Longevity extension by phytochemicals.

PubMed

Leonov, Anna; Arlia-Ciommo, Anthony; Piano, Amanda; Svistkova, Veronika; Lutchman, Vicky; Medkour, Younes; Titorenko, Vladimir I

2015-04-13

Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract natural predators of such organisms, as well as lure pollinators and other symbiotes of these plants. In addition, many phytochemicals can extend longevity in heterotrophic organisms across phyla via evolutionarily conserved mechanisms. In this review, we discuss such mechanisms. We outline how structurally diverse phytochemicals modulate a complex network of signaling pathways that orchestrate a distinct set of longevity-defining cellular processes. This review also reflects on how the release of phytochemicals by plants into a natural ecosystem may create selective forces that drive the evolution of longevity regulation mechanisms in heterotrophic organisms inhabiting this ecosystem. We outline the most important unanswered questions and directions for future research in this vibrant and rapidly evolving field.

Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking.

PubMed

Orozco, Helena; Matallana, Emilia; Aranda, Agustín

2013-01-02

Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it. Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS. Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins) and posttranscriptional (i.e., mRNA binding protein Pub1) levels allows to modulate yeast life span during its biotechnological use. Due to links between aging and metabolism, it also influences the

Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: Mitochondria as a "chi".

PubMed

Cornelius, Carolin; Perrotta, Rosario; Graziano, Antonio; Calabrese, Edward J; Calabrese, Vittorio

2013-04-25

Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways. By sensing the intracellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by coordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose-response, challenges long-standing beliefs about the nature of the dose-response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced

Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans

PubMed Central

Hwang, Ara B.; Ryu, Eun-A; Artan, Murat; Chang, Hsin-Wen; Kabir, Mohammad Humayun; Nam, Hyun-Jun; Lee, Dongyeop; Yang, Jae-Seong; Kim, Sanguk; Mair, William B.; Lee, Cheolju; Lee, Siu Sylvia; Lee, Seung-Jae

2014-01-01

Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS. PMID:25288734

Longevity and its regulation: centenarians and beyond.

PubMed

Robert, L; Fulop, T

2014-01-01

Regulation of longevity depends on genetic and environmental factors. According to Svanborg, a Swedish geriatrician, over the last decades human life expectancy increased as well as the age at onset of fatal diseases. Nevertheless, autopsies of centenarians revealed the presence of several severe pathologies which could have killed them much earlier. Therefore, the emphasis is on regulation of resistance dependent on the expression of genes such as Sirtuins, mTOR pathway and others controlling body resistance. Only a small fraction (<1%) of centenarians live to become supercentenarians (110 years), indicating a limit of performance and resistance of the body. This limit can be interpreted as 'tinkering' of nature instead of producing masterpieces as suggested by F. Jacob. These facts and theories are described in this chapter.

Comparative Endocrinology of Aging and Longevity Regulation

PubMed Central

Allard, John B.; Duan, Cunming

2011-01-01

Hormones regulate growth, development, metabolism, and other complex processes in multicellular animals. For many years it has been suggested that hormones may also influence the rate of the aging process. Aging is a multifactorial process that causes biological systems to break down and cease to function in adult organisms as time passes, eventually leading to death. The exact underlying causes of the aging process remain a topic for debate, and clues that may shed light on these causes are eagerly sought after. In the last two decades, gene mutations that result in delayed aging and extended longevity have been discovered, and many of the affected genes have been components of endocrine signaling pathways. In this review we summarize the current knowledge on the roles of endocrine signaling in the regulation of aging and longevity in various animals. We begin by discussing the notion that conserved systems, including endocrine signaling pathways, “regulate” the aging process. Findings from the major model organisms: worms, flies, and rodents, are then outlined. Unique lessons from studies of non-traditional models: bees, salmon, and naked mole rats, are also discussed. Finally, we summarize the endocrinology of aging in humans, including changes in hormone levels with age, and the involvement of hormones in aging-related diseases. The most well studied and widely conserved endocrine pathway that affects aging is the insulin/insulin-like growth factor system. Mutations in genes of this pathway increase the lifespan of worms, flies, and mice. Population genetic evidence also suggests this pathway’s involvement in human aging. Other hormones including steroids have been linked to aging only in a subset of the models studied. Because of the value of comparative studies, it is suggested that the aging field could benefit from adoption of additional model organisms. PMID:22654825

Broad spectrum detoxification: the major longevity assurance process regulated by insulin/IGF-1 signaling?

PubMed

Gems, David; McElwee, Joshua J

2005-03-01

Our recent survey of genes regulated by insulin/IGF-1 signaling (IIS) in Caenorhabditis elegans suggests a role for a number of gene classes in longevity assurance. Based on these findings, we propose a model for the biochemistry of longevity assurance and ageing, which is as follows. Ageing results from molecular damage from highly diverse endobiotic toxins. These are stochastic by-products of diverse metabolic processes, of which reactive oxygen species (ROS) are likely to be only one component. Our microarray analysis suggests a major role in longevity assurance of the phase 1, phase 2 detoxification system involving cytochrome P450 (CYP), short-chain dehydrogenase/reductase (SDR) and UDP-glucuronosyltransferase (UGT) enzymes. Unlike superoxide and hydrogen peroxide detoxification, this system is energetically costly, and requires the excretion from the cell of its products. Given such costs, its activity may be selected against, as predicted by the disposable soma theory. CYP and UGT enzymes target lipophilic molecular species; insufficient activity of this system is consistent with age-pigment (lipofuscin) accumulation during ageing. We suggest that IIS-regulated longevity assurance involves: (a) energetically costly detoxification and excretion of molecular rubbish, and (b) conservation of existing proteins via molecular chaperones. Given the emphasis in this theory on investment in cellular waste disposal, and on protein conservation, we have dubbed it the green theory.

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

PubMed

De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

Stress responses during ageing: molecular pathways regulating protein homeostasis.

PubMed

Kyriakakis, Emmanouil; Princz, Andrea; Tavernarakis, Nektarios

2015-01-01

The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.

Longevity and Stress Resistant Property of 6-Gingerol from Zingiber officinale Roscoe in Caenorhabditis elegans.

PubMed

Lee, Eun Byeol; Kim, Jun Hyeong; An, Chang Wan; Kim, Yeong Jee; Noh, Yun Jeong; Kim, Su Jin; Kim, Ju-Eun; Shrestha, Abinash Chandra; Ham, Ha-Neul; Leem, Jae-Yoon; Jo, Hyung-Kwon; Kim, Dae-Sung; Moon, Kwang Hyun; Lee, Jeong Ho; Jeong, Kyung Ok; Kim, Dae Keun

2018-03-14

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans ( C. elegans ) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans , and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

Salicylic acid 3-hydroxylase regulates Arabidopsis leaf longevity by mediating salicylic acid catabolism

PubMed Central

Zhang, Kewei; Halitschke, Rayko; Yin, Changxi; Liu, Chang-Jun; Gan, Su-Sheng

2013-01-01

The plant hormone salicylic acid (SA) plays critical roles in plant defense, stress responses, and senescence. Although SA biosynthesis is well understood, the pathways by which SA is catabolized remain elusive. Here we report the identification and characterization of an SA 3-hydroxylase (S3H) involved in SA catabolism during leaf senescence. S3H is associated with senescence and is inducible by SA and is thus a key part of a negative feedback regulation system of SA levels during senescence. The enzyme converts SA (with a Km of 58.29 µM) to both 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-DHBA in vitro but only 2,3-DHBA in vivo. The s3h knockout mutants fail to produce 2,3-DHBA sugar conjugates, accumulate very high levels of SA and its sugar conjugates, and exhibit a precocious senescence phenotype. Conversely, the gain-of-function lines contain high levels of 2,3-DHBA sugar conjugates and extremely low levels of SA and its sugar conjugates and display a significantly extended leaf longevity. This research reveals an elegant SA catabolic mechanism by which plants regulate SA levels by converting it to 2,3-DHBA to prevent SA overaccumulation. The research also provides strong molecular genetic evidence for an important role of SA in regulating the onset and rate of leaf senescence. PMID:23959884

Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

PubMed

Epel, Elissa S; Lithgow, Gordon J

2014-06-01

The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The microRNA machinery regulates fasting-induced changes in gene expression and longevity in Caenorhabditis elegans.

PubMed

Kogure, Akiko; Uno, Masaharu; Ikeda, Takako; Nishida, Eisuke

2017-07-07

Intermittent fasting (IF) is a dietary restriction regimen that extends the lifespans of Caenorhabditis elegans and mammals by inducing changes in gene expression. However, how IF induces these changes and promotes longevity remains unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs), small non-coding RNAs (∼22 nucleotides) that repress gene expression and whose expression can be altered by fasting. To test this proposition, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans We revealed that fasting up-regulated the expression of the miRNA-induced silencing complex (miRISC) components, including Argonaute and GW182, and the miRNA-processing enzyme DRSH-1 (the ortholog of the Drosophila Drosha enzyme). Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knock-out or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector in C. elegans Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1 , a gene encoding GW182, respectively. Moreover, miRNA array analyses revealed that the expression levels of numerous miRNAs changed after 2 days of fasting. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme DRSH-1, play an important role in mediating IF-induced longevity via the regulation of fasting-induced changes in gene expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

An Energy-Independent Pro-longevity Function of Triacylglycerol in Yeast

PubMed Central

Hall, Kevin W.; Deng, Xiexiong; Li, Pan; Benning, Christoph; Williams, Barry L.; Kuo, Min-Hao

2016-01-01

Intracellular triacylglycerol (TAG) is a ubiquitous energy storage lipid also involved in lipid homeostasis and signaling. Comparatively, little is known about TAG’s role in other cellular functions. Here we show a pro-longevity function of TAG in the budding yeast Saccharomyces cerevisiae. In yeast strains derived from natural and laboratory environments a correlation between high levels of TAG and longer chronological lifespan was observed. Increased TAG abundance through the deletion of TAG lipases prolonged chronological lifespan of laboratory strains, while diminishing TAG biosynthesis shortened lifespan without apparently affecting vegetative growth. TAG-mediated lifespan extension was independent of several other known stress response factors involved in chronological aging. Because both lifespan regulation and TAG metabolism are conserved, this cellular pro-longevity function of TAG may extend to other organisms. PMID:26907989

The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

PubMed

Oliver, Shüné V; Brooke, Basil D

2016-01-01

Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance

Genetic Analysis Reveals a Longevity-Associated Protein Modulating Endothelial Function and Angiogenesis.

PubMed

Villa, Francesco; Carrizzo, Albino; Spinelli, Chiara C; Ferrario, Anna; Malovini, Alberto; Maciąg, Anna; Damato, Antonio; Auricchio, Alberto; Spinetti, Gaia; Sangalli, Elena; Dang, Zexu; Madonna, Michele; Ambrosio, Mariateresa; Sitia, Leopoldo; Bigini, Paolo; Calì, Gaetano; Schreiber, Stefan; Perls, Thomas; Fucile, Sergio; Mulas, Francesca; Nebel, Almut; Bellazzi, Riccardo; Madeddu, Paolo; Vecchione, Carmine; Puca, Annibale A

2015-07-31

Long living individuals show delay of aging, which is characterized by the progressive loss of cardiovascular homeostasis, along with reduced endothelial nitric oxide synthase activity, endothelial dysfunction, and impairment of tissue repair after ischemic injury. Exploit genetic analysis of long living individuals to reveal master molecular regulators of physiological aging and new targets for treatment of cardiovascular disease. We show that the polymorphic variant rs2070325 (Ile229Val) in bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) associates with exceptional longevity, under a recessive genetic model, in 3 independent populations. Moreover, the expression of BPIFB4 is instrumental to maintenance of cellular and vascular homeostasis through regulation of protein synthesis. BPIFB4 phosphorylation/activation by protein-kinase-R-like endoplasmic reticulum kinase induces its complexing with 14-3-3 and heat shock protein 90, which is facilitated by the longevity-associated variant. In isolated vessels, BPIFB4 is upregulated by mechanical stress, and its knock-down inhibits endothelium-dependent vasorelaxation. In hypertensive rats and old mice, gene transfer of longevity-associated variant-BPIFB4 restores endothelial nitric oxide synthase signaling, rescues endothelial dysfunction, and reduces blood pressure levels. Furthermore, BPIFB4 is implicated in vascular repair. BPIFB4 is abundantly expressed in circulating CD34(+) cells of long living individuals, and its knock-down in endothelial progenitor cells precludes their capacity to migrate toward the chemoattractant SDF-1. In a murine model of peripheral ischemia, systemic gene therapy with longevity-associated variant-BPIFB4 promotes the recruitment of hematopoietic stem cells, reparative vascularization, and reperfusion of the ischemic muscle. Longevity-associated variant-BPIFB4 may represent a novel therapeutic tool to fight endothelial dysfunction and promote vascular

Mitochondrial-Nuclear Epistasis: Implications for Human Aging and Longevity

PubMed Central

Tranah, Gregory

2010-01-01

There is substantial evidence that mitochondria are involved in the aging process. Mitochondrial function requires the coordinated expression of hundreds of nuclear genes and a few dozen mitochondrial genes, many of which have been associated with either extended or shortened life span. Impaired mitochondrial function resulting from mtDNA and nuclear DNA variation is likely to contribute to an imbalance in cellular energy homeostasis, increased vulnerability to oxidative stress, and an increased rate of cellular senescence and aging. The complex genetic architecture of mitochondria suggests that there may be an equally complex set of gene interactions (epistases) involving genetic variation in the nuclear and mitochondrial genomes. Results from Drosophila suggest that the effects of mtDNA haplotypes on longevity vary among different nuclear allelic backgrounds, which could account for the inconsistent associations that have been observed between mitochondrial DNA (mtDNA) haplogroups and survival in humans. A diversity of pathways may influence the way mitochondria and nuclear – mitochondrial interactions modulate longevity, including: oxidative phosphorylation; mitochondrial uncoupling; antioxidant defenses; mitochondrial fission and fusion; and sirtuin regulation of mitochondrial genes. We hypothesize that aging and longevity, as complex traits having a significant genetic component, are likely to be controlled by nuclear gene variants interacting with both inherited and somatic mtDNA variability. PMID:20601194

Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan.

PubMed

Schroeder, Elizabeth A; Shadel, Gerald S

2014-01-01

Mitochondrial DNA (mtDNA) exists in multiple copies per cell and is essential for oxidative phosphorylation. Depleted or mutated mtDNA promotes numerous human diseases and may contribute to aging. Reduced TORC1 signaling in the budding yeast, Saccharomyces cerevisiae, extends chronological lifespan (CLS) in part by generating a mitochondrial ROS (mtROS) signal that epigenetically alters nuclear gene expression. To address the potential requirement for mtDNA maintenance in this response, we analyzed strains lacking the mitochondrial base-excision repair enzyme Ntg1p. Extension of CLS by mtROS signaling and reduced TORC1 activity, but not caloric restriction, was abrogated in ntg1Δ strains that exhibited mtDNA depletion without defects in respiration. The DNA damage response (DDR) kinase Rad53p, which transduces pro-longevity mtROS signals, is also activated in ntg1Δ strains. Restoring mtDNA copy number alleviated Rad53p activation and re-established CLS extension following mtROS signaling, indicating that Rad53p senses mtDNA depletion directly. Finally, DDR kinases regulate nucleus-mitochondria localization dynamics of Ntg1p. From these results, we conclude that the DDR pathway senses and may regulate Ntg1p-dependent mtDNA stability. Furthermore, Rad53p senses multiple mitochondrial stresses in a hierarchical manner to elicit specific physiological outcomes, exemplified by mtDNA depletion overriding the ability of Rad53p to transduce an adaptive mtROS longevity signal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Life History Traits of an Extended Longevity Phenotype of Drosophila melanogaster.

PubMed

Deepashree, S; Shivanandappa, T; Ramesh, S R

2017-01-01

Aging or senescence is a complex biological phenomenon. Artificially selected Drosophila for extended longevity is one of the experimental models used to understand the mechanisms involved in aging and to test various theories. To examine the life history traits and biochemical defenses in relation to aging in an extended longevity phenotype of Drosophila melanogaster. Life history traits viz., survivability, fecundity, development time, dry weight, wing size, lipid content, starvation, desiccation and cold resistances, locomotory ability, antioxidant enzyme activities and reactive oxygen species level between control and selected lines of D. melanogaster were investigated. In our model of Drosophila, extended longevity is associated with no trade-off in fecundity and shows variable resistance to environmental stress such as starvation, cold and desiccation. Enhanced biochemical defense involving the antioxidant enzymes was positively correlated with longevity. Extended longevity phenotypes of Drosophila represent genomic plasticity associated with variable life history traits attributed to the genetic background of the progenitor population and the environment of selection. Oxidative stress resistance seems to be a significant factor in longevity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Developmental stability, age at onset of foraging and longevity of Africanized honey bees (Apis mellifera L.) under heat stress (Hymenoptera: Apidae).

PubMed

Medina, Rubén G; Paxton, Robert J; De Luna, Efraín; Fleites-Ayil, Fernando A; Medina Medina, Luis A; Quezada-Euán, José Javier G

2018-05-01

Beekeeping with the western honey bee (Apis mellifera) is important in tropical regions but scant information is available on the possible consequences of global warming for tropical beekeeping. We evaluated the effect of heat stress on developmental stability, the age at onset of foraging (AOF) and longevity in Africanized honey bees (AHBs) in the Yucatan Peninsula of Mexico, one of the main honey producing areas in the Neotropics, where high temperatures occur in spring and summer. To do so, we reared worker AHB pupae under a fluctuating temperature regime, simulating current tropical heatwaves, with a high temperature peak of 40.0 °C for 1 h daily across six days, and compared them to control pupae reared at stable temperatures of 34.0-35.5 °C. Heat stress did not markedly affect overall body size, though the forewing of heat-stressed bees was slightly shorter than controls. However, bees reared under heat stress showed significantly greater fluctuating asymmetry (FA) in forewing shape. Heat stress also decreased AOF and reduced longevity. Our results show that changes occur in the phenotype and behavior of honey bees under heat stress, with potential consequences for colony fitness. Copyright © 2018 Elsevier Ltd. All rights reserved.

A comparative cellular and molecular biology of longevity database.

PubMed

Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

2013-10-01

Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

PubMed Central

Moskalev, Alexey A.; Smit-McBride, Zeljka; Shaposhnikov, Mikhail V.; Plyusnina, Ekaterina N.; Zhavoronkov, Alex; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E.

2013-01-01

The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions. PMID:21986581

[Environmental factors of longevity].

PubMed

Christen, Yves

2003-03-01

A PROBABLE ROLE: The great increase in life expectancy over the past decades and too short a time lapse for any major genetic mutations to intervene, are arguments in favour of the intervention of environmental factors in longevity. A FAIRLY LONG LIST: Various environmental factors can be envisaged: prenatal environment, pollution, radiation and oncogenic agents, notably tobacco, food (quantitatively and qualitatively), medicinal products, stress, education and socio-professional life style, isolation, number of children and sexual activity, sports and exercising, etc. It is highly likely that all these factors, or at least some of them, have a real effect on longevity, although this is difficult to demonstrate directly. A COMBINED EFFECT: The basic idea of this paper is that these environmental factors should be seen as agents, the effects of which would be combined with those of genetic factors, considered as agents of radically different nature. We suggest that, in order to have any real effect, these environmental factors have to work on the same cell mechanisms as those that affect the genetic process, notably the mechanisms related to oxidative stress and genetic expression.

The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity

PubMed Central

Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C.; Riedel, Christian G.; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R.; Riera, Celine E.; Lillemeier, Bjorn F.; Kemphues, Kenneth; Yates, John R.; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

2015-01-01

SUMMARY One of the major determinants of aging in organisms ranging from worms to man are FOXO family transcription factors, which are downstream effectors of Insulin/IGF-1 signaling (IIS). The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. PMID:26154057

Selection for longevity confers resistance to low-temperature stress in Drosophila melanogaster.

PubMed

Luckinbill, L S

1998-03-01

One theory of the evolution of longevity says that improvement in life span is dependent on an increased ability to resist environmental stresses of all kind. Selective breeding of Drosophila melanogaster populations for longevity has demonstrably increased life span and also altered a number of other traits, such as resistance to starvation, desiccation, and ethanol fumes, and the ability to sustain longer flight. While the exact physiologic basis of some of these traits is not yet fully understood, at least some are known to derive from the properties of metabolic substrates of glycolysis. Improvement in those characters can depend partially, therefore, on altered stores of metabolites created from glycogen. Based on the known general relationship of some traits and the suspected basis in metabolism of others, we examine the possibility here that increased life span is accompanied by other traits that also confer physiologic resistance to stress. Specifically, we test the prediction that long-lived populations of fruit flies should be more resistant to low (prefreezing) and freezing temperature extremes. Both selected and control populations were found to be susceptible to prefreezing (1.5 degrees C) and freezing temperatures (0 degree C) here, but adults and pupae of the long-lived populations generally survived better in both situations, and at all durations of exposure. The resistance of individuals improved with acclimatization, but was superior in the long-lived populations whether thermal decline was rapid or stepwise. Cold resistant, long-lived populations also had significantly higher in vitro levels of glycerol, a cryoprotectant metabolite produced from glycogen. However, while adults and pupae of long-lived stocks were more resistant to cold, larvae of those stocks were more sensitive and survived relatively poorly at every length of exposure and acclimation. This surprising result implies that larvae maintain lower levels of cryoprotectant substances

Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

PubMed

Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

2016-02-26

The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

PubMed Central

Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

2016-01-01

The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

Floral longevity and autonomous selfing are altered by pollination and water availability in Collinsia heterophylla.

