar ◽  
Cristina Cid
Keyword(s):  
Metabolic Pathways ◽  
Extracellular Polymeric Substances ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Analytical Techniques ◽  
Light Protection ◽  
Domains Of Life ◽  
Mechanisms Of Adaptation ◽  
Resistance To Stress ◽  
Function Discovery

Cold-loving microorganisms of all three domains of life have unique and special abilities that allow them to live in harsh environments. They have acquired structural and molecular mechanisms of adaptation to the cold that include the production of anti-freeze proteins, carbohydrate-based extracellular polymeric substances and lipids which serve as cryo- and osmoprotectants by maintaining the fluidity of their membranes. They also produce a wide diversity of pigmented molecules to obtain energy, carry out photosynthesis, increase their resistance to stress and provide them with ultraviolet light protection. Recently developed analytical techniques have been applied as high-throughoutput technologies for function discovery and for reconstructing functional networks in psychrophiles. Among them, omics deserve special mention, such as genomics, transcriptomics, proteomics, glycomics, lipidomics and metabolomics. These techniques have allowed the identification of microorganisms and the study of their biogeochemical activities. They have also made it possible to infer their metabolic capacities and identify the biomolecules that are parts of their structures or that they secrete into the environment, which can be useful in various fields of biotechnology. This Review summarizes current knowledge on psychrophiles as sources of biomolecules and the metabolic pathways for their production. New strategies and next-generation approaches are needed to increase the chances of discovering new biomolecules.

scholarly journals VTC4 Polyphosphate Polymerase Knockout Increases Stress Resistance of Saccharomyces cerevisiae Cells

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 487
Author(s):  
Alexander Tomashevsky ◽  
Ekaterina Kulakovskaya ◽  
Ludmila Trilisenko ◽  
Ivan V. Kulakovskiy ◽  
Tatiana Kulakovskaya ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Heavy Metal ◽  
Stress Response ◽  
Stress Resistance ◽  
Alkaline Stress ◽  
Inorganic Polyphosphate ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Elevated Expression ◽  
Chaperone Complex

Inorganic polyphosphate (polyP) is an important factor of alkaline, heavy metal, and oxidative stress resistance in microbial cells. In yeast, polyP is synthesized by Vtc4, a subunit of the vacuole transporter chaperone complex. Here, we report reduced but reliably detectable amounts of acid-soluble and acid-insoluble polyPs in the Δvtc4 strain of Saccharomyces cerevisiae, reaching 10% and 20% of the respective levels of the wild-type strain. The Δvtc4 strain has decreased resistance to alkaline stress but, unexpectedly, increased resistance to oxidation and heavy metal excess. We suggest that increased resistance is achieved through elevated expression of DDR2, which is implicated in stress response, and reduced expression of PHO84 encoding a phosphate and divalent metal transporter. The decreased Mg2+-dependent phosphate accumulation in Δvtc4 cells is consistent with reduced expression of PHO84. We discuss a possible role that polyP level plays in cellular signaling of stress response mobilization in yeast.

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