PubMed

Jorgensen, Rachael; Arathi, H S

2013-09-01

A plant investing in reproduction partitions resources between flowering and seed production. Under resource limitation, altered allocations may result in floral trait variations, leading to compromised fecundity. Floral longevity and timing of selfing are often the traits most likely to be affected. The duration of corolla retention determines whether fecundity results from outcrossing or by delayed selfing-mediated reproductive assurance. In this study, the role of pollination schedules and soil water availability on floral longevity and seed production is tested in Collinsia heterophylla (Plantaginaceae). Using three different watering regimes and pollination schedules, effects on floral longevity and seed production were studied in this protandrous, flowering annual. The results reveal that soil water status and pollination together influence floral longevity with low soil water and hand-pollinations early in the floral lifespan reducing longevity. However, early pollinations under excess water did not extend longevity, implying that resource surplus does not lengthen the outcrossing period. The results also indicate that pollen receipt, a reliable cue for fecundity, accelerates flower drop. Early corolla abscission under drought stress could potentially exacerbate sexual conflict in this protandrous, hermaphroditic species by ensuring self-pollen paternity and enabling male control of floral longevity. While pollination schedules did not affect fecundity, water stress reduced per-capita seed numbers. Unmanipulated flowers underwent delayed autonomous selfing, producing very few seeds, suggesting that inbreeding depression may limit benefits of selfing. In plants where herkogamy and dichogamy facilitate outcrossing, floral longevity determines reproductive success and mating system. Reduction in longevity under drought suggests a strong environmental effect that could potentially alter the preferred breeding mode in this mixed-mated species. Extrapolating the

Hypothalamic and dietary control of temperature-mediated longevity

PubMed Central

Tabarean, Iustin; Morrison, Brad; Marcondes, Maria Cecilia; Bartfai, Tamas; Conti, Bruno

2009-01-01

Temperature is an important modulator of longevity and aging in both poikilotherms and homeotherm animals. In homeotherms, temperature homeostasis is regulated primarily in the preoptic area (POA) of the hypothalamus. This region receives and integrates peripheral, central and environmental signals and maintains a nearly constant core body temperature (Tcore) by regulating the autonomic and hormonal control of heat production and heat dissipation. Temperature sensitive neurons found in the POA are considered key elements of the neuronal circuitry modulating these effects. Nutrient homeostasis is also a hypothalamically regulated modulator of aging as well as one of the signals that can influence Tcore in homeotherms. Investigating the mechanisms of the regulation of nutrient and temperature homeostasis in the hypothalamus is important to understand how these two elements of energy homeostasis influence longevity and aging as well as how aging can affect hypothalamic homeostatic mechanisms. PMID:19631766

Blood miRNomes and transcriptomes reveal novel longevity mechanisms in the long-lived bat, Myotis myotis.

PubMed

Huang, Zixia; Jebb, David; Teeling, Emma C

2016-11-10

Chiroptera, the bats, are the only order of mammals capable of true self-powered flight. Bats exhibit a number of other exceptional traits such as echolocation, viral tolerance and, perhaps most puzzlingly, extreme longevity given their body size. Little is known about the molecular mechanisms driving their extended longevity particularly at the levels of gene expression and post-transcriptional regulation. To elucidate the molecular mechanisms that may underlie their unusual longevity, we have deep sequenced 246.5 million small RNA reads from whole blood of the long-lived greater mouse-eared bats, Myotis myotis, and conducted a series of genome-wide comparative analyses between bat and non-bat mammals (human, pig and cow) in both blood miRNomes and transcriptomes, for the first time. We identified 539 miRNA gene candidates from bats, of which 468 unique mature miRNA were obtained. More than half of these miRNA (65.1 %) were regarded as bat-specific, regulating genes involved in the immune, ageing and tumorigenesis pathways. We have also developed a stringent pipeline for genome-wide miRNome comparisons across species, and identified 37 orthologous miRNA groups shared with bat, human, pig and cow, 6 of which were differentially expressed. For bats, 3 out of 4 up-regulated miRNA (miR-101-3p, miR-16-5p, miR-143-3p) likely function as tumor suppressors against various kinds of cancers, while one down-regulated miRNA (miR-221-5p) acts as a tumorigenesis promoter in human breast and pancreatic cancers. Additionally, a genome-wide comparison of mRNA transcriptomes across species also revealed specific gene expression patterns in bats. 127 up-regulated genes were enriched mainly in mitotic cell cycle and DNA repair mechanisms, while 364 down-regulated genes were involved primarily in mitochondrial activity. Our comprehensive and integrative analyses revealed bat-specific and differentially expressed miRNA and mRNA that function in key longevity pathways, producing a

Selection for sow longevity.

PubMed

Serenius, T; Stalder, K J

2006-04-01

Sow longevity plays an important role in economically efficient piglet production because sow longevity is related to the number of piglets produced during its productive lifetime; however, selection for sow longevity is not commonly practiced in any pig breeding program. There is relatively little scientific literature concerning the genetic parameters (genetic variation and genetic correlations) or methods available for breeding value estimation for effective selection for sow longevity. This paper summarizes the current knowledge about the genetics of sow longevity and discusses the available breeding value estimation methods for sow longevity traits. The studies in the literature clearly indicate that sow longevity is a complex trait, and even the definition of sow longevity is variable depending on the researcher and research objective. In general, the measures and analyses of sow longevity can be divided into 1) continuous traits (e.g., productive lifetime) analyzed with proportional hazard models; and 2) more simple binary traits such as stayability until some predetermined fixed parity. Most studies have concluded that sufficient genetic variation exists for effective selection on sow longevity, and heritability estimates have ranged between 0.02 and 0.25. Moreover, sow longevity has shown to be genetically associated with prolificacy and leg conformation traits. Variable results from previous research have led to a lack of consensus among swine breeders concerning the valid methodology of estimating breeding values for longevity traits. One can not deny the superiority of survival analysis in the modeling approach of longevity data; however, multiple-trait analyses are not possible using currently available survival analysis software. Less sophisticated approaches have the advantage of evaluating multiple traits simultaneously, and thus, can use the genetic associations between sow longevity and other traits. Additional research is needed to identify the

Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions.

PubMed

Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A; Oei, Nicole Y; Cobbaert, Christa M; Ballieux, Bart E; van der Grond, Jeroen; Westendorp, Rudi G; Pijl, Hanno; van Heemst, Diana

2015-01-01

The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls). During 24 h, venous blood was sampled every 10 minutes for determination of circulatory ACTH and cortisol concentrations. Deconvolution analysis, cross approximate entropy analysis and ACTH-cortisol-dose response modeling were used to assess, respectively, ACTH and cortisol secretion parameters, feedforward and feedback synchrony and adrenal gland ACTH responsivity. Mean (95% Confidence Interval) basal ACTH secretion was higher in male offspring compared to male controls (645 (324-1286) ngl/L/24 h versus 240 (120-477) ng/L/24 h, P = 0.05). Other ACTH and cortisol secretion parameters did not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups. These results suggest that familial longevity is not associated with major differences in HPA-axis activity under resting conditions, although modest, sex-specific differences may exist between groups that might be clinically relevant.

Hypothalamic and dietary control of temperature-mediated longevity.

PubMed

Tabarean, Iustin; Morrison, Brad; Marcondes, Maria Cecilia; Bartfai, Tamas; Conti, Bruno

2010-01-01

Temperature is an important modulator of longevity and aging in both poikilotherms and homeotherm animals. In homeotherms, temperature homeostasis is regulated primarily in the preoptic area (POA) of the hypothalamus. This region receives and integrates peripheral, central and environmental signals and maintains a nearly constant core body temperature (T(core)) by regulating the autonomic and hormonal control of heat production and heat dissipation. Temperature sensitive neurons found in the POA are considered key elements of the neuronal circuitry modulating these effects. Nutrient homeostasis is also a hypothalamically regulated modulator of aging as well as one of the signals that can influence T(core) in homeotherms. Investigating the mechanisms of the regulation of nutrient and temperature homeostasis in the hypothalamus is important to understanding how these two elements of energy homeostasis influence longevity and aging as well as how aging can affect hypothalamic homeostatic mechanisms. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Induction of Cytoprotective Pathways Is Central to the Extension of Lifespan Conferred by Multiple Longevity Pathways

PubMed Central

Shore, David E.; Carr, Christopher E.; Ruvkun, Gary

2012-01-01

Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60), the ER UPR (hsp-4), ROS response (sod-3, gst-4), and xenobiotic detoxification (gst-4). We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors. PMID:22829775

A regulatory network-based approach dissects late maturation processes related to the acquisition of desiccation tolerance and longevity of Medicago truncatula seeds.

PubMed

Verdier, Jerome; Lalanne, David; Pelletier, Sandra; Torres-Jerez, Ivone; Righetti, Karima; Bandyopadhyay, Kaustav; Leprince, Olivier; Chatelain, Emilie; Vu, Benoit Ly; Gouzy, Jerome; Gamas, Pascal; Udvardi, Michael K; Buitink, Julia

2013-10-01

In seeds, desiccation tolerance (DT) and the ability to survive the dry state for prolonged periods of time (longevity) are two essential traits for seed quality that are consecutively acquired during maturation. Using transcriptomic and metabolomic profiling together with a conditional-dependent network of global transcription interactions, we dissected the maturation events from the end of seed filling to final maturation drying during the last 3 weeks of seed development in Medicago truncatula. The network revealed distinct coexpression modules related to the acquisition of DT, longevity, and pod abscission. The acquisition of DT and dormancy module was associated with abiotic stress response genes, including late embryogenesis abundant (LEA) genes. The longevity module was enriched in genes involved in RNA processing and translation. Concomitantly, LEA polypeptides accumulated, displaying an 18-d delayed accumulation compared with transcripts. During maturation, gulose and stachyose levels increased and correlated with longevity. A seed-specific network identified known and putative transcriptional regulators of DT, including ABSCISIC ACID-INSENSITIVE3 (MtABI3), MtABI4, MtABI5, and APETALA2/ ETHYLENE RESPONSE ELEMENT BINDING PROTEIN (AtAP2/EREBP) transcription factor as major hubs. These transcriptional activators were highly connected to LEA genes. Longevity genes were highly connected to two MtAP2/EREBP and two basic leucine zipper transcription factors. A heat shock factor was found at the transition of DT and longevity modules, connecting to both gene sets. Gain- and loss-of-function approaches of MtABI3 confirmed 80% of its predicted targets, thereby experimentally validating the network. This study captures the coordinated regulation of seed maturation and identifies distinct regulatory networks underlying the preparation for the dry and quiescent states.

Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans.

PubMed

Honda, Yoko; Higashibata, Akira; Matsunaga, Yohei; Yonezawa, Yukiko; Kawano, Tsuyoshi; Higashitani, Atsushi; Kuriyama, Kana; Shimazu, Toru; Tanaka, Masashi; Szewczyk, Nathaniel J; Ishioka, Noriaki; Honda, Shuji

2012-01-01

How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues.

Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans

PubMed Central

Honda, Yoko; Higashibata, Akira; Matsunaga, Yohei; Yonezawa, Yukiko; Kawano, Tsuyoshi; Higashitani, Atsushi; Kuriyama, Kana; Shimazu, Toru; Tanaka, Masashi; Szewczyk, Nathaniel J.; Ishioka, Noriaki; Honda, Shuji

2012-01-01

How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues. PMID:22768380

Co-overexpression of two Heat Shock Factors results in enhanced seed longevity and in synergistic effects on seedling tolerance to severe dehydration and oxidative stress.

PubMed

Personat, José-María; Tejedor-Cano, Javier; Prieto-Dapena, Pilar; Almoguera, Concepción; Jordano, Juan

2014-03-04

We have previously reported that the seed-specific overexpression of sunflower (Helianthus annuus L.) Heat Shock Factor A9 (HaHSFA9) enhanced seed longevity in transgenic tobacco (Nicotiana tabacum L.). In addition, the overexpression of HaHSFA9 in vegetative organs conferred tolerance to drastic levels of dehydration and oxidative stress. Here we found that the combined overexpression of sunflower Heat Shock Factor A4a (HaHSFA4a) and HaHSFA9 enhanced all the previously reported phenotypes described for the overexpression of HaHSFA9 alone. The improved phenotypes occurred in coincidence with only subtle changes in the accumulation of small Heat Shock Proteins (sHSP) that are encoded by genes activated by HaHSFA9. The single overexpression of HaHSFA4a in vegetative organs (which lack endogenous HSFA9 proteins) did not induce sHSP accumulation under control growth conditions; neither it conferred thermotolerance. The overexpression of HaHSFA4a alone also failed to induce tolerance to severe abiotic stress. Thus, a synergistic functional effect of both factors was evident in seedlings. Our study revealed that HaHSFA4a requires HaHSFA9 for in planta function. Our results strongly support the involvement of HaHSFA4a and HaHSFA9 in transcriptional co-activation of a genetic program of longevity and desiccation tolerance in sunflower seeds. These results would also have potential application for improving seed longevity and tolerance to severe stress in vegetative organs.

The Epidemiology of Longevity and Exceptional Survival

PubMed Central

Newman, Anne B.; Murabito, Joanne M.

2013-01-01

The field of the “epidemiology of longevity” has been expanding rapidly in recent years. Several long-term cohort studies have followed older adults long enough to identify the most long-lived and to define many factors that lead to a long life span. Very long-lived people such as centenarians have been examined using case-control study designs. Both cohort and case-control studies have been the subject of genome-wide association studies that have identified genetic variants associated with longevity. With growing recognition of the importance of rare variations, family studies of longevity will be useful. Most recently, exome and whole-genome sequencing, gene expression, and epigenetic studies have been undertaken to better define functional variation and regulation of the genome. In this review, we consider how these studies are leading to a deeper understanding of the underlying biologic pathways to longevity. PMID:23372024

Beneficial influences of systemic cooperation and sociological behavior on longevity.

PubMed

Mountz, John D; Zant, Gary Van; Allison, David B; Zhang, Huang-Ge; Hsu, Hui-Chen

2002-04-30

During his long research career in the field of aging, Dr Bernard Strehler developed a series of theories concerning the identity of genes that can promote longevity and their role in natural selection. As a tribute to Dr Strehler, we have taken this opportunity to summarize a selection of these theories and to illustrate how these insights have influenced our search for longevity genes within the immune system. The identification of longevity genes has proven difficult. We believe that, at least in part, this reflects the emphasis on the concept of survival of the 'physically' fittest. We have used the immune system as a model to demonstrate that, over and above the self-evident advantage of those genes that contribute the attributes commonly associated with survival of the 'physically' fittest, those genes that lead to a predisposition to cooperate also confer a competitive survival advantage. As the acquisition of cooperativity in a society is linked to support mechanisms provided by older individuals, the search for longevity genes should not be limited to those genes that are associated with extended expression of a youthful phenotype. Rather these studies should be expanded to include identification of those genes that regulate physiologic parameters that affect individual longevity, even if they do not correspond with the traditional view of reproductive competitiveness. At the societal level, longevity genes may encode attributes that regulate sociologic or psychological parameters that may contribute to a tendency to non-aggressive or cooperative behavior that leads to achievement of common goals necessary for the survival of the species. This view of the selection for longevity impacts the analysis of longevity genes and aging at the organismal level. Dr Strehler viewed organismal aging as an integrated functional state, in which he conceived the outcome as reflecting the net balance of functional decrementers and evolved compensatory features. We propose

Small nucleoli are a cellular hallmark of longevity

PubMed Central

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H. Eka. D.; Müller, Roman-Ulrich; Slagboom, P. Eline; Partridge, Linda; Antebi, Adam

2017-01-01

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa. PMID:28853436

Small nucleoli are a cellular hallmark of longevity.

PubMed

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H Eka D; Müller, Roman-Ulrich; Slagboom, P Eline; Partridge, Linda; Antebi, Adam

2016-08-30

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

Positive Feedback between Transcriptional and Kinase Suppression in Nematodes with Extraordinary Longevity and Stress Resistance

PubMed Central

Bharill, Puneet; Shmookler Reis, Robert J.

2009-01-01

Insulin/IGF-1 signaling (IIS) regulates development and metabolism, and modulates aging, of Caenorhabditis elegans. In nematodes, as in mammals, IIS is understood to operate through a kinase-phosphorylation cascade that inactivates the DAF-16/FOXO transcription factor. Situated at the center of this pathway, phosphatidylinositol 3-kinase (PI3K) phosphorylates PIP2 to form PIP3, a phospholipid required for membrane tethering and activation of many signaling molecules. Nonsense mutants of age-1, the nematode gene encoding the class-I catalytic subunit of PI3K, produce only a truncated protein lacking the kinase domain, and yet confer 10-fold greater longevity on second-generation (F2) homozygotes, and comparable gains in stress resistance. Their F1 parents, like weaker age-1 mutants, are far less robust—implying that maternally contributed trace amounts of PI3K activity or of PIP3 block the extreme age-1 phenotypes. We find that F2-mutant adults have <10% of wild-type kinase activity in vitro and <60% of normal phosphoprotein levels in vivo. Inactivation of PI3K not only disrupts PIP3-dependent kinase signaling, but surprisingly also attenuates transcripts of numerous IIS components, even upstream of PI3K, and those of signaling molecules that cross-talk with IIS. The age-1(mg44) nonsense mutation results, in F2 adults, in changes to kinase profiles and to expression levels of multiple transcripts that distinguish this mutant from F1 age-1 homozygotes, a weaker age-1 mutant, or wild-type adults. Most but not all of those changes are reversed by a second mutation to daf-16, implicating both DAF-16/ FOXO–dependent and –independent mechanisms. RNAi, silencing genes that are downregulated in long-lived worms, improves oxidative-stress resistance of wild-type adults. It is therefore plausible that attenuation of those genes in age-1(mg44)-F2 adults contributes to their exceptional survival. IIS in nematodes (and presumably in other species) thus involves

Longevity and aging. Role of free radicals and xanthine oxidase. A review.

PubMed

Labat-Robert, J; Robert, L

2014-04-01

Longevity and aging are differently regulated. Longevity has an important part of genetic determinants, aging is essentially post-genetic. Among the genes involved in longevity determination, sirtuins, activated also by calorie restriction and some others as the TOR pathway, attracted special interest after the insulin–IGF pathway first shown to regulate longevity in model organisms. For most of these genes, postponement of life-threatening diseases is the basis of their action which never exceeds about 35% of all determinants, in humans. Among the post-genetic mechanisms responsible for age-related decline of function, free radicals attracted early interest as well as the Maillard reaction, generating also free radicals. Most attempts to remediate to free radical damage failed however, although different scavenger mechanisms and protective substances are present in the organism. Synthetic protectors were also tested without success. The only example of a successful treatment of a free radical mediated pathology is the case of xanthine oxidase, involved in cardiovascular pathology, essentially during the ischemia-reperfusion process. Its inhibition by allopurinol is currently used to fight this deadly syndrome.

Environmental conditions can modulate the links among oxidative stress, age, and longevity.

PubMed

Marasco, Valeria; Stier, Antoine; Boner, Winnie; Griffiths, Kate; Heidinger, Britt; Monaghan, Pat

2017-06-01

Understanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early- and mid-adulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2'-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age-related change. Copyright © 2017 Elsevier B.V. All rights reserved.

Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

2016-04-01

Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

Molecular aspects of flower senescence and strategies to improve flower longevity

PubMed Central

Shibuya, Kenichi

2018-01-01

Flower longevity is one of the most important traits for ornamental plants. Ethylene plays a crucial role in flower senescence in some plant species. In several species that show ethylene-dependent flower senescence, genetic modification targeting genes for ethylene biosynthesis or signaling has improved flower longevity. Although little is known about regulatory mechanisms of petal senescence in flowers that show ethylene-independent senescence, a recent study of Japanese morning glory revealed that a NAC transcription factor, EPHEMERAL1 (EPH1), is a key regulator in ethylene-independent petal senescence. EPH1 is induced in an age-dependent manner irrespective of ethylene signal, and suppression of EPH1 expression dramatically delays petal senescence. In ethylene-dependent petal senescence, comprehensive transcriptome analyses revealed the involvement of transcription factors, a basic helix-loop-helix protein and a homeodomain-leucine zipper protein, in the transcriptional regulation of the ethylene biosynthesis enzymes. This review summarizes molecular aspects of flower senescence and discusses strategies to improve flower longevity by molecular breeding. PMID:29681752

BLISTER Regulates Polycomb-Target Genes, Represses Stress-Regulated Genes and Promotes Stress Responses in Arabidopsis thaliana.

PubMed

Kleinmanns, Julia A; Schatlowski, Nicole; Heckmann, David; Schubert, Daniel

2017-01-01

HIGHLIGHTS The PRC2 interacting protein BLISTER likely acts downstream of PRC2 to silence Polycomb target genes and is a key regulator of specific stress responses in Arabidopsis . Polycomb group (PcG) proteins are key epigenetic regulators of development. The highly conserved Polycomb repressive complex 2 (PRC2) represses thousands of target genes by trimethylating H3K27 (H3K27me3). Plant specific PcG components and functions are largely unknown, however, we previously identified the plant-specific protein BLISTER (BLI) as a PRC2 interactor. BLI regulates PcG target genes and promotes cold stress resistance. To further understand the function of BLI , we analyzed the transcriptional profile of bli-1 mutants. Approximately 40% of the up-regulated genes in bli are PcG target genes, however, bli-1 mutants did not show changes in H3K27me3 levels at all tested genes, indicating that BLI regulates PcG target genes downstream of or in parallel to PRC2. Interestingly, a significant number of BLI regulated H3K27me3 target genes is regulated by the stress hormone absciscic acid (ABA). We further reveal an overrepresentation of genes responding to abiotic stresses such as drought, high salinity, or heat stress among the up-regulated genes in bli mutants. Consistently, bli mutants showed reduced desiccation stress tolerance. We conclude that the PRC2 associated protein BLI is a key regulator of stress-responsive genes in Arabidopsis : it represses ABA-responsive PcG target genes, likely downstream of PRC2, and promotes resistance to several stresses such as cold and drought.

Positive selection of Caenorhabditis elegans mutants with increased stress resistance and longevity.

PubMed Central

Muñoz, Manuel J; Riddle, Donald L

2003-01-01

We developed selective conditions for long-lived mutants of the nematode Caenorhabditis elegans by subjecting the first larval stage (L1) to thermal stress at 30 degrees for 7 days. The surviving larvae developed to fertile adults after the temperature was shifted to 15 degrees. A total of one million F(2) progeny and a half million F(3) progeny of ethyl-methanesulfonate-mutagenized animals were treated in three separate experiments. Among the 81 putative mutants that recovered and matured to the reproductive adult, 63 retested as thermotolerant and 49 (80%) exhibited a >15% increase in mean life span. All the known classes of dauer formation (Daf) mutant that affect longevity were found, including six new alleles of daf-2, and a unique temperature-sensitive, dauer-constitutive allele of age-1. Alleles of dyf-2 and unc-13 were isolated, and mutants of unc-18, a gene that interacts with unc-13, were also found to be long lived. Thirteen additional mutations define at least four new genes. PMID:12586705

Integrin-linked kinase modulates longevity and thermotolerance in C. elegans through neuronal control of HSF-1

PubMed Central

Kumsta, Caroline; Ching, Tsui-Ting; Nishimura, Mayuko; Davis, Andrew E; Gelino, Sara; Catan, Hannah H; Yu, Xiaokun; Chu, Chu-Chiao; Ong, Binnan; Panowski, Siler H; Baird, Nathan; Bodmer, Rolf; Hsu, Ao-Lin; Hansen, Malene

2014-01-01

Integrin-signaling complexes play important roles in cytoskeletal organization and cell adhesion in many species. Components of the integrin-signaling complex have been linked to aging in both Caenorhabditis elegans and Drosophila melanogaster, but the mechanism underlying this function is unknown. Here, we investigated the role of integrin-linked kinase (ILK), a key component of the integrin-signaling complex, in lifespan determination. We report that genetic reduction of ILK in both C. elegans and Drosophila increased resistance to heat stress, and led to lifespan extension in C. elegans without majorly affecting cytoskeletal integrity. In C. elegans, longevity and thermotolerance induced by ILK depletion was mediated by heat-shock factor-1 (HSF-1), a major transcriptional regulator of the heat-shock response (HSR). Reduction in ILK levels increased hsf-1 transcription and activation, and led to enhanced expression of a subset of genes with roles in the HSR. Moreover, induction of HSR-related genes, longevity and thermotolerance caused by ILK reduction required the thermosensory neurons AFD and interneurons AIY, which are known to play a critical role in the canonical HSR. Notably, ILK was expressed in neighboring neurons, but not in AFD or AIY, implying that ILK reduction initiates cell nonautonomous signaling through thermosensory neurons to elicit a noncanonical HSR. Our results thus identify HSF-1 as a novel effector of the organismal response to reduced ILK levels and show that ILK inhibition regulates HSF-1 in a cell nonautonomous fashion to enhance stress resistance and lifespan in C. elegans. PMID:24314125

Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.

PubMed

Goldberg, Alexander A; Richard, Vincent R; Kyryakov, Pavlo; Bourque, Simon D; Beach, Adam; Burstein, Michelle T; Glebov, Anastasia; Koupaki, Olivia; Boukh-Viner, Tatiana; Gregg, Christopher; Juneau, Mylène; English, Ann M; Thomas, David Y; Titorenko, Vladimir I

2010-07-01

In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA.

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity.

PubMed

Deprez, Marie-Anne; Eskes, Elja; Wilms, Tobias; Ludovico, Paula; Winderickx, Joris

2018-01-12

The plasma membrane H + -ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

Forever young: Mechanisms of natural anoxia tolerance and potential links to longevity

PubMed Central

Krivoruchko, Anastasia

2010-01-01

While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cyto-protective proteins. Turtles are also known for their incredible longevity and display characteristics of “negligible senescence.” We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity. PMID:20716943

Cognitive emotion regulation fails the stress test

PubMed Central

Raio, Candace M.; Orederu, Temidayo A.; Palazzolo, Laura; Shurick, Ashley A.; Phelps, Elizabeth A.

2013-01-01

Cognitive emotion regulation has been widely shown in the laboratory to be an effective way to alter the nature of emotional responses. Despite its success in experimental contexts, however, we often fail to use these strategies in everyday life where stress is pervasive. The successful execution of cognitive regulation relies on intact executive functioning and engagement of the prefrontal cortex, both of which are rapidly impaired by the deleterious effects of stress. Because it is specifically under stressful conditions that we may benefit most from such deliberate forms of emotion regulation, we tested the efficacy of cognitive regulation after stress exposure. Participants first underwent fear-conditioning, where they learned that one stimulus (CS+) predicted an aversive outcome but another predicted a neutral outcome (CS−). Cognitive regulation training directly followed where participants were taught to regulate fear responses to the aversive stimulus. The next day, participants underwent an acute stress induction or a control task before repeating the fear-conditioning task using these newly acquired regulation skills. Skin conductance served as an index of fear arousal, and salivary α-amylase and cortisol concentrations were assayed as neuroendocrine markers of stress response. Although groups showed no differences in fear arousal during initial fear learning, nonstressed participants demonstrated robust fear reduction following regulation training, whereas stressed participants showed no such reduction. Our results suggest that stress markedly impairs the cognitive regulation of emotion and highlights critical limitations of this technique to control affective responses under stress. PMID:23980142

A Regulatory Network-Based Approach Dissects Late Maturation Processes Related to the Acquisition of Desiccation Tolerance and Longevity of Medicago truncatula Seeds1[C][W][OPEN

PubMed Central

Verdier, Jerome; Lalanne, David; Pelletier, Sandra; Torres-Jerez, Ivone; Righetti, Karima; Bandyopadhyay, Kaustav; Leprince, Olivier; Chatelain, Emilie; Vu, Benoit Ly; Gouzy, Jerome; Gamas, Pascal; Udvardi, Michael K.; Buitink, Julia

2013-01-01

In seeds, desiccation tolerance (DT) and the ability to survive the dry state for prolonged periods of time (longevity) are two essential traits for seed quality that are consecutively acquired during maturation. Using transcriptomic and metabolomic profiling together with a conditional-dependent network of global transcription interactions, we dissected the maturation events from the end of seed filling to final maturation drying during the last 3 weeks of seed development in Medicago truncatula. The network revealed distinct coexpression modules related to the acquisition of DT, longevity, and pod abscission. The acquisition of DT and dormancy module was associated with abiotic stress response genes, including late embryogenesis abundant (LEA) genes. The longevity module was enriched in genes involved in RNA processing and translation. Concomitantly, LEA polypeptides accumulated, displaying an 18-d delayed accumulation compared with transcripts. During maturation, gulose and stachyose levels increased and correlated with longevity. A seed-specific network identified known and putative transcriptional regulators of DT, including ABSCISIC ACID-INSENSITIVE3 (MtABI3), MtABI4, MtABI5, and APETALA2/ ETHYLENE RESPONSE ELEMENT BINDING PROTEIN (AtAP2/EREBP) transcription factor as major hubs. These transcriptional activators were highly connected to LEA genes. Longevity genes were highly connected to two MtAP2/EREBP and two basic leucine zipper transcription factors. A heat shock factor was found at the transition of DT and longevity modules, connecting to both gene sets. Gain- and loss-of-function approaches of MtABI3 confirmed 80% of its predicted targets, thereby experimentally validating the network. This study captures the coordinated regulation of seed maturation and identifies distinct regulatory networks underlying the preparation for the dry and quiescent states. PMID:23929721

How the Effects of Aging and Stresses of Life Are Integrated in Mortality Rates: Insights for Genetic Studies of Human Health and Longevity

PubMed Central

Yashin, Anatoliy I.; Arbeev, Konstantin G.; Arbeeva, Liubov S.; Wu, Deqing; Akushevich, Igor; Kovtun, Mikhail; Yashkin, Arseniy; Kulminski, Alexander; Culminskaya, Irina; Stallard, Eric; Li, Miaozhu; Ukraintseva, Svetlana V.

2015-01-01

Background Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a major cause of age related health declines then postponing aging could be an efficient strategy for improving the health of the elderly. Implementing this strategy requires a better understanding of genetic and non-genetic connections among aging, health, and longevity. Data and methods We review progress and problems in research areas whose development may contribute to analyses of such connections. These include genetic studies of human aging and longevity, the heterogeneity of populations with respect to their susceptibility to disease and death, forces that shape age patterns of human mortality, secular trends in mortality decline, and integrative mortality modeling using longitudinal data. Results The dynamic involvement of genetic factors in (i) morbidity/mortality risks, (ii) responses to stresses of life, (iii) multi-morbidities of many elderly individuals, (iv) trade-offs for diseases, (v) genetic heterogeneity, and (vi) other relevant aging-related health declines, underscores the need for a comprehensive, integrated approach to analyze the genetic connections for all of the above aspects of aging-related changes. Conclusion The dynamic relationships among aging, health, and longevity traits would be better understood if one linked several research fields within one conceptual framework that allowed for efficient analyses of available longitudinal data using the wealth of available knowledge about aging, health, and longevity already accumulated in the research field. PMID:26280653

Nitrogen and carbon source balance determines longevity, independently of fermentative or respiratory metabolism in the yeast Saccharomyces cerevisiae.

PubMed

Santos, Júlia; Leitão-Correia, Fernanda; Sousa, Maria João; Leão, Cecília

2016-04-26

Dietary regimens have proven to delay aging and age-associated diseases in several eukaryotic model organisms but the input of nutritional balance to longevity regulation is still poorly understood. Here, we present data on the role of single carbon and nitrogen sources and their interplay in yeast longevity. Data demonstrate that ammonium, a rich nitrogen source, decreases chronological life span (CLS) of the prototrophic Saccharomyces cerevisiae strain PYCC 4072 in a concentration-dependent manner and, accordingly, that CLS can be extended through ammonium restriction, even in conditions of initial glucose abundance. We further show that CLS extension depends on initial ammonium and glucose concentrations in the growth medium, as long as other nutrients are not limiting. Glutamine, another rich nitrogen source, induced CLS shortening similarly to ammonium, but this effect was not observed with the poor nitrogen source urea. Ammonium decreased yeast CLS independently of the metabolic process activated during aging, either respiration or fermentation, and induced replication stress inhibiting a proper cell cycle arrest in G0/G1 phase. The present results shade new light on the nutritional equilibrium as a key factor on cell longevity and may contribute for the definition of interventions to promote life span and healthy aging.

Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans

PubMed Central

Lin, Yen-Hung; Chen, Yi-Chun; Kao, Tzu-Yu; Lin, Yi-Chun; Hsu, Tzu-En; Wu, Yi-Chun; Ja, William W; Brummel, Theodore J; Kapahi, Pankaj; Yuh, Chiou-Hwa; Yu, Lin-Kwei; Lin, Zhi-Han; You, Ru-Jing; Jhong, Yi-Ting; Wang, Horng-Dar

2014-01-01

Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unknown. DAG is metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn-glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl-1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S6K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging. PMID:24889782

MicroRNA Predictors of Longevity in Caenorhabditis elegans

PubMed Central

Pincus, Zachary; Smith-Vikos, Thalyana; Slack, Frank J.

2011-01-01

Neither genetic nor environmental factors fully account for variability in individual longevity: genetically identical invertebrates in homogenous environments often experience no less variability in lifespan than outbred human populations. Such variability is often assumed to result from stochasticity in damage accumulation over time; however, the identification of early-life gene expression states that predict future longevity would suggest that lifespan is least in part epigenetically determined. Such “biomarkers of aging,” genetic or otherwise, nevertheless remain rare. In this work, we sought early-life differences in organismal robustness in unperturbed individuals and examined the utility of microRNAs, known regulators of lifespan, development, and robustness, as aging biomarkers. We quantitatively examined Caenorhabditis elegans reared individually in a novel apparatus and observed throughout their lives. Early-to-mid–adulthood measures of homeostatic ability jointly predict 62% of longevity variability. Though correlated, markers of growth/muscle maintenance and of metabolic by-products (“age pigments”) report independently on lifespan, suggesting that graceful aging is not a single process. We further identified three microRNAs in which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti-correlates. Two of these three microRNA “biomarkers of aging” act upstream in insulin/IGF-1–like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan. PMID:21980307

Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

PubMed

Bai, Hua; Post, Stephanie; Kang, Ping; Tatar, Marc

2015-01-01

Mutations of the insulin/IGF signaling (IIS) pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1). Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP) is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP). Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

Molecular characterization of the acquisition of longevity during seed maturation in soybean

PubMed Central

Lalanne, David; Rossi, Rubiana Falopa; Pelletier, Sandra; da Silva, Edvaldo Aparecido Amaral

2017-01-01

Seed longevity, defined as the ability to remain alive during storage, is an important agronomic factor. Poor longevity negatively impacts seedling establishment and consequently crop yield. This is particularly problematic for soybean as seeds have a short lifespan. While the economic importance of soybean has fueled a large number of transcriptome studies during embryogenesis and seed filling, the mechanisms regulating seed longevity during late maturation remain poorly understood. Here, a detailed physiological and molecular characterization of late seed maturation was performed in soybean to obtain a comprehensive overview of the regulatory genes that are potentially involved in longevity. Longevity appeared at physiological maturity at the end of seed filling before maturation drying and progressively doubled until the seeds reached the dry state. The increase in longevity was associated with the expression of genes encoding protective chaperones such as heat shock proteins and the repression of nuclear and chloroplast genes involved in a range of chloroplast activities, including photosynthesis. An increase in the raffinose family oligosaccharides (RFO)/sucrose ratio together with changes in RFO metabolism genes was also associated with longevity. A gene co-expression network analysis revealed 27 transcription factors whose expression profiles were highly correlated with longevity. Eight of them were previously identified in the longevity network of Medicago truncatula, including homologues of ERF110, HSF6AB, NFXL1 and members of the DREB2 family. The network also contained several transcription factors associated with auxin and developmental cell fate during flowering, organ growth and differentiation. A transcriptional transition occurred concomitant with seed chlorophyll loss and detachment from the mother plant, suggesting the activation of a post-abscission program. This transition was enriched with AP2/EREBP and WRKY transcription factors and genes

A family longevity selection score: ranking sibships by their longevity, size, and availability for study.

PubMed

Sebastiani, Paola; Hadley, Evan C; Province, Michael; Christensen, Kaare; Rossi, Winifred; Perls, Thomas T; Ash, Arlene S

2009-12-15

Family studies of exceptional longevity can potentially identify genetic and other factors contributing to long life and healthy aging. Although such studies seek families that are exceptionally long lived, they also need living members who can provide DNA and phenotype information. On the basis of these considerations, the authors developed a metric to rank families for selection into a family study of longevity. Their measure, the family longevity selection score (FLoSS), is the sum of 2 components: 1) an estimated family longevity score built from birth-, gender-, and nation-specific cohort survival probabilities and 2) a bonus for older living siblings. The authors examined properties of FLoSS-based family rankings by using data from 3 ongoing studies: the New England Centenarian Study, the Framingham Heart Study, and screenees for the Long Life Family Study. FLoSS-based selection yields families with exceptional longevity, satisfactory sibship sizes and numbers of living siblings, and high ages. Parameters in the FLoSS formula can be tailored for studies of specific populations or age ranges or with different conditions. The first component of the FLoSS also provides a conceptually sound survival measure to characterize exceptional longevity in individuals or families in various types of studies and correlates well with later-observed longevity.

Telomeres, Nutrition, and Longevity: Can We Really Navigate Our Aging?

PubMed

Vidacek, Nikolina Škrobot; Nanic, Lucia; Ravlic, Sanda; Sopta, Mary; Geric, Marko; Gajski, Goran; Garaj-Vrhovac, Vera; Rubelj, Ivica

2017-12-12

Telomeres are dynamic chromosome-end structures that serve as guardians of genome stability. They are known to be one of the major determinants of aging and longevity in higher mammals. Studies have demonstrated a direct correlation between telomere length and life expectancy, stress, DNA damage, and onset of aging-related diseases. This review discusses the most important factors that influence our telomeres. Various genetic and environmental factors such as diet, physical activity, obesity, and stress are known to influence health and longevity as well as telomere dynamics. Individuals currently have the opportunity to modulate the dynamics of their aging and health span, monitor these processes, and even make future projections by following their telomere dynamics. As telomeres react to positive as well as negative health factors, we should be able to directly influence our telomere metabolism, slow their deterioration, and diminish our aging and perhaps extend our life and health span. © The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Exercise, Aging and Longevity.

ERIC Educational Resources Information Center

Brown, Stanley P.; Cundiff, David E.

1988-01-01

The question of whether or not a lifelong program of exercise actually has a bearing on longevity is discussed. The effects of exercise on the aging process, and the longevity-exercise relationship are reviewed. The conflicting evidence on the subject is presented. (JL)

A C. elegans Thermosensory Circuit Regulates Longevity through crh-1/CREB-Dependent flp-6 Neuropeptide Signaling.

PubMed

Chen, Yen-Chih; Chen, Hung-Jhen; Tseng, Wei-Chin; Hsu, Jiun-Min; Huang, Tzu-Ting; Chen, Chun-Hao; Pan, Chun-Liang

2016-10-24

Sensory perception, including thermosensation, shapes longevity in diverse organisms, but longevity-modulating signals from the sensory neurons are largely obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD thermosensory neuron is a key mechanism that maintains lifespan at warm temperatures in C. elegans. In response to temperature rise and crh-1 activation, the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1 and FLP-6 are necessary and sufficient for longevity at warm temperatures. Our data suggest that FLP-6 targets the AIY interneurons and engages DAF-9 sterol hormone signaling. Moreover, we show that FLP-6 signaling downregulates ins-7/insulin-like peptide and several insulin pathway genes, whose activity compromises lifespan. Our work illustrates how temperature experience is integrated by the thermosensory circuit to generate neuropeptide signals that remodel insulin and sterol hormone signaling and reveals a neuronal-endocrine circuit driven by thermosensation to promote temperature-specific longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Interspecific correlation between red blood cell mitochondrial ROS production, cardiolipin content and longevity in birds.

PubMed

Delhaye, Jessica; Salamin, Nicolas; Roulin, Alexandre; Criscuolo, François; Bize, Pierre; Christe, Philippe

2016-12-01

Mitochondrial respiration releases reactive oxygen species (ROS) as by-products that can damage the soma and may in turn accelerate ageing. Hence, according to "the oxidative stress theory of ageing", longer-lived organisms may have evolved mechanisms that improve mitochondrial function, reduce ROS production and/or increase cell resistance to oxidative damage. Cardiolipin, an important mitochondrial inner-membrane phospholipid, has these properties by binding and stabilizing mitochondrial inner-membrane proteins. Here, we investigated whether ROS production, cardiolipin content and cell membrane resistance to oxidative attack in freshly collected red blood cells (RBCs) are associated with longevity (range 5-35 years) in 21 bird species belonging to seven Orders. After controlling for phylogeny, body size and oxygen consumption, variation in maximum longevity was significantly explained by mitochondrial ROS production and cardiolipin content, but not by membrane resistance to oxidative attack. RBCs of longer-lived species produced less ROS and contained more cardiolipin than RBCs of shorter-lived species did. These results support the oxidative stress theory of ageing and shed light on mitochondrial cardiolipin as an important factor linking ROS production to longevity.

Predictors of Exceptional Longevity: Effects of Early-Life and Midlife Conditions, and Familial Longevity.

PubMed

Gavrilov, Leonid A; Gavrilova, Natalia S

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890-1891 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are occupation as a farmer at age 40, Northeastern region of birth in the United States, and birth in the second half of year. A gender-specific predictor of female longevity is the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880-1895. We found that male gender of centenarian has a significant positive effect on survival of adult male relatives (brothers and fathers) but not female blood relatives. Life span of centenarian siblings-in-law is lower compared to life span of centenarian siblings and does not depend on centenarian gender. Wives of male centenarians (who share lifestyle and living conditions) have a significantly better survival

Predictors of Exceptional Longevity: Effects of Early-Life and Midlife Conditions, and Familial Longevity

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2015-01-01

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890–1891 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are occupation as a farmer at age 40, Northeastern region of birth in the United States, and birth in the second half of year. A gender-specific predictor of female longevity is the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880–1895. We found that male gender of centenarian has a significant positive effect on survival of adult male relatives (brothers and fathers) but not female blood relatives. Life span of centenarian siblings-in-law is lower compared to life span of centenarian siblings and does not depend on centenarian gender. Wives of male centenarians (who share lifestyle and living conditions) have a significantly better survival

NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting.

PubMed

Goh, Grace Y S; Winter, Johnathan J; Bhanshali, Forum; Doering, Kelsie R S; Lai, Regina; Lee, Kayoung; Veal, Elizabeth A; Taubert, Stefan

2018-06-01

Endogenous and exogenous stresses elicit transcriptional responses that limit damage and promote cell/organismal survival. Like its mammalian counterparts, hepatocyte nuclear factor 4 (HNF4) and peroxisome proliferator-activated receptor α (PPARα), Caenorhabditis elegans NHR-49 is a well-established regulator of lipid metabolism. Here, we reveal that NHR-49 is essential to activate a transcriptional response common to organic peroxide and fasting, which includes the pro-longevity gene fmo-2/flavin-containing monooxygenase. These NHR-49-dependent, stress-responsive genes are also upregulated in long-lived glp-1/notch receptor mutants, with two of them making critical contributions to the oxidative stress resistance of wild-type and long-lived glp-1 mutants worms. Similar to its role in lipid metabolism, NHR-49 requires the mediator subunit mdt-15 to promote stress-induced gene expression. However, NHR-49 acts independently from the transcription factor hlh-30/TFEB that also promotes fmo-2 expression. We show that activation of the p38 MAPK, PMK-1, which is important for adaptation to a variety of stresses, is also important for peroxide-induced expression of a subset of NHR-49-dependent genes that includes fmo-2. However, organic peroxide increases NHR-49 protein levels, by a posttranscriptional mechanism that does not require PMK-1 activation. Together, these findings establish a new role for the HNF4/PPARα-related NHR-49 as a stress-activated regulator of cytoprotective gene expression. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast.

PubMed

Campos, Sergio E; Avelar-Rivas, J Abraham; Garay, Erika; Juárez-Reyes, Alejandro; DeLuna, Alexander

2018-06-01

Dietary restriction is arguably the most promising nonpharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other regulatory factors are involved. Here, we measured at the genomewide level the chronological lifespan of Saccharomyces cerevisiae gene deletion strains under two nitrogen source regimens, glutamine (nonrestricted) and γ-aminobutyric acid (restricted). We identified 473 mutants with diminished or enhanced extension of lifespan. Functional analysis of such dietary restriction genes revealed novel processes underlying longevity by the nitrogen source quality, which also allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary restriction response. Importantly, deletions of transcription factors Msn2, Msn4, Snf6, Tec1, and Ste12 resulted in diminished lifespan extension and defects in cell cycle arrest upon nutrient starvation, suggesting that regulation of the cell cycle is a major mechanism of chronological longevity. We further show that STE12 overexpression is enough to extend lifespan, linking the pheromone/invasive growth pathway with cell survivorship. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans.

PubMed

Luciani, Genna M; Magomedova, Lilia; Puckrin, Rachel; Urbanus, Malene L; Wallace, Iain M; Giaever, Guri; Nislow, Corey; Cummins, Carolyn L; Roy, Peter J

2011-11-06

The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals.

Comparative study of physico-chemical parameters of drinking water from some longevity and non-longevity areas of China.

PubMed

Du, Yajun; Luo, Kunli; Hussain, Rahib

2017-06-01

There is an obvious regional longevity phenomenon in China and many longevity counties are located in South China. This study was carried out to find the characteristics of elemental contents of drinking water in longevity areas in South China and the differences to non-longevity areas in China. A total of 128 drinking water samples were collected from longevity areas in South China (n = 40), non-longevity areas in South China (n = 74) and non-longevity areas in North China (n = 14) and 46 parameters of water were determined or calculated. The results showed that drinking water in longevity areas of South China had a high ratio of sum concentration of essential micro-elements in sum concentration of micro-elements (SCME) and a low ratio of sum concentration of hazardous micro-elements in SCME. The concentration of total hardness (TH) and strontium in drinking water was 157.82 mg/L and 82.1 μg/L, respectively, and they were 14.61 mg/L, 7.45 μg/L and 291.69 mg/L, 748.65 μg/L in the non-longevity areas of South and North China, respectively. The study concluded that drinking water containing 157.82 mg/L TH and 82.1 μg/L strontium in South China may be optimum to human health.

Longevity extension of worker honey bees (Apis mellifera) by royal jelly: optimal dose and active ingredient

PubMed Central

Han, Mingfeng

2017-01-01

In the Western honey bee, Apis mellifera, queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ) as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution, and developed a method of obtaining long lived workers. We then compared the effects of longevity extension by RJ 4% with bee-collected pollen from rapeseed (Brassica napus). Lastly, we determined that a water soluble RJ protein obtained by precipitation with 60% ammonium sulfate (RJP60) contained the main component for longevity extension after comparing the effects of RJ crude protein extract (RJCP), RJP30 (obtained by precipitation with 30% ammonium sulfate), and RJ ethanol extract (RJEE). Understanding what regulates worker longevity has potential to help increase colony productivity and improve crop pollination efficiency. PMID:28367370

Longevity extension of worker honey bees (Apis mellifera) by royal jelly: optimal dose and active ingredient.

PubMed

Yang, Wenchao; Tian, Yuanyuan; Han, Mingfeng; Miao, Xiaoqing

2017-01-01

In the Western honey bee, Apis mellifera , queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ) as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution, and developed a method of obtaining long lived workers. We then compared the effects of longevity extension by RJ 4% with bee-collected pollen from rapeseed ( Brassica napus ). Lastly, we determined that a water soluble RJ protein obtained by precipitation with 60% ammonium sulfate (RJP 60 ) contained the main component for longevity extension after comparing the effects of RJ crude protein extract (RJCP), RJP 30 (obtained by precipitation with 30% ammonium sulfate), and RJ ethanol extract (RJEE). Understanding what regulates worker longevity has potential to help increase colony productivity and improve crop pollination efficiency.

Endurance exercise and selective breeding for longevity extend Drosophila healthspan by overlapping mechanisms.

PubMed

Sujkowski, Alyson; Bazzell, Brian; Carpenter, Kylie; Arking, Robert; Wessells, Robert J

2015-08-01

Endurance exercise has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. In addition, long-term exercise reduces the incidence of age-related diseases in humans and in model organisms. Despite these evident benefits, the genetic pathways required for exercise interventions to achieve these effects are still relatively poorly understood. Here, we compare gene expression changes during endurance training in Drosophila melanogaster to gene expression changes during selective breeding for longevity. Microarrays indicate that 65% of gene expression changes found in flies selectively bred for longevity are also found in flies subjected to three weeks of exercise training. We find that both selective breeding and endurance training increase endurance, cardiac performance, running speed, flying height, and levels of autophagy in adipose tissue. Both interventions generally upregulate stress defense, folate metabolism, and lipase activity, while downregulating carbohydrate metabolism and odorant receptor expression. Several members of the methuselah-like (mthl) gene family are downregulated by both interventions. Knockdown of mthl-3 was sufficient to provide extension of negative geotaxis behavior, endurance and cardiac stress resistance. These results provide support for endurance exercise as a broadly acting anti-aging intervention and confirm that exercise training acts in part by targeting longevity assurance pathways.

Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response.

PubMed

Wang, Chen; Skinner, Craig; Easlon, Erin; Lin, Su-Ju

2009-12-01

Enhanced stress response has been suggested to promote longevity in many species. Calorie restriction (CR) and conserved nutrient-sensing target of rapamycin (TOR) and protein kinase A (PKA) pathways have also been suggested to extend life span by increasing stress response, which protects cells from age-dependent accumulation of oxidative damages. Here we show that deleting the yeast 14-3-3 protein, Bmh1, extends chronological life span (CLS) by activating the stress response. 14-3-3 proteins are highly conserved chaperone-like proteins that play important roles in many cellular processes. bmh1Delta-induced heat resistance and CLS extension require the general stress-response transcription factors Msn2, Msn4, and Rim15. The bmh1Delta mutant also displays a decreased reactive oxygen species level and increased heat-shock-element-driven transcription activity. We also show that BMH1 genetically interacts with CR and conserved nutrient-sensing TOR- and PKA-signaling pathways to regulate life span. Interestingly, the level of phosphorylated Ser238 on Bmh1 increases during chronological aging, which is delayed by CR or by reduced TOR activities. In addition, we demonstrate that PKA can directly phosphorylate Ser238 on Bmh1. The status of Bmh1 phosphorylation is therefore likely to play important roles in life-span regulation. Together, our studies suggest that phosphorylated Bmh1 may cause inhibitory effects on downstream longevity factors, including stress-response proteins. Deleting Bmh1 may eliminate the inhibitory effects of Bmh1 on these longevity factors and therefore extends life span.

Relationships among Environment, Climate, and Longevity in China

PubMed Central

Huang, Yi; Rosenberg, Mark; Hou, Lingli; Hu, Mengjin

2017-01-01

Human longevity is influenced by environment and nutrition. We considered environmental and nutritional factors relating to longevity in Chinese cities. We found higher 85+/65+ distribution ratios, indicating enhanced longevity, in the coastal and southern regions of China. These areas also featured higher humidity, low standard deviation of monthly temperature, higher levels of selenium (Se) distribution in soil, and greater sea fish consumption. Moderate climate is more conducive to longevity, however, there is no significant difference in longevity between different sub-climatic types within moderate climate; the relation between humidity and longevity is not always positive, the relation between altitude and longevity is not always negative. Nutritional factors like Se and omega-3 fatty acids contained in sea fish were crucial to longevity. In contrast, the consumption of meat and freshwater fish were less related to longevity. Taken together, humidity, altitude, and per capita sea fish consumption, when evaluated via geographically weighted regression, explained 66% and 68% of longevity among Chinese individuals in 2000 and 2010, respectively. Other factors require further discussion. PMID:28991186

Relationships among Environment, Climate, and Longevity in China.

PubMed

Huang, Yi; Rosenberg, Mark; Hou, Lingli; Hu, Mengjin

2017-10-08

Human longevity is influenced by environment and nutrition. We considered environmental and nutritional factors relating to longevity in Chinese cities. We found higher 85+/65+ distribution ratios, indicating enhanced longevity, in the coastal and southern regions of China. These areas also featured higher humidity, low standard deviation of monthly temperature, higher levels of selenium (Se) distribution in soil, and greater sea fish consumption. Moderate climate is more conducive to longevity, however, there is no significant difference in longevity between different sub-climatic types within moderate climate; the relation between humidity and longevity is not always positive, the relation between altitude and longevity is not always negative. Nutritional factors like Se and omega-3 fatty acids contained in sea fish were crucial to longevity. In contrast, the consumption of meat and freshwater fish were less related to longevity. Taken together, humidity, altitude, and per capita sea fish consumption, when evaluated via geographically weighted regression, explained 66% and 68% of longevity among Chinese individuals in 2000 and 2010, respectively. Other factors require further discussion.

Induction of autophagy by spermidine promotes longevity.

PubMed

Eisenberg, Tobias; Knauer, Heide; Schauer, Alexandra; Büttner, Sabrina; Ruckenstuhl, Christoph; Carmona-Gutierrez, Didac; Ring, Julia; Schroeder, Sabrina; Magnes, Christoph; Antonacci, Lucia; Fussi, Heike; Deszcz, Luiza; Hartl, Regina; Schraml, Elisabeth; Criollo, Alfredo; Megalou, Evgenia; Weiskopf, Daniela; Laun, Peter; Heeren, Gino; Breitenbach, Michael; Grubeck-Loebenstein, Beatrix; Herker, Eva; Fahrenkrog, Birthe; Fröhlich, Kai-Uwe; Sinner, Frank; Tavernarakis, Nektarios; Minois, Nadege; Kroemer, Guido; Madeo, Frank

2009-11-01

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

Increased total DNA damage and oxidative stress in brain are associated with decreased longevity in high sucrose diet fed WNIN/Gr-Ob obese rats.

PubMed

Potukuchi, Aruna; Addepally, Uma; Sindhu, Kirankumar; Manchala, Raghunath

2017-06-01

Obesity and Type 2 Diabetes (T2D) are chronic nutrient-related disorders that occur together and pose a grave burden to society. They are among the most common causes of ageing and death. Obesity and T2D per se accelerate ageing albeit the underlying mechanisms are unclear yet. Also, it is not clear whether or not superimposing T2D on obesity accelerates ageing. Present study validated the hypothesis, 'super-imposing T2D on obesity accelerates ageing' in WNIN/Gr-Ob, the impaired glucose tolerant, obese rat as the model and evaluated probable underlying mechanisms. To estimate the survival analysis of WNIN/Gr-Ob rats induced with T2D. To determine the extent of DNA damage and oxidative stress in the brain, the master controller of the body, in WNIN/Gr-Ob rats with/without high sucrose induced T2D/aggravation of insulin resistance (IR) after 3 and 6 months of feeding. T2D was induced/IR was aggravated by feeding high sucrose diet (HSD) to 9-10 weeks old, male WNIN/Gr-Ob rats. Survival percentage was determined statistically by Kaplan-Meier estimator. Neuronal DNA damage was quantified by the Comet assay while the oxidative stress and antioxidant status were evaluated from the levels of malonaldialdehyde, reduced glutathione, and superoxide dismutase (SOD) activity. HSD feeding decreased longevity of WNIN/Gr-Ob rats and was associated with significantly higher total neuronal DNA damage after three months of feeding but not later. In line with this was the increased neuronal oxidative stress (lipid peroxidation) and decreased antioxidant status (reduced glutathione and SOD activity) in HSD than Starch-based diet (SBD) fed rats. The results suggest that HSD feeding decreased the longevity of WNIN/Gr-Ob obese rats probably by increasing oxidative stress and aggravating IR, a condition that precedes T2D.

Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity.

PubMed

Ma, Siming; Upneja, Akhil; Galecki, Andrzej; Tsai, Yi-Miau; Burant, Charles F; Raskind, Sasha; Zhang, Quanwei; Zhang, Zhengdong D; Seluanov, Andrei; Gorbunova, Vera; Clish, Clary B; Miller, Richard A; Gladyshev, Vadim N

2016-11-22

Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites correlating with species longevity. Cells from longer lived species up-regulated genes involved in DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and showed high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in longevity across mammals at the level of global gene expression and metabolite levels and reveals pathways that define these differences.

Genome-Wide Analysis of Germline Signaling Genes Regulating Longevity and Innate Immunity in the Nematode Pristionchus pacificus

PubMed Central

Sommer, Ralf J.

2012-01-01

Removal of the reproductive system of many animals including fish, flies, nematodes, mice and humans can increase lifespan through mechanisms largely unknown. The abrogation of the germline in Caenorhabditis elegans increases longevity by 60% due to a signal emitted from the somatic gonad. Apart from increased longevity, germline-less C. elegans is also resistant to other environmental stressors such as feeding on bacterial pathogens. However, the evolutionary conservation of this pathogen resistance, its genetic basis and an understanding of genes involved in producing this extraordinary survival phenotype are currently unknown. To study these evolutionary aspects we used the necromenic nematode Pristionchus pacificus, which is a genetic model system used in comparison to C. elegans. By ablation of germline precursor cells and subsequent feeding on the pathogen Serratia marcescens we discovered that P. pacificus shows remarkable resistance to bacterial pathogens and that this response is evolutionarily conserved across the Genus Pristionchus. To gain a mechanistic understanding of the increased resistance to bacterial pathogens and longevity in germline-ablated P. pacificus we used whole genome microarrays to profile the transcriptional response comparing germline ablated versus un-ablated animals when fed S. marcescens. We show that lipid metabolism, maintenance of the proteasome, insulin signaling and nuclear pore complexes are essential for germline deficient phenotypes with more than 3,300 genes being differentially expressed. In contrast, gene expression of germline-less P. pacificus on E. coli (longevity) and S. marcescens (immunity) is very similar with only 244 genes differentially expressed indicating that longevity is due to abundant gene expression also involved in immunity. By testing existing mutants of Ppa-DAF-16/FOXO and the nuclear hormone receptor Ppa-DAF-12 we show a conserved function of both genes in resistance to bacterial pathogens and

Aging, longevity and health

PubMed Central

Rasmussen, Lene Juel; Sander, Miriam; Wewer, Ulla M.; Bohr, Vilhelm A.

2016-01-01

The IARU Congress on Aging, Longevity and Health, held on 5–7 October 2010 in Copenhagen, Denmark, was hosted by Rector Ralf Hemmingsen, University of Copenhagen and Dean Ulla Wewer, Faculty of Health Sciences, University of Copenhagen and was organized by Center for Healthy Aging (CEHA) under the leadership of CEHA Managing Director Lene Juel Rasmussen and Prof. Vilhelm Bohr, National Institute on Aging, NIH, Baltimore, USA (associated to CEHA). The Congress was attended by approximately 125 researchers interested in and/or conducting research on aging and aging-related topics. The opening Congress Session included speeches by Ralf Hemmingsen, Ulla Wewer, and Lene Juel Rasmussen and Keynote Addresses by four world renowned aging researchers: Povl Riis (The Age Forum), Bernard Jeune (University of Southern Denmark), George Martin (University of Washington, USA) and Jan Vijg (Albert Einstein School of Medicine, USA) as well as a lecture discussing the art-science interface by Thomas Söderqvist (Director, Medical Museion, University of Copenhagen). The topics of the first six Sessions of the Congress were: Neuroscience and DNA damage, Aging and Stress, Life Course, Environmental Factors and Neuroscience, Muscle and Life Span and Life Span and Mechanisms. Two additional Sessions highlighted ongoing research in the recently established Center for Healthy Aging at the University of Copenhagen. This report highlights outcomes of recent research on aging-related topics, as described at the IARU Congress on Aging, Longevity and Health. PMID:21820462

Aging, longevity and health.

PubMed

Rasmussen, Lene Juel; Sander, Miriam; Wewer, Ulla M; Bohr, Vilhelm A

2011-10-01

The IARU Congress on Aging, Longevity and Health, held on 5-7 October 2010 in Copenhagen, Denmark, was hosted by Rector Ralf Hemmingsen, University of Copenhagen and Dean Ulla Wewer, Faculty of Health Sciences, University of Copenhagen and was organized by Center for Healthy Aging (CEHA) under the leadership of CEHA Managing Director Lene Juel Rasmussen and Prof. Vilhelm Bohr, National Institute on Aging, NIH, Baltimore, USA (associated to CEHA). The Congress was attended by approximately 125 researchers interested in and/or conducting research on aging and aging-related topics. The opening Congress Session included speeches by Ralf Hemmingsen, Ulla Wewer, and Lene Juel Rasmussen and Keynote Addresses by four world renowned aging researchers: Povl Riis (The Age Forum), Bernard Jeune (University of Southern Denmark), George Martin (University of Washington, USA) and Jan Vijg (Albert Einstein School of Medicine, USA) as well as a lecture discussing the art-science interface by Thomas Söderqvist (Director, Medical Museion, University of Copenhagen). The topics of the first six Sessions of the Congress were: Neuroscience and DNA damage, Aging and Stress, Life Course, Environmental Factors and Neuroscience, Muscle and Life Span and Life Span and Mechanisms. Two additional Sessions highlighted ongoing research in the recently established Center for Healthy Aging at the University of Copenhagen. This report highlights outcomes of recent research on aging-related topics, as described at the IARU Congress on Aging, Longevity and Health. Copyright © 2011. Published by Elsevier Ireland Ltd.. All rights reserved.

Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster.

PubMed

Chattopadhyay, Debarati; Chitnis, Atith; Talekar, Aishwarya; Mulay, Prajakta; Makkar, Manyata; James, Joel; Thirumurugan, Kavitha

2017-06-01

Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals. In this study, we aimed to understand the effect of rutin on extending longevity in Drosophila melanogaster. Male and female flies were administered with a range of rutin doses (100-800 µM) to analyse whether rutin mediated lifespan-extension by hormesis. Effect of rutin on physiological parameters like food intake, fecundity, climbing activity, development and resistance to various stresses was also studied. Lifespan assays showed that rutin at 200 and 400 µM significantly extended median lifespan in both male and female flies beyond which flies exhibited drastically reduced longevity. Increase in survival at 400 µM was associated with reduced food intake and fecundity. Flies exhibited improved climbing capability with both 200 and 400 µM rutin. Flies fed with 100 and 200 µM rutin exhibited enhanced survival upon exposure to oxidative stress with 400 µM rutin exhibiting no improvement in median lifespan following oxidative stress. Analysis of endogenous peroxide upon treatment with rutin (100-400 µM) with or without 5% H 2 O 2 showed elevated levels of endogenous peroxide with 400 µM rutin whereas no increase in hydrogen peroxide level was observed with rutin at 100 and 200 µM. Finally, gene expression studies in male flies revealed that rutin treatment at 200 and/or 400 µM elevated transcript levels of dFoxO, MnSod, Cat, dTsc1, dTsc2, Thor, dAtg1, d

A role for seed storage proteins in Arabidopsis seed longevity

PubMed Central

Nguyen, Thu-Phuong; Cueff, Gwendal; Hegedus, Dwayne D; Rajjou, Loïc; Bentsink, Leónie

2015-01-01

Proteomics approaches have been a useful tool for determining the biological roles and functions of individual proteins and identifying the molecular mechanisms that govern seed germination, vigour and viability in response to ageing. In this work the dry seed proteome of four Arabidopsis thaliana genotypes, that carry introgression fragments at the position of seed longevity quantitative trait loci and as a result display different levels of seed longevity, was investigated. Seeds at two physiological states, after-ripened seeds that had the full germination ability and aged (stored) seeds of which the germination ability was severely reduced, were compared. Aged dry seed proteomes were markedly different from the after-ripened and reflected the seed longevity level of the four genotypes, despite the fact that dry seeds are metabolically quiescent. Results confirmed the role of antioxidant systems, notably vitamin E, and indicated that protection and maintenance of the translation machinery and energy pathways are essential for seed longevity. Moreover, a new role for seed storage proteins (SSPs) was identified in dry seeds during ageing. Cruciferins (CRUs) are the most abundant SSPs in Arabidopsis and seeds of a triple mutant for three CRU isoforms (crua crub cruc) were more sensitive to artificial ageing and their seed proteins were highly oxidized compared with wild-type seeds. These results confirm that oxidation is involved in seed deterioration and that SSPs buffer the seed from oxidative stress, thus protecting important proteins required for seed germination and seedling formation. PMID:26184996

Longevity of the Human Spaceflight Program

NASA Astrophysics Data System (ADS)

Gott, J. Richard

2007-02-01

The longevity of the human spaceflight program is important to our survival prospects. On May 27, 1993 I proposed a method for estimating future longevity, based on past observed longevity using the Copernican Principle: if your observation point is not special the 95% confidence level prediction of future longevity is between (1/39)th and 39 times the past longevity. The prediction for the future longevity of the human spaceflight program (then 32 years old) was greater than 10 months but less than 1248 years. We have already passed the lower limit. This Copernican formula has been tested a number of times, correctly predicting, among other things, future longevities of Broadway plays and musicals, and the Conservative Government in the United Kingdom. Recently, a study of future longevities of the 313 world leaders in power on May 27, 1993 has been completed. Assuming none still in office serve past age 100, the success rate of the 95% Copernican Formula is currently 94.55% with only one case (out of 313) left to be decided. The human spaceflight program has not been around long and so there is the danger its future will not be long enough to allow us to colonize off the earth. Policy implications are discussed. A smart plan would be to try to establish a self-supporting colony on Mars in the next 45 years. This should not require sending any more tons of material into space in the next 45 years than we have in the last 45 years.

Environmental control and control of the environment: the basis of longevity in bivalves.

PubMed

Abele, Doris; Philipp, Eva

2013-01-01

Longevity and ageing are two sides of a coin, leaving the question open as to which one is the cause and which one the effect. At the individual level, the physiological rate of ageing determines the length of life (= individual longevity, as long as death results from old age and not from disease or other impacts). Individual longevity depends on the direct influence of environmental conditions with respect to nutrition, and the possibility for and timing of reproduction, as well as on the energetic costs animals invest in behavioural and physiological stress defence. All these environmental effectors influence hormonal and cellular signalling pathways that modify the individual physiological condition, the reproductive strategy, and the rate of ageing. At the species level, longevity (= maximum lifespan) is the result of an evolutionary process and, thus, largely determined by the species' behavioural and physiological adaptations to its ecological niche. Specifically, reproductive and breeding strategies have to be optimized in relation to local environmental conditions in different habitats. As a result of adaptive and evolutionary processes, species longevity is genetically underpinned, not necessarily by a few ageing genes, but by an evolutionary process that has hierarchically shaped and optimized species genomes to function in a specific niche or environmental system. Importantly, investigations and reviews attempting to unravel the mechanistic basis of the ageing process need to differentiate clearly between the evolutionary process shaping longevity at the species level and the regulatory mechanisms that alter the individual rate of ageing. Copyright © 2012 S. Karger AG, Basel.

Biodemography of Exceptional Longevity: Early-life and Mid-life predictors of Human Longevity

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2011-01-01

Effects of early-life and middle-life conditions on exceptional longevity are explored in this study using two matched case-control studies. The first study compares 198 validated centenarians born in the United States in 1890-1893 to their shorter-lived siblings. Family histories of centenarians were reconstructed and exceptional longevity validated using early U.S. censuses, Social Security Administration Death Master File, state death indexes, online genealogies and other supplementary data resources. Siblings born to young mothers (<25 years) had significantly higher chances to live to 100 compared to siblings born to older mothers (odds ratio = 2.03, 95% CI = 1.33 - 3.11, P = 0.001) while paternal age and birth order were not associated with exceptional longevity. The second study explores whether people living to 100 and beyond are any different in physical characteristics at young age from their shorter-lived peers. A random representative sample of 240 men born in 1887 and survived to age 100 was selected from the US Social Security Administration database and linked to the US WWI civil draft registration cards collected in 1917 when these men were 30 years old. These validated centenarians were then compared to randomly selected controls matched by calendar year of birth, race and place of draft registration in 1917. It was found that ‘stout’ body build (being in the heaviest 15% of population) was negatively associated with survival to age 100 years. Farmer occupation and large number of children (4+) at age 30 increased the chances of exceptional longevity. Detailed description of dataset development, data cleaning procedure and validation of exceptional longevity is provided for both studies. These results demonstrate that matched case-control design is a useful approach in exploring effects of early-life conditions and middle-life characteristics on exceptional longevity. PMID:22582891

Longevity of HDPE Geomembranes in Geoenvironmental Applications

NASA Astrophysics Data System (ADS)

Ewais, Amr Mohamed Ragab Abdel Samad

With sufficient time, a high density polyethylene geomembrane will degrade and lose its engineering properties until ruptures signal the end of its service-life. This thesis examines the longevity of nine different geomembranes; five of them were of different thickness manufactured from the same resin. The degradation of properties and time to failure are investigated for geomembranes: in immersion tests; as a part of a landfill composite liner; and, exposed to the elements. The different thermal and stress histories associated with manufacturing geomembranes of different thickness are shown to affect their morphological structure; consequently, their stress crack resistance. When immersed in synthetic leachate, it was found that: (a) thicker geomembranes have a longer antioxidants depletion time but the effect of thickness decreases with temperature and is less than expected; (b) inferences of geomembrane's longevity based on its initial properties may be misleading because a geomembrane may chemically degrade (as manifested by the change in melt index) despite the presence of a significant amount of stabilizers (as manifested by the measured high pressure oxidative induction time); and, (c) stress crack resistance may change before antioxidant depletion or chemical degradation takes place, likely, due to changes in geomembrane morphological structure with the maximum decrease being observed at 55°C. Reductions also were measured for geomembrane immersed in air and water at 55°C. The geomembrane aged in a simulated landfill liner at 85°C is shown to have service-life as little as three years with 30,000 to >2.0 million ruptures/hectare at failure. For exposed geomembranes in Alumbrera (Argentina), samples were exhumed from two mine facilities after ~16 years of exposure. The antioxidants in exposed samples depleted to residual and the stress crack resistance had dropped to as low as 70 hours. Samples were exhumed from a different exposed geomembrane in a test

Emotion regulation: exploring the impact of stress and sex

PubMed Central

Kinner, Valerie L.; Het, Serkan; Wolf, Oliver T.

2014-01-01

Emotion regulation is a major prerequisite for adaptive behavior. The capacity to regulate emotions is particularly important during and after the encounter of a stressor. However, the impact of acute stress and its associated neuroendocrine alterations on emotion regulation have received little attention so far. This study aimed to explore how stress-induced cortisol increases affect three different emotion regulation strategies. Seventy two healthy men and women were either exposed to a stressor or a control condition. Subsequently participants viewed positive and negative images and were asked to up- or down-regulate their emotional responses or simultaneously required to solve an arithmetic task (distraction). The factors stress, sex, and strategy were operationalized as between group factors (n = 6 per cell). Stress caused an increase in blood pressure and higher subjective stress ratings. An increase in cortisol was observed in male participants only. In contrast to controls, stressed participants were less effective in distracting themselves from the emotional pictures. The results further suggest that in women stress enhances the ability to decrease negative emotions. These findings characterize the impact of stress and sex on emotion regulation and provide initial evidence that these factors may interact. PMID:25431554

Longevity and transposon defense, the case of termite reproductives

PubMed Central

Elsner, Daniel; Meusemann, Karen; Korb, Judith

2018-01-01

Social insects are promising new models in aging research. Within single colonies, longevity differences of several magnitudes exist that can be found elsewhere only between different species. Reproducing queens (and, in termites, also kings) can live for several decades, whereas sterile workers often have a lifespan of a few weeks only. We studied aging in the wild in a highly social insect, the termite Macrotermes bellicosus, which has one of the most pronounced longevity differences between reproductives and workers. We show that gene-expression patterns differed little between young and old reproductives, implying negligible aging. By contrast, old major workers had many genes up-regulated that are related to transposable elements (TEs), which can cause aging. Strikingly, genes from the PIWI-interacting RNA (piRNA) pathway, which are generally known to silence TEs in the germline of multicellular animals, were down-regulated only in old major workers but not in reproductives. Continued up-regulation of the piRNA defense commonly found in the germline of animals can explain the long life of termite reproductives, implying somatic cooption of germline defense during social evolution. This presents a striking germline/soma analogy as envisioned by the superorganism concept: the reproductives and workers of a colony reflect the germline and soma of multicellular animals, respectively. Our results provide support for the disposable soma theory of aging. PMID:29735660

The Homeobox Protein CEH-23 Mediates Prolonged Longevity in Response to Impaired Mitochondrial Electron Transport Chain in C. elegans

PubMed Central

Walter, Ludivine; Baruah, Aiswarya; Chang, Hsin-Wen; Pace, Heather Mae; Lee, Siu Sylvia

2011-01-01

Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC) can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases. PMID:21713031

77 FR 60948 - Stress Testing of Regulated Entities

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

... the stress test. F. Post-Assessment Actions by Regulated Entities--Proposed Sec. 1238.6 Section 1238.6... during each quarter of the stress test planning horizon, for each scenario: (1) Potential losses, pre... regulated by a primary federal financial regulatory agency, to conduct annual stress tests to determine...

NECTARINE PROMOTES LONGEVITY IN DROSOPHILA MELANOGASTER

PubMed Central

Boyd, Olga; Weng, Peter; Sun, Xiaoping; Alberico, Thomas; Laslo, Mara; Obenland, David M.; Kern, Bradley; Zou, Sige

2011-01-01

Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and healthspan. However, few fruits are known to improve the survival and healthspan in animals, let alone the underlying mechanisms. Here we investigate the effect of nectarine, a globally consumed fruit, on lifespan and healthspan in Drosophila melanogaster. Wild-type flies were fed the standard, dietary restriction (DR) or high fat diets supplemented with 0–4% nectarine extract. We measured lifespan, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-Hydroxynonenal-protein adduct in these flies. We also measured lifespan, locomotor activity and oxidative damage of sod1 mutant flies on the standard diet supplemented with 0–4% nectarine. Supplementation of 4% nectarine extended lifespan, increased fecundity and decreased expression of some metabolic genes, including a key gluconeogenesis gene PEPCK, and oxidative stress response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR or high fat diet. Nectarine reduced oxidative damage in wild-type females fed the high fat diet. Moreover, nectarine improved the survival and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and healthspan partly through modulating glucose metabolism and reducing oxidative damage. PMID:21406223

Daughters increase longevity of fathers, but daughters and sons equally reduce longevity of mothers.

PubMed

Jasienska, Grazyna; Nenko, Ilona; Jasienski, Michal

2006-01-01

Reproduction is energetically and physiologically expensive, and an individual investing resources into producing offspring should suffer costs such as deterioration in health condition and possibly shorter life span. Since the energetic and nutritional demands of pregnancy and breastfeeding render reproductive costs much higher in women than in men, women with a large number of children should show signs of deterioration in condition, while men with large families should not. However, whether reproductive costs reduce longevity in women is still questionable, and in men this issue has not been adequately addressed. In addition, since sons are energetically more expensive to produce than daughters, having sons should have a more pronounced negative impact on maternal longevity than having daughters. Here we document a striking disparity in the impact of children on the life span of mothers and fathers in a Polish rural population. We show for the first time that number of daughters was positively related to a longer life span of their fathers, increasing their longevity on average by 74 weeks per daughter born, while number of sons did not have a significant effect on paternal longevity. In contrast, in women, the number of daughters and number of sons reduced maternal longevity and did so to the same extent, on average by 95 weeks per son or daughter, indicating that for women, the costs of having sons and daughters are similar.

Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

PubMed Central

Samson, Eugenie; Arlia-Ciommo, Anthony; Dakik, Pamela; Cortes, Berly; Feldman, Rachel; Mohtashami, Sadaf; McAuley, Mélissa; Chancharoen, Marisa; Rukundo, Belise; Simard, Éric; Titorenko, Vladimir I.

2016-01-01

We discovered six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds. One of these extracts is the most potent longevity-extending pharmacological intervention yet described. We show that each of the six plant extracts is a geroprotector which delays the onset and decreases the rate of yeast chronological aging by eliciting a hormetic stress response. We also show that each of these extracts has different effects on cellular processes that define longevity in organisms across phyla. These effects include the following: 1) increased mitochondrial respiration and membrane potential; 2) augmented or reduced concentrations of reactive oxygen species; 3) decreased oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes; 4) enhanced cell resistance to oxidative and thermal stresses; and 5) accelerated degradation of neutral lipids deposited in lipid droplets. Our findings provide new insights into mechanisms through which chemicals extracted from certain plants can slow biological aging. PMID:26918729

SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson's disease.

PubMed

Singh, Preeti; Hanson, Peter S; Morris, Christopher M

2017-06-02

Sirtuins (SIRTs) are NAD + dependent lysine deacetylases which are conserved from bacteria to humans and have been associated with longevity and lifespan extension. SIRT1, the best studied mammalian SIRT is involved in many physiological and pathological processes and changes in SIRT1 have been implicated in neurodegenerative disorders, with SIRT1 having a suggested protective role in Parkinson's disease. In this study, we determined the effect of SIRT1 on cell survival and α-synuclein aggregate formation in SH-SY5Y cells following oxidative stress. Over-expression of SIRT1 protected SH-SY5Y cells from toxin induced cell death and the protection conferred by SIRT1 was partially independent of its deacetylase activity, which was associated with the repression of NF-кB and cPARP expression. SIRT1 reduced the formation of α-synuclein aggregates but showed minimal co-localisation with α-synuclein. In post-mortem brain tissue obtained from patients with Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies and Alzheimer's disease, the activity of SIRT1 was observed to be down-regulated. These findings suggests a negative effect of oxidative stress in neurodegenerative disorders and possibly explain the reduced activity of SIRT1 in neurodegenerative disorders. Our study shows that SIRT1 is a pro-survival protein that is downregulated under cellular stress.

Is There a Role for Oligosaccharides in Seed Longevity? An Assessment of Intracellular Glass Stability1

PubMed Central

Buitink, Julia; Hemminga, Marcus A.; Hoekstra, Folkert A.

2000-01-01

We examined whether oligosaccharides extend seed longevity by increasing the intracellular glass stability. For that purpose, we used a spin probe technique to measure the molecular mobility and glass transition temperature of the cytoplasm of impatiens (Impatiens walleriana) and bell pepper (Capsicum annuum) seeds that were osmo-primed to change oligosaccharide content and longevity. Using saturation transfer electron paramagnetic resonance spectroscopy, we found that the rotational correlation time of the polar spin probe 3-carboxy-proxyl in the cytoplasm decreased, together with longevity, as a function of increasing seed water content, suggesting that longevity may indeed be regulated by cytoplasmic mobility. Osmo-priming of the seeds resulted in considerable decreases in longevity and oligosaccharide content, while the sucrose content increased. No difference in the glass transition temperature was found between control and primed impatiens seeds at the same temperature and water content. Similarly, there was no difference in the rotational motion of the spin probe in the cytoplasm between control and primed impatiens and bell pepper seeds. We therefore conclude that oligosaccharides in seeds do not affect the stability of the intracellular glassy state, and that the reduced longevity after priming is not the result of increased molecular mobility in the cytoplasm. PMID:10759518

Visible light reduces C. elegans longevity.

PubMed

De Magalhaes Filho, C Daniel; Henriquez, Brian; Seah, Nicole E; Evans, Ronald M; Lapierre, Louis R; Dillin, Andrew

2018-03-02

The transparent nematode Caenorhabditis elegans can sense UV and blue-violet light to alter behavior. Because high-dose UV and blue-violet light are not a common feature outside of the laboratory setting, we asked what role, if any, could low-intensity visible light play in C. elegans physiology and longevity. Here, we show that C. elegans lifespan is inversely correlated to the time worms were exposed to visible light. While circadian control, lite-1 and tax-2 do not contribute to the lifespan reduction, we demonstrate that visible light creates photooxidative stress along with a general unfolded-protein response that decreases the lifespan. Finally, we find that long-lived mutants are more resistant to light stress, as well as wild-type worms supplemented pharmacologically with antioxidants. This study reveals that transparent nematodes are sensitive to visible light radiation and highlights the need to standardize methods for controlling the unrecognized biased effect of light during lifespan studies in laboratory conditions.

The homeodomain-interacting protein kinase HPK-1 preserves protein homeostasis and longevity through master regulatory control of the HSF-1 chaperone network and TORC1-restricted autophagy in Caenorhabditis elegans

PubMed Central

Morton, Elizabeth A.; Cornwell, Adam B.; Crick, Beresford; Lamitina, Todd; Douglas, Peter M.

2017-01-01

An extensive proteostatic network comprised of molecular chaperones and protein clearance mechanisms functions collectively to preserve the integrity and resiliency of the proteome. The efficacy of this network deteriorates during aging, coinciding with many clinical manifestations, including protein aggregation diseases of the nervous system. A decline in proteostasis can be delayed through the activation of cytoprotective transcriptional responses, which are sensitive to environmental stress and internal metabolic and physiological cues. The homeodomain-interacting protein kinase (hipk) family members are conserved transcriptional co-factors that have been implicated in both genotoxic and metabolic stress responses from yeast to mammals. We demonstrate that constitutive expression of the sole Caenorhabditis elegans Hipk homolog, hpk-1, is sufficient to delay aging, preserve proteostasis, and promote stress resistance, while loss of hpk-1 is deleterious to these phenotypes. We show that HPK-1 preserves proteostasis and extends longevity through distinct but complementary genetic pathways defined by the heat shock transcription factor (HSF-1), and the target of rapamycin complex 1 (TORC1). We demonstrate that HPK-1 antagonizes sumoylation of HSF-1, a post-translational modification associated with reduced transcriptional activity in mammals. We show that inhibition of sumoylation by RNAi enhances HSF-1-dependent transcriptional induction of chaperones in response to heat shock. We find that hpk-1 is required for HSF-1 to induce molecular chaperones after thermal stress and enhances hormetic extension of longevity. We also show that HPK-1 is required in conjunction with HSF-1 for maintenance of proteostasis in the absence of thermal stress, protecting against the formation of polyglutamine (Q35::YFP) protein aggregates and associated locomotory toxicity. These functions of HPK-1/HSF-1 undergo rapid down-regulation once animals reach reproductive maturity. We show

Social Support, Perceived Stress, and Markers of Heart Failure Severity

DTIC Science & Technology

2012-08-01

cardiovascular health and longevity became scientifically evident when epidemiologists encountered an intimate community of multigenerational Italian...on family cohesion, and the supportive nature of the community may have been protective against heart attacks and conducive to longevity " (Egolf...relationship linking stress with health. 16   Stress Definition and brief history Hans Selye (1950) — a major pioneer in the area of stress

Spatio-Temporal Variation of Longevity Clusters and the Influence of Social Development Level on Lifespan in a Chinese Longevous Area (1982–2010)

PubMed Central

Qin, Jian; Xia, Tianlong; Li, You; Liang, Xue; Wei, Peng; Long, Bingshuang; Lei, Mingzhi; Wei, Xiao; Tang, Xianyan; Zhang, Zhiyong

2017-01-01

The study aims to determine the spatial and temporal variation of a longevous region and explore the correlation between longevity and socioeconomic development. Population data at the township level were obtained from the last four population censuses (1982–2010). Five main lifespan indicators and the Human Development Index (HDI) were calculated. Getis-Ord G*, Gravity modeling, and Pearson’s r between lifespan indicators and HDI were applied. In this study, a stable longevous gathering area was discovered in Hechi during different periods. Under the influence of social and economic development, more longevous areas appeared. However, the effects of genetic and natural environmental factors on longevity were always dominant in this remote and mountainous city. Furthermore, longevity indicators lacked any significant correlation with life expectancy. No significant positive correlation was detected between lifespan indicators and HDI. Thus, we conclude that lifespan indicators can determine the spatial distribution and variation pattern of longevity from multiple dimensions. The geographical scope of longevity in Hechi City is gradually expanding, and significant spatial clustering was detected in southwestern, southern, and eastern parts of Hechi. This study also found that social economic development is likely to have a certain impact on new longevous areas, but their role on extreme longevity is not significant. PMID:28753971

The influence of acute stress on the regulation of conditioned fear

PubMed Central

Raio, Candace M.; Phelps, Elizabeth A.

2014-01-01

Fear learning and regulation is a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation), and briefly discuss other techniques (avoidance and reconsolidation) where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology. PMID:25530986

Increased survival and prolonged longevity mainly contribute to the temperature-adaptive evolutionary strategy in invasive Bemisia tabaci (Hemiptera: Aleyrodidae) Middle East Asia Minor 1.

PubMed

Lü, Zhi-Chuang; Gao, Qing-Lei; Wan, Fang-Hao; Yu, Hao; Guo, Jian-Ying

2014-10-15

With increasing global climate change, analyses of stress-inducing conditions have important significance in ecological adaptation and the biological distribution of species. To reveal the difference in temperature-adaptive strategy between Turpan and Beijing populations of Bemisia tabaci (Gennadius) Middle East Asia Minor 1 (MEAM1) under high-temperature stress conditions, we compared thermal tolerance and life history traits between Beijing and Turpan populations of MEAM1 after exposure to different heat shock treatments for different times. The experimental design reflected the nature of heat stress conditions suffered by MEAM1. The results showed that eggs, red-eyed pupae, and adults of the Turpan population were more heat tolerant than those of the Beijing population under the same stress conditions. Additionally, it was found that longevity and F1 adult survival rate were significantly higher in the Turpan population than in the Beijing population after heat shock stress, but egg number and F1 female ratio were not significantly different between Turpan population and Beijing population. Overall, it was suggested that heat tolerance and longevity traits were the most relevant for climate characteristics and not reproductive traits, and improved heat tolerance and prolonged longevity were important adaptive strategies that helped MEAM1 to survive in harsh high-temperature conditions such as Turpan arid desert climate. The present results provided further insight into the modes of heat tolerance and the ways in which survival and longevity traits respond to environmental selection pressures. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans

PubMed Central

Yang, Wen; Hekimi, Siegfried

2010-01-01

The nuo-6 and isp-1 genes of C. elegans encode, respectively, subunits of complex I and III of the mitochondrial respiratory chain. Partial loss-of-function mutations in these genes decrease electron transport and greatly increase the longevity of C. elegans by a mechanism that is distinct from that induced by reducing their level of expression by RNAi. Electron transport is a major source of the superoxide anion (O⋅ –), which in turn generates several types of toxic reactive oxygen species (ROS), and aging is accompanied by increased oxidative stress, which is an imbalance between the generation and detoxification of ROS. These observations have suggested that the longevity of such mitochondrial mutants might result from a reduction in ROS generation, which would be consistent with the mitochondrial oxidative stress theory of aging. It is difficult to measure ROS directly in living animals, and this has held back progress in determining their function in aging. Here we have adapted a technique of flow cytometry to directly measure ROS levels in isolated mitochondria to show that the generation of superoxide is elevated in the nuo-6 and isp-1 mitochondrial mutants, although overall ROS levels are not, and oxidative stress is low. Furthermore, we show that this elevation is necessary and sufficient to increase longevity, as it is abolished by the antioxidants NAC and vitamin C, and phenocopied by mild treatment with the prooxidant paraquat. Furthermore, the absence of effect of NAC and the additivity of the effect of paraquat on a variety of long- and short-lived mutants suggest that the pathway triggered by mitochondrial superoxide is distinct from previously studied mechanisms, including insulin signaling, dietary restriction, ubiquinone deficiency, the hypoxic response, and hormesis. These findings are not consistent with the mitochondrial oxidative stress theory of aging. Instead they show that increased superoxide generation acts as a signal in young mutant

Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress.

PubMed

Deegan, Shane; Saveljeva, Svetlana; Gorman, Adrienne M; Samali, Afshin

2013-07-01

Macroautophagy (autophagy) is a cellular catabolic process which can be described as a self-cannibalism. It serves as an essential protective response during conditions of endoplasmic reticulum (ER) stress through the bulk removal and degradation of unfolded proteins and damaged organelles; in particular, mitochondria (mitophagy) and ER (reticulophagy). Autophagy is genetically regulated and the autophagic machinery facilitates removal of damaged cell components and proteins; however, if the cell stress is acute or irreversible, cell death ensues. Despite these advances in the field, very little is known about how autophagy is initiated and how the autophagy machinery is transcriptionally regulated in response to ER stress. Some three dozen autophagy genes have been shown to be required for the correct assembly and function of the autophagic machinery; however; very little is known about how these genes are regulated by cellular stress. Here, we will review current knowledge regarding how ER stress and the unfolded protein response (UPR) induce autophagy, including description of the different autophagy-related genes which are regulated by the UPR.

Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity

PubMed Central

Sun, Liou Y.; Longo, Valter

2013-01-01

Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. Surprisingly, deficiency in GH signaling delays aging and remarkably extends longevity in laboratory mice. In GH-deficient and GH-resistant animals, the “healthspan” is also extended with delays in cognitive decline and in the onset of age-related disease. The role of hormones homologous to insulin-like growth factor (IGF, an important mediator of GH actions) in the control of aging and lifespan is evolutionarily conserved from worms to mammals with some homologies extending to unicellular yeast. The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Mechanisms responsible for delayed aging of GH-related mutants include enhanced stress resistance and xenobiotic metabolism, reduced inflammation, improved insulin signaling, and various metabolic adjustments. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species. However, there is yet no evidence of increased longevity in GH-resistant or GH-deficient humans, possibly due to non-age-related deaths. Results obtained in GH-related mutant mice provide striking examples of mutations of a single gene delaying aging, reducing age-related disease, and extending lifespan in a mammal and providing novel experimental systems for the study of mechanisms of aging. PMID:23589828

Stress Inducibility of SIRT1 and Its Role in Cytoprotection and Cancer

PubMed Central

Raynes, Rachel; Brunquell, Jessica

2013-01-01

Cells must continuously respond to stressful insults via the upregulation of cytoprotective pathways. The longevity factor and deacetylase SIRT1 plays a critical role in coordinating this cellular response to stress. SIRT1 activity and levels are regulated by cellular stressors, including metabolic, genotoxic, oxidative, and proteotoxic stress. As a stress sensor, SIRT1 impacts cell survival by deacetylating substrate proteins to drive the cell towards a cytoprotective pathway. Extreme stress conditions, however, can cause SIRT1 to lead cells down an apoptotic pathway instead. SIRT1 is frequently dysregulated in cancer cells and has been characterized to have a dual role as both an oncogene and a tumor suppressor, likely due to its pivotal function in regulating cytoprotection. Recently, the ability of SIRT1 to regulate HSF1-dependent induction of the heat shock response has highlighted another pathway through which SIRT1 can modulate cytoprotection. Activation of HSF1 results in the production of cytoprotective chaperones that can facilitate the transformed phenotype of cancer cells. In this review, we discuss the stress-dependent regulation of SIRT1. We highlight the role of SIRT1 in stress management and cytoprotection and emphasize SIRT1-dependent activation of HSF1 as a potential mechanism for cancer promotion. PMID:24020008

Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis

PubMed Central

Castillo-Quan, Jorge Iván; Li, Li; Kinghorn, Kerri J.; Ivanov, Dobril K.; Tain, Luke S.; Slack, Cathy; Kerr, Fiona; Nespital, Tobias; Thornton, Janet; Hardy, John; Bjedov, Ivana; Partridge, Linda

2016-01-01

Summary The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life. The life-extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) and activation of the transcription factor nuclear factor erythroid 2-related factor (NRF-2). Combining genetic loss of the NRF-2 repressor Kelch-like ECH-associated protein 1 (Keap1) with lithium treatment revealed that high levels of NRF-2 activation conferred stress resistance, while low levels additionally promoted longevity. The discovery of GSK-3 as a therapeutic target for aging will likely lead to more effective treatments that can modulate mammalian aging and further improve health in later life. PMID:27068460

Of Malthus and Methuselah: does longevity treatment aggravate global catastrophic risks?

NASA Astrophysics Data System (ADS)

Jebari, Karim

2014-12-01

Global catastrophic risk is a term that refers to the risk of the occurrence of an event that kills at least millions of people across several continents. While it has been argued by a number of scholars that one major potential risk comes from technology, the obscure nature of future technologies makes it difficult to utilize traditional probabilistic risk for the meaningful study of these risks. This article describes an alternative approach and applies it to a research program that has attracted a considerable amount of resources recently: namely longevity research. The aim of this research is to delay or reverse the ageing process. This article argues that this research program is much more risky or less beneficial than its proponents argue. In particular, they tend to underestimate the concerns associated with the potentially drastic population growth that longevity treatment could cause. The ethical benefit often ascribed to longevity treatment is that such treatment would add more subjective life-years that are worth living. However, in light of contemporary environmental problems, such an increase of the human population might be reckless. Drastically reducing fertility to reduce risks associated with environmental stress would make the benefits of such technology much less compelling.

Understanding the Natural and Socioeconomic Factors behind Regional Longevity in Guangxi, China: Is the Centenarian Ratio a Good Enough Indicator for Assessing the Longevity Phenomenon?

PubMed

Deng, Qucheng; Wei, Yongping; Zhao, Yan; Han, Xuerong; Yin, Juan

2018-05-08

Despite a number of longevity indicators having been used in previous longevity studies, few studies have critically evaluated whether these indicators are suitable to assess the regional longevity level. In addition, an increasing number of studies have attempted to determine the influence of socioeconomic and natural factors on regional longevity, but only certain factors were considered. This study aims to bridge this gap by determining the relationship between the 7 longevity indicators and selecting 24 natural and socioeconomic indicators in 109 selected counties and urban districts in Guangxi, China. This study has applied spatial analysis and geographically weighted regression as the main research methods. The seven longevity indicators here refer to centenarian ratio, longevity index, longevity level, aging tendency, 80⁺ ratio, 90⁺ ratio, and 95⁺ ratio. Natural indicators in this study mainly refer to atmospheric pressure, temperature, difference in temperature, humidity, rainfall, radiation, water vapor, and altitude. Socioeconomic indicators can be categorized into those related to economic status, education, local infrastructure, and health care facilities. The results show that natural factors such as the difference in temperature and altitude, along with socioeconomic factors such as GDP, might be the most significant contributors to the longevity of people aged 60⁻90 years in Guangxi. The longevity index and longevity level are useful supplementary indexes to the centenarian ratio for assessing the regional longevity.

Malathion-induced oxidative stress in a parasitoid wasp: effect on adult emergence, longevity, fecundity, and oxidative and antioxidative response of Pimpla turionellae (Hymenoptera: Ichneumonidae).

PubMed

Büyükgüzel, Kemal

2006-08-01

Effects of an organophosphorus insecticide, malathion, on survivorship and lipid peroxidation of the greater wax moth, Galleria mellonella (L.), pupae were investigated by rearing the newly hatched larvae on an artificial diet containing 0.01, 0.1, 1, 10, and 100 ppm of the insecticide. As bioindicators of long-term physiological stress responses, the adult emergence rate, longevity, and fecundity associated with lipid peroxidation level and antioxidant enzyme activity in the endoparasitoid Pimpla turionellae (L.) (Hymenoptera: Ichneumonidae) were determined by rearing the parasitoid on a factitious host, G. mellonella pupae treated with malathion. At 100 ppm, malathion significantly decreased pupation rate of G. mellonella larvae and the rate of adult emergence of the parasitoid from these pupae. This concentration resulted in a significant increase in the lipid peroxidation product malondialdehyde (MDA) in both the host and the parasitoid. Malathion at 1 and 10 ppm significantly increased pupation rate and lipid peroxidation level of G. mellonella pupae. The adult emergence rate of P. turionellae was significantly decreased from 63.7 to 20% by these concentrations, whereas MDA content was increased by two- and three-fold, respectively, compared with the control (45.3 +/- 3.2 nmol/ g protein). The longevity of adults was significantly extended from 52.5 +/- 5.7 to 75.7 +/- 6.3 d when the parasitoids emerged from host pupae exposed with 0.1 ppm malathion. At low concentrations (0.01 and 0.1 ppm), malathion significantly increased the number of eggs laid per female per day. However, the lowest concentration (0.01 ppm) had no significant effect on hatchability, whereas 0.1 ppm of the insecticide resulted in significant decrease in egg hatch compared with the control. A significant increase in total superoxide dismutase (SOD) activity for low concentrations of malathion (0.01-1 ppm) was found compared with the control. There was a significant positive correlation of

Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population

PubMed Central

Yan, Dongjing; Liao, Xiaoping; Wang, Xianshou; Fu, Yunxin; Cai, Wangwei

2016-01-01

Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found. However, when stratifying by gender, four SNPs (rs10499051, rs7762395, rs4946933 and rs3800230) previously reported to be associated with longevity and one novel SNP (rs4945815) showed significant association with male longevity (P-values: 0.007–0.032), but all SNPs were not associated with female longevity. Correspondingly, males carrying the G-G-T-G haplotype of rs10499051, rs7762395, rs4945815 and rs3800230 tended to have longer lifespan than those carrying the most common haplotype A-G-C-T (odds ratio = 2.36, 95% confidence interval = 1.20–4.63, P = 0.013). However, none of the associated SNPs and haplotype remained significant after Bonferroni correction. In conclusion, our findings revealed that the FOXO3 variants we tested in our population of Chinese men and women were associated with longevity in men only. None of these associations passed Bonferroni correction. Bonferroni correction is very stringent for association studies. We therefore believe the effects of these nominally significant variants on human longevity will be confirmed by future studies. PMID:27936216

Protein Repair l-Isoaspartyl Methyltransferase1 Is Involved in Both Seed Longevity and Germination Vigor in Arabidopsis[W

PubMed Central

Ogé, Laurent; Bourdais, Gildas; Bove, Jérôme; Collet, Boris; Godin, Béatrice; Granier, Fabienne; Boutin, Jean-Pierre; Job, Dominique; Jullien, Marc; Grappin, Philippe

2008-01-01

The formation of abnormal amino acid residues is a major source of spontaneous age-related protein damage in cells. The protein l-isoaspartyl methyltransferase (PIMT) combats protein misfolding resulting from l-isoaspartyl formation by catalyzing the conversion of abnormal l-isoaspartyl residues to their normal l-aspartyl forms. In this way, the PIMT repair enzyme system contributes to longevity and survival in bacterial and animal kingdoms. Despite the discovery of PIMT activity in plants two decades ago, the role of this enzyme during plant stress adaptation and in seed longevity remains undefined. In this work, we have isolated Arabidopsis thaliana lines exhibiting altered expression of PIMT1, one of the two genes encoding the PIMT enzyme in Arabidopsis. PIMT1 overaccumulation reduced the accumulation of l-isoaspartyl residues in seed proteins and increased both seed longevity and germination vigor. Conversely, reduced PIMT1 accumulation was associated with an increase in the accumulation of l-isoaspartyl residues in the proteome of freshly harvested dry mature seeds, thus leading to heightened sensitivity to aging treatments and loss of seed vigor under stressful germination conditions. These data implicate PIMT1 as a major endogenous factor that limits abnormal l-isoaspartyl accumulation in seed proteins, thereby improving seed traits such as longevity and vigor. The PIMT repair pathway likely works in concert with other anti-aging pathways to actively eliminate deleterious protein products, thus enabling successful seedling establishment and strengthening plant proliferation in natural environments. PMID:19011119

Genetics of healthy aging and longevity.

PubMed

Brooks-Wilson, Angela R

2013-12-01

Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and

Sex differences in cognitive regulation of psychosocial achievement stress: brain and behavior.

PubMed

Kogler, Lydia; Gur, Ruben C; Derntl, Birgit

2015-03-01

Although cognitive regulation of emotion has been extensively examined, there is a lack of studies assessing cognitive regulation in stressful achievement situations. This study used functional magnetic resonance imaging in 23 females and 20 males to investigate cognitive downregulation of negative, stressful sensations during a frequently used psychosocial stress task. Additionally, subjective responses, cognitive regulation strategies, salivary cortisol, and skin conductance response were assessed. Subjective response supported the experimental manipulation by showing higher anger and negative affect ratings after stress regulation than after the mere exposure to stress. On a neural level, right middle frontal gyrus (MFG) and right superior temporal gyrus (STG) were more strongly activated during regulation than nonregulation, whereas the hippocampus was less activated during regulation. Sex differences were evident: after regulation females expressed higher subjective stress ratings than males, and these ratings were associated with right hippocampal activation. In the nonregulation block, females showed greater activation of the left amygdala and the right STG during stress than males while males recruited the putamen more robustly in this condition. Thus, cognitive regulation of stressful achievement situations seems to induce additional stress, to recruit regions implicated in attention integration and working memory and to deactivate memory retrieval. Stress itself is associated with greater activation of limbic as well as attention areas in females than males. Additionally, activation of the memory system during cognitive regulation of stress is associated with greater perceived stress in females. Sex differences in cognitive regulation strategies merit further investigation that can guide sex sensitive interventions for stress-associated disorders. © 2014 Wiley Periodicals, Inc.

The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity

PubMed Central

Li, Yuan; Chen, Baohui; Zou, Wei; Wang, Xin; Wu, Yanwei; Zhao, Dongfeng; Sun, Yanan; Liu, Yubing

2016-01-01

Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16–dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity. PMID:27810910

Understanding the natural and social factors behind regional longevity in Guangxi, China—Is centenarian ratio a good enough indicator for assessing the longevity level?

NASA Astrophysics Data System (ADS)

Deng, Q.; Wei, Y.; Zhao, Y.

2017-12-01

Despite a number of longevity indicators having been used in previous longevity studies, few studies have critically evaluated whether these indicators are suitable. In addition, an increasing number of studies have attempted to determine the influence of socio-economic and natural factors on regional longevity, but only certain factors were considered. The present study bridges this gap by determining the relationship between the seven longevity indicators and selecting 24 natural and socio-economic indicators in the 91 selected counties and districts in Guangxi, China. The seven longevity indicators here refer to Centenarian ratio, Longevity index, Longevity level, Aging tendency, 80+ ratio, 90+ ratio and 95+ ratio. Natural indicators in this study mainly refer to climatic ones. Socio-economic indicators can be categorized into those related to economic, education, local infrastructure, and health care facilities. These data were mainly drawn from the Meteorological Data Sharing Service System and Guangxi's sixth population census. Stepwise regression analysis has been used as the primary research method to determine the relationship between the longevity indicators and the natural, social, and economic indicators. The results show that the climate factors regarding atmospheric pressure, humidity, and rainfall are the most significant contributors to the longevity of the 60- to 90-year-old elderly in Guangxi, while the difference of mean annual temperature could have negative impacts. Also, the natural and socioeconomic factors that impact the extremely old population (those over 95 years old) in Guangxi are still not clear. This study reveals that the longevity index and longevity level are useful supplementary indexes to the centenarian ratio for assessing the regional longevity as they could help reflect the regional longevity regarding the proportion of young-old and old-old population and not just limit to those over 100 years old. The elderly (those from 60

Association between Longevity and Element Levels in Food and Drinking Water of Typical Chinese Longevity Area.

PubMed

Hao, Z; Liu, Y; Li, Y; Song, W; Yu, J; Li, H; Wang, W

2016-01-01

To carrying out an integrated analysis on regional environment and human health in China and to detect the association between longevity and daily element intake from food and drinking water. Cross-sectional study. All the 18 cities and counties in Hainan Province. The distribution of elderly population and longevity indexes at a county level in Hainan Province were investigated. Quality of food and drinking water in Hainan was evaluated by comparing the chemical elements with National Standards. In addition, the association between element concentrations in food and water and longevity was examined using spearman's rank correlation. The proportion of elderly people is higher in the northern part of the province compared with southern counties. Food contributes a greater proportion of daily element intake than drinking water. Compared with the National Standards, reaching rates for elements were over 85% for both food and drinking water. There was a positive correlation between daily intake of Cu, Se, and Zn from food and water and aging and longevity indexes, and a negative correlation between Pb intake and these indexes. The quality of food and water in Hainan Province are good and that, compared with water, food is a more important source of trace elements. An appropriate supply of Cu, Se, and Zn is important, whereas excessive intake of Pb should be avoided. The findings also provide basic data to support further studies on regional variations in longevity and their relationship to diet and drinking water.

Typologies of Extreme Longevity Myths

PubMed Central

Young, Robert D.; Desjardins, Bertrand; McLaughlin, Kirsten; Poulain, Michel; Perls, Thomas T.

2010-01-01

Purpose. Political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. We describe various causes of false claims of extraordinary longevity. Design and Methods. American Social Security Death Index files for the period 1980–2009 were queried for individuals with birth and death dates yielding ages 110+ years of age. Frequency was compared to a list of age-validated supercentenarians maintained by the Gerontology Research Group who died during the same time period. Age claims of 110+ years and the age validation experiences of the authors facilitated a list of typologies of false age claims. Results. Invalid age claim rates increase with age from 65% at age 110-111 to 98% by age 115 to 100% for 120+ years. Eleven typologies of false claims were: Religious Authority Myth, Village Elder Myth, Fountain of Youth Myth (substance), Shangri-La Myth (geographic), Nationalist Pride, Spiritual Practice, Familial Longevity, Individual and/or Family Notoriety, Military Service, Administrative Entry Error, and Pension-Social Entitlement Fraud. Conclusions. Understanding various causes of false extreme age claims is important for placing current, past, and future extreme longevity claims in context and for providing a necessary level of skepticism. PMID:21461047

Typologies of extreme longevity myths.

PubMed

Young, Robert D; Desjardins, Bertrand; McLaughlin, Kirsten; Poulain, Michel; Perls, Thomas T

2010-01-01

Purpose. Political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. We describe various causes of false claims of extraordinary longevity. Design and Methods. American Social Security Death Index files for the period 1980-2009 were queried for individuals with birth and death dates yielding ages 110+ years of age. Frequency was compared to a list of age-validated supercentenarians maintained by the Gerontology Research Group who died during the same time period. Age claims of 110+ years and the age validation experiences of the authors facilitated a list of typologies of false age claims. Results. Invalid age claim rates increase with age from 65% at age 110-111 to 98% by age 115 to 100% for 120+ years. Eleven typologies of false claims were: Religious Authority Myth, Village Elder Myth, Fountain of Youth Myth (substance), Shangri-La Myth (geographic), Nationalist Pride, Spiritual Practice, Familial Longevity, Individual and/or Family Notoriety, Military Service, Administrative Entry Error, and Pension-Social Entitlement Fraud. Conclusions. Understanding various causes of false extreme age claims is important for placing current, past, and future extreme longevity claims in context and for providing a necessary level of skepticism.

Viability, Longevity, and Egg Production of Drosophila melanogaster Are Regulated by the miR-282 microRNA

PubMed Central

Vilmos, Péter; Bujna, Ágnes; Szuperák, Milán; Havelda, Zoltán; Várallyay, Éva; Szabad, János; Kucerova, Lucie; Somogyi, Kálmán; Kristó, Ildikó; Lukácsovich, Tamás; Jankovics, Ferenc; Henn, László; Erdélyi, Miklós

2013-01-01

The first microRNAs were discovered some 20 years ago, but only a small fraction of the microRNA-encoding genes have been described in detail yet. Here we report the molecular analysis of a computationally predicted Drosophila melanogaster microRNA gene, mir-282. We show that the mir-282 gene is the source of a 4.9-kb-long primary transcript with a 5′ cap and a 3′-poly(A) sequence and a mature microRNA of ∼25 bp. Our data strongly suggest the existence of an independent mir-282 gene conserved in holometabolic insects. We give evidence that the mir-282 locus encodes a functional transcript that influences viability, longevity, and egg production in Drosophila. We identify the nervous system-specific adenylate cyclase (rutabaga) as a target of miR-282 and assume that one of the main functions of mir-282 is the regulation of adenylate cyclase activity in the nervous system during metamorphosis. PMID:23852386

Autonomous orientation predicts longevity: New findings from the Nun Study.

PubMed

Weinstein, Netta; Legate, Nicole; Ryan, William S; Hemmy, Laura

2018-03-10

Work on longevity has found protective social, cognitive, and emotional factors, but to date we have little understanding of the impact of motivational dynamics. Autonomy orientation, or stable patterns of self-regulation, is theorized to be a protective factor for long-term mental and physical health (Ryan & Deci, 2017), and it is therefore a prime candidate for examining how stable psychosocial factors are linked to longevity, or life expectancy. Essays written in the 1930s by participants in the Nun Study were coded for indicators of an autonomy orientation. These were selected in line with an extensive theoretical literature based in self-determination theory (Deci & Ryan, 1985). Essays were coded for the propensity for choice in action, susceptibility to pressure, self-reflection, integration of experiences, and parental support for autonomy. These coded variables were used to predict age of death. Using 176 codable essays provided by now-deceased participants, linear regression analyses revealed that choiceful behavior, self-reflection, and parent autonomy support predicted age of death. Participants who demonstrated these stable and beneficial motivational characteristics lived longer. Personality constructs reflecting a healthy form of self-regulation are associated with long-term health. Implications for health interventions are discussed. © 2018 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans.

PubMed

Hahm, Jeong-Hoon; Kim, Sunhee; Paik, Young-Ki

2009-08-01

G-proteins, including GPA-3, play an important role in regulating physiological responses in Caenorhabditis elegans. When confronted with an environmental stimulus such as dauer pheromone, or poor nutrients, C. elegans receives and integrates external signals through its nervous system (i.e. amphid neurons), which interprets and translates them into biological action. Here it is shown that a suppressed neuronal cGMP level caused by GPA-3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans through forkhead transcription factor family O (FOXO)-mediated signal. A reduced neuronal cGMP level was found to be caused by an increased cGMP-specific phosphodiesterase activity at the transcriptional level. Our results using C. elegans mutants with specific deficits in TGF-beta and FOXO RNAi system suggest a mechanism in that cGMP, TGF-beta, and FOXO signaling interact to differentially produce the insulin-like molecules, ins-7 and daf-28, causing suppression of the insulin/IGF-1 pathway and promoting lifespan extension. Our findings provide not only a new mechanism of cGMP-mediated induction of longevity in adult C. elegans but also a possible therapeutic strategy for neuronal disease, which has been likened to brain diabetes.

ATF5 regulates β-cell survival during stress.

PubMed

Juliana, Christine A; Yang, Juxiang; Rozo, Andrea V; Good, Austin; Groff, David N; Wang, Shu-Zong; Green, Michael R; Stoffers, Doris A

2017-02-07

The stress response and cell survival are necessary for normal pancreatic β-cell function, glucose homeostasis, and prevention of diabetes. The homeodomain transcription factor and human diabetes gene pancreas/duodenum homeobox protein 1 (Pdx1) regulates β-cell survival and endoplasmic reticulum stress susceptibility, in part through direct regulation of activating transcription factor 4 (Atf4). Here we show that Atf5, a close but less-studied relative of Atf4, is also a target of Pdx1 and is critical for β-cell survival under stress conditions. Pdx1 deficiency led to decreased Atf5 transcript, and primary islet ChIP-sequencing localized PDX1 to the Atf5 promoter, implicating Atf5 as a PDX1 target. Atf5 expression was stress inducible and enriched in β cells. Importantly, Atf5 deficiency decreased survival under stress conditions. Loss-of-function and chromatin occupancy experiments positioned Atf5 downstream of and parallel to Atf4 in the regulation of eIF4E-binding protein 1 (4ebp1), a mammalian target of rapamycin (mTOR) pathway component that inhibits protein translation. Accordingly, Atf5 deficiency attenuated stress suppression of global translation, likely enhancing the susceptibility of β cells to stress-induced apoptosis. Thus, we identify ATF5 as a member of the transcriptional network governing pancreatic β-cell survival during stress.

ATF5 regulates β-cell survival during stress

PubMed Central

Juliana, Christine A.; Yang, Juxiang; Rozo, Andrea V.; Good, Austin; Groff, David N.; Wang, Shu-Zong; Stoffers, Doris A.

2017-01-01

The stress response and cell survival are necessary for normal pancreatic β-cell function, glucose homeostasis, and prevention of diabetes. The homeodomain transcription factor and human diabetes gene pancreas/duodenum homeobox protein 1 (Pdx1) regulates β-cell survival and endoplasmic reticulum stress susceptibility, in part through direct regulation of activating transcription factor 4 (Atf4). Here we show that Atf5, a close but less-studied relative of Atf4, is also a target of Pdx1 and is critical for β-cell survival under stress conditions. Pdx1 deficiency led to decreased Atf5 transcript, and primary islet ChIP-sequencing localized PDX1 to the Atf5 promoter, implicating Atf5 as a PDX1 target. Atf5 expression was stress inducible and enriched in β cells. Importantly, Atf5 deficiency decreased survival under stress conditions. Loss-of-function and chromatin occupancy experiments positioned Atf5 downstream of and parallel to Atf4 in the regulation of eIF4E-binding protein 1 (4ebp1), a mammalian target of rapamycin (mTOR) pathway component that inhibits protein translation. Accordingly, Atf5 deficiency attenuated stress suppression of global translation, likely enhancing the susceptibility of β cells to stress-induced apoptosis. Thus, we identify ATF5 as a member of the transcriptional network governing pancreatic β-cell survival during stress. PMID:28115692

The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

PubMed Central

Solon-Biet, Samantha M.; McMahon, Aisling C.; Ballard, J. William O.; Ruohonen, Kari; Wu, Lindsay E.; Cogger, Victoria C.; Warren, Alessandra; Huang, Xin; Pichaud, Nicolas; Melvin, Richard G.; Gokarn, Rahul; Khalil, Mamdouh; Turner, Nigel; Cooney, Gregory J.; Sinclair, David A.; Raubenheimer, David; Le Couteur, David G.; Simpson, Stephen J.

2016-01-01

Summary The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation. PMID:24606899

Mutation of C. elegans demethylase spr-5 extends transgenerational longevity

PubMed Central

Greer, Eric Lieberman; Becker, Ben; Latza, Christian; Antebi, Adam; Shi, Yang

2016-01-01

Complex organismal properties such as longevity can be transmitted across generations by non-genetic factors. Here we demonstrate that deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase, spr-5, causes a trans-generational increase in lifespan. We identify a chromatin-modifying network, which regulates this lifespan extension. We further show that this trans-generational lifespan extension is dependent on a hormonal signaling pathway involving the steroid dafachronic acid, an activator of the nuclear receptor DAF-12. These findings suggest that loss of the demethylase SPR-5 causes H3K4me2 mis-regulation and activation of a known lifespan-regulating signaling pathway, leading to trans-generational lifespan extension. PMID:26691751

When stress predicts a shrinking gene pool, trading early reproduction for longevity can increase fitness, even with lower fecundity.

PubMed

Ratcliff, William C; Hawthorne, Peter; Travisano, Michael; Denison, R Ford

2009-06-25

Stresses like dietary restriction or various toxins increase lifespan in taxa as diverse as yeast, Caenorhabditis elegans, Drosophila and rats, by triggering physiological responses that also tend to delay reproduction. Food odors can reverse the effects of dietary restriction, showing that key mechanisms respond to information, not just resources. Such environmental cues can predict population trends, not just individual prospects for survival and reproduction. When population size is increasing, each offspring produced earlier makes a larger proportional contribution to the gene pool, but the reverse is true when population size is declining. We show mathematically that natural selection can favor facultative delay in reproduction when environmental cues predict a decrease in total population size, even if lifetime fecundity decreases with delay. We also show that increased reproduction from waiting for better conditions does not increase fitness (proportional representation) when the whole population benefits similarly. We conclude that the beneficial effects of stress on longevity (hormesis) in diverse taxa are a side-effect of delaying reproduction in response to environmental cues that population size is likely to decrease. The reversal by food odors of the effects of dietary restriction can be explained as a response to information that population size is less likely to decrease, reducing the chance that delaying reproduction will increase fitness.

A Method to Find Longevity-Selected Positions in the Mammalian Proteome

PubMed Central

Semeiks, Jeremy; Grishin, Nick V.

2012-01-01

Evolutionary theory suggests that the force of natural selection decreases with age. To explore the extent to which this prediction directly affects protein structure and function, we used multiple regression to find longevity-selected positions, defined as the columns of a sequence alignment conserved in long-lived but not short-lived mammal species. We analyzed 7,590 orthologous protein families in 33 mammalian species, accounting for body mass, phylogeny, and species-specific mutation rate. Overall, we found that the number of longevity-selected positions in the mammalian proteome is much higher than would be expected by chance. Further, these positions are enriched in domains of several proteins that interact with one another in inflammation and other aging-related processes, as well as in organismal development. We present as an example the kinase domain of anti-Müllerian hormone type-2 receptor (AMHR2). AMHR2 inhibits ovarian follicle recruitment and growth, and a homology model of the kinase domain shows that its longevity-selected positions cluster near a SNP associated with delayed human menopause. Distinct from its canonical role in development, this region of AMHR2 may function to regulate the protein’s activity in a lifespan-specific manner. PMID:22701678

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

PubMed

Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; McMackin, Marissa Z; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

2017-09-05

Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-Regulation and Economic Stress in Children of Hispanic Immigrants and Their Peers: Better Regulation at a Cost?

PubMed Central

McFadyen-Ketchum, Lisa Schlueter; Hurwich-Reiss, Eliana; Stiles, Allison A.; Mendoza, Marina M.; Badanes, Lisa S.; Dmitrieva, Julia; Watamura, Sarah Enos

2017-01-01

Research Findings Although there is a well-established relationship between economic stress and children’s self-regulation, few studies have examined this relationship in children of Hispanic immigrants (COHIs), a rapidly growing population. In a sample of preschool children (N = 165), we examined whether economic stress predicted teacher evaluations of children’s self-regulation, whether economic stress predicted children’s physiological reactivity (via cortisol levels), and whether economic stress had a similar effect on self-regulation and children’s cortisol for COHI versus nonimmigrant children. Greater economic stress was associated with poorer child self-regulation and heightened physiological reactivity across a challenging classroom task for the sample as a whole. However, when we examined children by group, greater economic stress was associated with poorer teacher-reported self-regulation for nonimmigrant children only. In contrast, greater economic stress was related to greater cortisol reactivity across a challenge task for COHIs but not for nonimmigrants. Practice or Policy Results demonstrate the importance of considering physiological indices of self-regulation (heightened stress physiology), in addition to traditional external indices (teacher report), when assessing self-regulation or risk more generally among preschool samples that are diverse in terms of ethnicity, economic risk, and parents’ nativity. PMID:28943740

The rate of metabolism as a factor determining longevity of the Saccharomyces cerevisiae yeast.

PubMed

Molon, Mateusz; Szajwaj, Monika; Tchorzewski, Marek; Skoczowski, Andrzej; Niewiadomska, Ewa; Zadrag-Tecza, Renata

2016-02-01

Despite many controversies, the yeast Saccharomyces cerevisiae continues to be used as a model organism for the study of aging. Numerous theories and hypotheses have been created for several decades, yet basic mechanisms of aging have remained unclear. Therefore, the principal aim of this work is to propose a possible mechanism leading to increased longevity in yeast. In this paper, we suggest for the first time that there is a link between decreased metabolic activity, fertility and longevity expressed as time of life in yeast. Determination of reproductive potential and total lifespan with the use of fob1Δ and sfp1Δ mutants allows us to compare the "longevity" presented as the number of produced daughters with the longevity expressed as the time of life. The results of analyses presented in this paper suggest the need for a change in the definition of longevity of yeast by taking into consideration the time parameter. The mutants that have been described as "long-lived" in the literature, such as the fob1Δ mutant, have an increased reproductive potential but live no longer than their standard counterparts. On the other hand, the sfp1Δ mutant and the wild-type strain produce a similar number of daughter cells, but the former lives much longer. Our results demonstrate a correlation between the decreased efficiency of the translational apparatus and the longevity of the sfp1Δ mutant. We suggest that a possible factor regulating the lifespan is the rate of cell metabolism. To measure the basic metabolism of the yeast cells, we used the isothermal microcalorimetry method. In the case of sfp1Δ, the flow of energy, ATP concentration, polysome profile and translational fitness are significantly lower in comparison with the wild-type strain and the fob1Δ mutant.

HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1.

PubMed

Shamalnasab, Mehrnaz; Dhaoui, Manel; Thondamal, Manjunatha; Harvald, Eva Bang; Færgeman, Nils J; Aguilaniu, Hugo; Fabrizio, Paola

2017-07-27

In yeast, the broadly conserved acyl-CoA-binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene expression studies we have demonstrated that HIF-1, a master transcriptional regulator of adaptation to hypoxia, plays a central role in orchestrating the anti-aging response induced by MAA-1 deficiency. This response relies on the activation of molecular chaperones known to contribute to maintenance of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1 -deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins in the age-associated decline in proteostasis in mammals.

Masculine Discrepancy Stress, Emotion-Regulation Difficulties, and Intimate Partner Violence

PubMed Central

Berke, Danielle S.; Reidy, Dennis E.; Gentile, Brittany; Zeichner, Amos

2018-01-01

Research suggests that masculine socialization processes contribute to the perpetration of intimate partner violence (IPV) by men. Although this research has traditionally focused on men who strongly adhere to traditional gender norms, men who negatively evaluate themselves as falling short of these norms (a construct termed masculine discrepancy stress) have proven to be at increased risk of IPV perpetration. Likewise, men experiencing problems with emotion regulation, a multidimensional construct reflecting difficulties in effectively experiencing and responding to emotional states, are also at risk of IPV perpetration. In the present research, we tested the hypothesis that the link between discrepancy stress and IPV perpetration is mediated via difficulties in emotion regulation. Three hundred fifty-seven men completed online surveys assessing their experience of discrepancy stress, emotion-regulation difficulties, and history of IPV perpetration. Results indicated that discrepancy-stressed men's use of physical IPV was fully mediated by emotion-regulation difficulties. In addition, emotion-regulation difficulties partially mediated the association between discrepancy stress and sexual IPV. Findings are discussed in terms of the potential utility of emotion-focused interventions for modifying men's experience and expression of discrepancy stress and reducing perpetration of IPV. PMID:27226013

Masculine Discrepancy Stress, Emotion-Regulation Difficulties, and Intimate Partner Violence.

PubMed

Berke, Danielle S; Reidy, Dennis E; Gentile, Brittany; Zeichner, Amos

2016-05-24

Research suggests that masculine socialization processes contribute to the perpetration of intimate partner violence (IPV) by men. Although this research has traditionally focused on men who strongly adhere to traditional gender norms, men who negatively evaluate themselves as falling short of these norms (a construct termed masculine discrepancy stress) have proven to be at increased risk of IPV perpetration. Likewise, men experiencing problems with emotion regulation, a multidimensional construct reflecting difficulties in effectively experiencing and responding to emotional states, are also at risk of IPV perpetration. In the present research, we tested the hypothesis that the link between discrepancy stress and IPV perpetration is mediated via difficulties in emotion regulation. Three hundred fifty-seven men completed online surveys assessing their experience of discrepancy stress, emotion-regulation difficulties, and history of IPV perpetration. Results indicated that discrepancy-stressed men's use of physical IPV was fully mediated by emotion-regulation difficulties. In addition, emotion-regulation difficulties partially mediated the association between discrepancy stress and sexual IPV. Findings are discussed in terms of the potential utility of emotion-focused interventions for modifying men's experience and expression of discrepancy stress and reducing perpetration of IPV. © The Author(s) 2016.

The crucial impact of lysosomes in aging and longevity.

PubMed

Carmona-Gutierrez, Didac; Hughes, Adam L; Madeo, Frank; Ruckenstuhl, Christoph

2016-12-01

Lysosomes are the main catabolic organelles of a cell and play a pivotal role in a plethora of cellular processes, including responses to nutrient availability and composition, stress resistance, programmed cell death, plasma membrane repair, development, and cell differentiation. In line with this pleiotropic importance for cellular and organismal life and death, lysosomal dysfunction is associated with many age-related pathologies like Parkinson's and Alzheimer's disease, as well as with a decline in lifespan. Conversely, targeting lysosomal functional capacity is emerging as a means to promote longevity. Here, we analyze the current knowledge on the prominent influence of lysosomes on aging-related processes, such as their executory and regulatory roles during general and selective macroautophagy, or their storage capacity for amino acids and ions. In addition, we review and discuss the roles of lysosomes as active players in the mechanisms underlying known lifespan-extending interventions like, for example, spermidine or rapamycin administration. In conclusion, this review aims at critically examining the nature and pliability of the different layers, in which lysosomes are involved as a control hub for aging and longevity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Reproduction alters oxidative status when it is traded-off against longevity.

PubMed

Beaulieu, Michaël; Geiger, Rina E; Reim, Elisabeth; Zielke, Luisa; Fischer, Klaus

2015-07-01

Oxidative stress has been proposed to mediate one of the most important aspects of life-history evolution: the trade-off between reproduction and self-maintenance. However, empirical studies have cast doubt on the generality of this intriguing notion. Here, we hypothesize that reproduction alters oxidative status only when a trade-off between reproduction and self-maintenance occurs. Accordingly, in female Bicyclus anynana butterflies, we found that reproduction affected oxidative markers only under challenging thermal conditions that made the trade-off between reproduction and longevity emerge. Interestingly, under such conditions, butterflies favored longevity over reproduction, suggesting that self-maintenance mechanisms were activated. Accordingly, butterflies reproducing under challenging thermal conditions exhibited enhanced antioxidant defenses and stable oxidative damage. Altogether, our results indicate that a trade-off between reproduction and self-maintenance is indeed a necessary condition for reproduction to alter oxidative status, and that the effects of such a trade-off on oxidative status depend on whether priority is given to self-maintenance or reproduction. Assessing the existence of the trade-off between self-maintenance and reproduction, and whether self-maintenance is prioritized relative to reproduction is therefore crucial for understanding variation in oxidative status in reproducing animals, which may clarify the general implication of oxidative stress in the resolution of life-history trade-offs. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Comparison of biochemical data, blood pressure and physical activity between longevity and non-longevity districts in Japan.

PubMed

Mori, Ichiro; Ishizuka, Tatsuo; Morita, Hiroyuki; Matsumoto, Masami; Uno, Yoshihiro; Kajita, Kazuo; Ikeda, Takahide; Fujioka, Kei; Matsubara, Kenji

2008-10-01

There is controversy about longevity-associated factors, including environmental and genetic factors. Clinical and epidemiological studies suggest that multiple risk factors decrease life-span, but there has not been a definitive report regarding the association of risk factors with longevity. The ultimate aim of the present study was to prevent the overwhelming increase in life-style-related diseases by evaluating this association in 2 districts in Japan. Plasma glucose levels, hemoglobin (Hb) A1c, lipids, dehydroepiandrosterone-sulfate, adiponectin and physical activity were examined in 133 subjects (M/F 47/86, 67+/-1 years) in Kokufu, a longevity district (mean life span: 80.4 years according to 2000 Japanese census) and 69 subjects (M/F 29/40, 62+/-1 years) in Miyama, a non-longevity district (mean life span 77.4 years, 2000 census). There were significant differences in systolic and diastolic blood pressures (BPs, p < 0.001), exercise capacity (p < 0.0001) and plasma adiponectin levels (p < 0.04) between the districts. Plasma adiponectin level was significantly correlated with high-density lipoprotein-cholesterol (HDL-C) (r = 0.333, p < 0.0001), triglyceride (TG) (r = -0.161, p < 0.04), HbA1c (r = -0.163, p < 0.03) and HOMA-R (r = -0.163, p < 0.03). Life-style-related factors such as BP, exercise capacity and plasma adiponectin levels might play an important role in longevity, and those of HDL-C and TG, as well as glucose tolerance, might be associated with adiponectin levels.

Longevity and aging. Mechanisms and perspectives.

PubMed

Labat-Robert, J; Robert, L

2015-12-01

Longevity can mostly be determined with relative accuracy from birth and death registers when available. Aging is a multifactorial process, much more difficult to quantitate. Every measurable physiological function declines with specific speeds over a wide range. The mechanisms involved are also different, genetic factors are of importance for longevity determinations. The best-known genes involved are the Sirtuins, active at the genetic and epigenetic level. Aging is multifactorial, not "coded" in the genome. There are, however, a number of well-studied physical and biological parameters involved in aging, which can be determined and quantitated. We shall try to identify parameters affecting longevity as well as aging and suggest some reasonable predictions for the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Longevity health sciences and mental health as future medicine.

PubMed

Riga, Sorin; Riga, Dan; Mihailescu, Alexandra; Motoc, Daniela; Mos, Liana; Schneider, Francisc

2010-06-01

Longevity health sciences and mental health are fields of public health and of preventive and integrative medicine. The antagonism between health construction and human pathology is substantiated by two opposite fundamental pathways: the health-longevity tetrad versus the aging-disease cascade. It is necessary that the current paradigm of contemporary medicine be replaced by the advanced paradigm of future medicine. A societal cost-benefit rate is decisive for health-longevity promotion. This is why the WHO public health strategy keeps forwarding the societal medical target into the global health-longevity field.

Behavioral Assessment of Spaceflight Effects on Neurocognitive Performance - Extent and Longevity

NASA Technical Reports Server (NTRS)

De Dios, Y.E.; Kofman, I.S.; Gadd, N.E.; Kreutzberg, G.A.; Peters, B.T.; Taylor, L.C.; Campbell, D.J.; Wood, S.J.; Bloomberg, J.J.; Seidler, R.D.;

HIF-1–dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA–binding protein MAA-1

PubMed Central

Shamalnasab, Mehrnaz; Dhaoui, Manel; Thondamal, Manjunatha; Harvald, Eva Bang; Færgeman, Nils J.; Aguilaniu, Hugo; Fabrizio, Paola

2017-01-01

In yeast, the broadly conserved acyl-CoA–binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene expression studies we have demonstrated that HIF-1, a master transcriptional regulator of adaptation to hypoxia, plays a central role in orchestrating the anti-aging response induced by MAA-1 deficiency. This response relies on the activation of molecular chaperones known to contribute to maintenance of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1 –deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins in the age-associated decline in proteostasis in mammals. PMID:28758895

The Longevity Consortium: Harnessing diverse approaches to understand the genetic basis of human longevity and healthy aging. An introduction to a series of articles.

PubMed

Kahn, Arnold

2011-04-01

The Longevity Consortium is a multi-investigator, multi-institutional research group focused on identifying the genetic variants that regulate human lifespan and healthy aging. The text that follows is an introduction to a series of seven articles prepared by Consortium investigators that represent a profile of planned and ongoing research and up-to-date reviews of topics of major interest to biogerontologists and others scientists and clinicians interested in ageing research. Copyright © 2010 Elsevier B.V. All rights reserved.

77 FR 66566 - Stress Testing of Regulated Entities

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-06

... 2590-AA47 Stress Testing of Regulated Entities AGENCY: Federal Housing Finance Agency. ACTION: Notice... concerning stress testing of the Federal National Mortgage Association (Fannie Mae), the Federal Home Loan...

The DAF-16 FOXO Transcription Factor Regulates natc-1 to Modulate Stress Resistance in Caenorhabditis elegans, Linking Insulin/IGF-1 Signaling to Protein N-Terminal Acetylation

PubMed Central

Warnhoff, Kurt; Murphy, John T.; Kumar, Sandeep; Schneider, Daniel L.; Peterson, Michelle; Hsu, Simon; Guthrie, James; Robertson, J. David; Kornfeld, Kerry

2014-01-01

The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance. PMID:25330323

78 FR 59219 - Stress Testing of Regulated Entities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

... FEDERAL HOUSING FINANCE AGENCY 12 CFR Part 1238 RIN 2590-AA47 Stress Testing of Regulated Entities... assets of more than $10 billion to conduct annual stress tests to determine whether the companies have... federal financial regulatory agency, to conduct annual stress tests to determine whether the companies...

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

PubMed Central

Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

2017-01-01

Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients’ personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior – including suicide – and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD. PMID:29250007

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

PubMed

Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

2017-01-01

Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients' personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior - including suicide - and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD.

The significance of translation regulation in the stress response

PubMed Central

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although m

Regulating Anger under Stress via Cognitive Reappraisal and Sadness.

PubMed

Zhan, Jun; Wu, Xiaofei; Fan, Jin; Guo, Jianyou; Zhou, Jianshe; Ren, Jun; Liu, Chang; Luo, Jing

2017-01-01

Previous studies have reported the failure of cognitive emotion regulation (CER), especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC), but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film) could reduce aggressive behavior associated with anger [i.e., "sadness counteracts anger" (SCA)] (Zhan et al., 2015). Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants' subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one's ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER induction was found to

Regulating Anger under Stress via Cognitive Reappraisal and Sadness

PubMed Central

Zhan, Jun; Wu, Xiaofei; Fan, Jin; Guo, Jianyou; Zhou, Jianshe; Ren, Jun; Liu, Chang; Luo, Jing

2017-01-01

Previous studies have reported the failure of cognitive emotion regulation (CER), especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC), but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film) could reduce aggressive behavior associated with anger [i.e., “sadness counteracts anger” (SCA)] (Zhan et al., 2015). Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants’ subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one’s ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER induction was

Displacement behaviour regulates the experience of stress in men.

PubMed

Mohiyeddini, Changiz; Semple, Stuart

2013-03-01

Behavioural coping strategies represent a key means by which people regulate their stress levels. Attention has recently focused on the potential role in coping of 'displacement behaviour' - activities such as scratching, lip biting and face touching. Increased levels of displacement behaviour are associated with feelings of anxiety and stress; however, the extent to which displacement behaviour, as a short-term behavioural response to emotionally challenging stimuli, influences the subsequent experience of stress remains poorly understood. The aim of this study was to investigate the potential role of displacement behaviour in coping with stress. In a study population of 42 healthy adult men (mean age = 28.09 years, SD = 7.98), we quantified displacement behaviour during a Trier Social Stress Test (TSST), and used self-report questionnaires to assess trait and state anxiety before the TSST, and the experience of stress afterwards. We predicted displacement behaviour would diminish the negative impact of the stressful situation, and hence be associated with lower post-TSST stress levels. Furthermore, we predicted displacement behaviour would mediate the link between state and trait anxiety on the one hand and the experience of stress on the other. Results showed the rate of displacement behaviour was positively correlated with state anxiety but unrelated to trait anxiety, and negatively correlated with the self-reported experience of stress, in agreement with the idea that displacement behaviour has a crucial impact on regulation of stress. Moreover, serial mediation analyses using a bias-corrected bootstrapping approach indicated displacement behaviour mediated the relationship between state anxiety and the experience of stress, and that state anxiety and displacement behaviour - in combination, respectively - mediated the link between trait anxiety and experience of stress. These results shed important new light on the function of displacement behaviour, and

Mental Stress: Neurophysiology and Its Regulation by Sudarshan Kriya Yoga.

PubMed

Chandra, Sushil; Jaiswal, Amit Kumar; Singh, Ram; Jha, Devendra; Mittal, Alok Prakash

2017-01-01

The present study focuses on analyzing the effects of Sudarshan Kriya yoga (SKY) on EEG as well as ECG signals for stress regulation. To envision the regulation of stress Determination Test (DT) has been used. We have chosen a control group for contriving a cogent comparison that could be corroborated using statistical tests. A total of 20 subjects were taken in the study, of which 10 were allotted to a control group. Electroencephalograph was taken during a DT task, before and after SKY the sky session with 30 days of SKY session given to the experimental group. No SKY was given to the control group. We quantified mental stress using EEG, ECG and DT synergistically and used SKY to regulate it. We observed that alpha band power decreases in the frontal lobe of the brain with increasing mental stress while frontal brain asymmetry decreases with increasing stress tolerance. These EEG, ECG and DT shows a significant decrement in mental stress and improvement in cognitive performance after SKY, indicating SKY as a good alternative of medication for stress management.

Dietary and microbiome factors determine longevity in Caenorhabditis elegans

PubMed Central

Sánchez-Blanco, Adolfo; Rodríguez-Matellán, Alberto; González-Paramás, Ana; González-Manzano, Susana; Kim, Stuart K.; Mollinedo, Faustino

2016-01-01

Diet composition affects organismal health. Nutrient uptake depends on the microbiome. Caenorhabditis elegans fed a Bacillus subtilis diet live longer than those fed the standard Escherichia coli diet. Here we report that this longevity difference is primarily caused by dietary coQ, an antioxidant synthesized by E. coli but not by B. subtilis. CoQ-supplemented E. coli fed worms have a lower oxidation state yet live shorter than coQ-less B. subtilis fed worms. We showed that mutations affecting longevity for E. coli fed worms do not always lead to similar effects when worms are fed B. subtilis. We propose that coQ supplementation by the E. coli diet alters the worm cellular REDOX homeostasis, thus decreasing longevity. Our results highlight the importance of microbiome factors in longevity, argue that antioxidant supplementation can be detrimental, and suggest that the C. elegans standard E. coli diet can alter the effect of signaling pathways on longevity. PMID:27510225

The Role of Mammalian Sirtuins in the Regulation of Metabolism, Aging, and Longevity

PubMed Central

Satoh, Akiko; Stein, Liana

2013-01-01

Ever since the discovery of sirtuins a decade ago, interest in this family of NAD-dependent deacetylases has exploded, generating multiple lines of evidence implicating sirtuins as evolutionarily conserved regulators of lifespan. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Further investigation into the intimate connection among sirtuins, metabolism, and aging has implicated the activation of SIRT1 as both preventative and therapeutic measures against multiple age-associated disorders including type 2 diabetes and Alzheimer’s disease. SIRT1 activation has clear potential to not only prevent age-associated diseases but also to extend healthspan and perhaps lifespan. Sirtuin activating compounds and NAD intermediates are two promising ways to achieve these elusive goals. PMID:21879449

"Real life" longevity of implantable cardioverter-defibrillator devices.

PubMed

Manolis, Antonis S; Maounis, Themistoklis; Koulouris, Spyridon; Vassilikos, Vassilios

2017-09-01

Manufacturers of implantable cardioverter-defibrillators (ICDs) promise a 5- to 9-year projected longevity; however, real-life data indicate otherwise. The aim of the present study was to assess ICD longevity among 685 consecutive patients over the last 20 years. Real-life longevity of ICDs may differ from that stated by the manufacturers. The study included 601 men and 84 women (mean age, 63.1 ± 13.3 years). The underlying disease was coronary (n = 396) or valvular (n = 15) disease, cardiomyopathy (n = 220), or electrical disease (n = 54). The mean ejection fraction was 35%. Devices were implanted for secondary (n = 562) or primary (n = 123) prevention. Single- (n = 292) or dual-chamber (n = 269) or cardiac resynchronization therapy (CRT) devices (n = 124) were implanted in the abdomen (n = 17) or chest (n = 668). Over 20 years, ICD pulse generator replacements were performed in 238 patients (209 men; age 63.7 ± 13.9 years; ejection fraction, 37.7% ± 14.0%) who had an ICD for secondary (n = 210) or primary (n = 28) prevention. The mean ICD longevity was 58.3 ± 18.7 months. In 20 (8.4%) patients, devices exhibited premature battery depletion within 36 months. Most (94%) patients had none, minor, or modest use of ICD therapy. Longevity was longest for single-chamber devices and shortest for CRT devices. Latest-generation devices replaced over the second decade lasted longer compared with devices replaced during the first decade. When analyzed by manufacturer, Medtronic devices appeared to have longer longevity by 13 to 18 months. ICDs continue to have limited longevity of 4.9 ± 1.6 years, and 8% demonstrate premature battery depletion by 3 years. CRT devices have the shortest longevity (mean, 3.8 years) by 13 to 17 months, compared with other ICD devices. These findings have important implications, particularly in view of the high expense involved with this type of electrical

Isolation and identification of peanut leaf proteins regulated by water stress.

PubMed

Akkasaeng, Chutipong; Tantisuwichwong, Napaporn; Chairam, Issariya; Prakrongrak, Narumon; Jogloy, Sanun; Pathanothai, Aran

2007-05-15

Water deficits trigger signaling cascades leading to modulation of protein expression in plant tissues. Identification of peanut leaf proteins regulated by water stress provides some insights of cellular and molecular response of peanut plants to drought stress. Peanut variety Khon Kaen 4, a water-stress sensitive variety, was grown in a growth chamber under controlled environment. Water stress was imposed on day 30 after seedling emergence by withholding watering peanut plants for 6 days as compared to plants adequately supplied with water. Total protein were prepared from a leaflet of fully expanded leaf on the main stem. Proteins were separated in duplicated gels using two-dimensional gel electrophoresis and visualized by silver nitrate staining. Image analysis was performed using ImageMaster 2D Platinum 5.0 to determine proteins regulated by water stress. Molecular mass and isoelectric point of each regulated protein were used in database queries for protein identification. One protein was induced under water stress and the homologous protein was identified as Serine/threonine-protein phosphatase PP 1. Five proteins were down-regulated by water deficit. The homologous proteins were chaperone protein DNAJ, auxin-responsive protein IAA29, peroxidase 43, caffeoyl-CoA O-methyltransferase and SNF1-related protein kinase regulatory subunit beta-2. Down-regulated proteins may be associated with sensitivity of the peanut variety to water stress.

Dietary adenine controls adult lifespan via adenosine nucleotide biosynthesis and AMPK, and regulates the longevity benefit of caloric restriction

PubMed Central

Stenesen, Drew; Suh, Jae Myoung; Seo, Jin; Yu, Kweon; Lee, Kyu-Sun; Kim, Jong-Seok; Min, Kyung-Jin; Graff, Jonathan M.

2012-01-01

SUMMARY A common thread among conserved lifespan regulators lies within intertwined roles in metabolism and energy homeostasis. We show that heterozygous mutations of adenosine monophosphate (AMP) biosynthetic enzymes extend Drosophila lifespan. The lifespan benefit of these mutations depends upon increased AMP to adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to ATP ratios and adenosine monophosphate-activated protein kinase (AMPK). Transgenic expression of AMPK in adult fat body or adult muscle, key metabolic tissues, extended lifespan, while AMPK RNAi reduced lifespan. Supplementing adenine, a substrate for AMP biosynthesis, to the diet of long-lived AMP biosynthesis mutants reversed lifespan extension. Remarkably, this simple change in diet also blocked the pro-longevity effects of dietary restriction. These data establish AMP biosynthesis, adenosine nucleotide ratios, and AMPK as determinants of adult lifespan, provide a mechanistic link between cellular anabolism and energy sensing pathways, and indicate that dietary adenine manipulations might alter metabolism to influence animal lifespan. PMID:23312286

Longevity and mortality of owned dogs in England.

PubMed

O'Neill, D G; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C

2013-12-01

Improved understanding of longevity represents a significant welfare opportunity for the domestic dog, given its unparalleled morphological diversity. Epidemiological research using electronic patient records (EPRs) collected from primary veterinary practices overcomes many inherent limitations of referral clinic, owner questionnaire and pet insurance data. Clinical health data from 102,609 owned dogs attending first opinion veterinary practices (n=86) in central and southeast England were analysed, focusing on 5095 confirmed deaths. Of deceased dogs with information available, 3961 (77.9%) were purebred, 2386 (47.0%) were female, 2528 (49.8%) were neutered and 1105 (21.7%) were insured. The overall median longevity was 12.0 years (IQR 8.9-14.2). The longest-lived breeds were the Miniature poodle, Bearded collie, Border collie and Miniature dachshund, while the shortest-lived were the Dogue de Bordeaux and Great Dane. The most frequently attributed causes of death were neoplastic, musculoskeletal and neurological disorders. The results of multivariable modelling indicated that longevity in crossbred dogs exceeded purebred dogs by 1.2 years (95% confidence interval 0.9-1.4; P<0.001) and that increasing bodyweight was negatively correlated with longevity. The current findings highlight major breed differences for longevity and support the concept of hybrid vigour in dogs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Restoration longevity in an Australian Defence Force population.

PubMed

Dawson, A S; Smales, R J

1992-06-01

Replacement of restorations comprises a considerable portion of the work of most dentists. Consequently, factors that affect restoration longevity can influence the pattern of dental practice in a given community. Based on the results of research into treatment provision in the General Dental Service in Scotland, it was considered possible that factors such as the frequency with which patients were examined, and the frequency with which they changed dentists, might influence restoration longevity in other populations. Therefore, the present study was initiated to investigate the effects of these two factors in a population of 100 long-term members of the Royal Australian Air Force. No statistically significant relationship could be found between examination frequency, or frequent changes in dental practitioner, and restoration longevity. It is proposed that the large differences found in restoration longevity between this study and the Scottish study upon which it was based, may be due in part to the differing modes of remuneration of the dentists in the two studies.

Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

PubMed

Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

2015-08-01

Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Regulation of MIR Genes in Response to Abiotic Stress in Hevea brasiliensis

PubMed Central

Gébelin, Virginie; Leclercq, Julie; Hu, Songnian; Tang, Chaorong; Montoro, Pascal

2013-01-01

Increasing demand for natural rubber (NR) calls for an increase in latex yield and also an extension of rubber plantations in marginal zones. Both harvesting and abiotic stresses lead to tapping panel dryness through the production of reactive oxygen species. Many microRNAs regulated during abiotic stress modulate growth and development. The objective of this paper was to study the regulation of microRNAs in response to different types of abiotic stress and hormone treatments in Hevea. Regulation of MIR genes differs depending on the tissue and abiotic stress applied. A negative co-regulation between HbMIR398b with its chloroplastic HbCuZnSOD target messenger is observed in response to salinity. The involvement of MIR gene regulation during latex harvesting and tapping panel dryness (TPD) occurrence is further discussed. PMID:24084713

Calycophyllum spruceanum (Benth.), the Amazonian "Tree of Youth" Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans.

PubMed

Peixoto, Herbenya; Roxo, Mariana; Koolen, Hector; da Silva, Felipe; Silva, Emerson; Braun, Markus Santhosh; Wang, Xiaojuan; Wink, Michael

2018-02-27

The tree popularly known in Brazil as mulateiro or pau-mulato ( Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum . To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry)/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans . The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the "tree of youth", however more studies are needed to clarify its putative benefits to human health.

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

PubMed Central

Shor, Erika; Fox, Catherine A.; Broach, James R.

2013-01-01

Conditions of chronic stress are associated with genetic instability in many organisms, but the roles of stress responses in mutagenesis have so far been elucidated only in bacteria. Here, we present data demonstrating that the environmental stress response (ESR) in yeast functions in mutagenesis induced by proteotoxic stress. We show that the drug canavanine causes proteotoxic stress, activates the ESR, and induces mutagenesis at several loci in an ESR-dependent manner. Canavanine-induced mutagenesis also involves translesion DNA polymerases Rev1 and Polζ and non-homologous end joining factor Ku. Furthermore, under conditions of chronic sub-lethal canavanine stress, deletions of Rev1, Polζ, and Ku-encoding genes exhibit genetic interactions with ESR mutants indicative of ESR regulating these mutagenic DNA repair processes. Analyses of mutagenesis induced by several different stresses showed that the ESR specifically modulates mutagenesis induced by proteotoxic stress. Together, these results document the first known example of an involvement of a eukaryotic stress response pathway in mutagenesis and have important implications for mechanisms of evolution, carcinogenesis, and emergence of drug-resistant pathogens and chemotherapy-resistant tumors. PMID:23935537

Cell identity regulators link development and stress responses in the Arabidopsis root.

PubMed

Iyer-Pascuzzi, Anjali S; Jackson, Terry; Cui, Hongchang; Petricka, Jalean J; Busch, Wolfgang; Tsukagoshi, Hironaka; Benfey, Philip N

2011-10-18

Stress responses in plants are tightly coordinated with developmental processes, but interaction of these pathways is poorly understood. We used genome-wide assays at high spatiotemporal resolution to understand the processes that link development and stress in the Arabidopsis root. Our meta-analysis finds little evidence for a universal stress response. However, common stress responses appear to exist with many showing cell type specificity. Common stress responses may be mediated by cell identity regulators because mutations in these genes resulted in altered responses to stress. Evidence for a direct role for cell identity regulators came from genome-wide binding profiling of the key regulator SCARECROW, which showed binding to regulatory regions of stress-responsive genes. Coexpression in response to stress was used to identify genes involved in specific developmental processes. These results reveal surprising linkages between stress and development at cellular resolution, and show the power of multiple genome-wide data sets to elucidate biological processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Evolution, mutations, and human longevity: European royal and noble families.

PubMed

Gavrilova, N S; Gavrilov, L A; Evdokushkina, G N; Semyonova, V G; Gavrilova, A L; Evdokushkina, N N; Kushnareva, Y E; Kroutko, V N; Andreyev AYu

1998-08-01

The evolutionary theory of aging predicts that the equilibrium gene frequency for deleterious mutations should increase with age at onset of mutation action because of weaker (postponed) selection against later-acting mutations. According to this mutation accumulation hypothesis, one would expect the genetic variability for survival (additive genetic variance) to increase with age. The ratio of additive genetic variance to the observed phenotypic variance (the heritability of longevity) can be estimated most reliably as the doubled slope of the regression line for offspring life span on paternal age at death. Thus, if longevity is indeed determined by late-acting deleterious mutations, one would expect this slope to become steeper at higher paternal ages. To test this prediction of evolutionary theory of aging, we computerized and analyzed the most reliable and accurate genealogical data on longevity in European royal and noble families. Offspring longevity for each sex (8409 records for males and 3741 records for females) was considered as a dependent variable in the multiple regression model and as a function of three independent predictors: paternal age at death (for estimation of heritability of life span), paternal age at reproduction (control for parental age effects), and cohort life expectancy (control for cohort and secular trends and fluctuations). We found that the regression slope for offspring longevity as a function of paternal longevity increases with paternal longevity, as predicted by the evolutionary theory of aging and by the mutation accumulation hypothesis in particular.

MATERNAL TRAUMA AFFECTS PRENATAL MENTAL HEALTH AND INFANT STRESS REGULATION AMONG PALESTINIAN DYADS.

PubMed

Isosävi, Sanna; Diab, Safwat Y; Kangaslampi, Samuli; Qouta, Samir; Kankaanpää, Saija; Puura, Kaija; Punamäki, Raija-Leena

2017-09-01

We examined how diverse and cumulated traumatic experiences predicted maternal prenatal mental health and infant stress regulation in war conditions and whether maternal mental health mediated the association between trauma and infant stress regulation. Participants were 511 Palestinian mothers from the Gaza Strip who reported exposure to current war trauma (WT), past childhood emotional (CEA) and physical abuse, socioeconomic status (SES), prenatal mental health problems (posttraumatic stress disorder and depression symptoms), and perceived stress during their secondtrimester of pregnancy as well as infant stress regulation at 4 months. While all trauma types were associated with high levels of prenatal symptoms, CEA had the most wide-ranging effects and was uniquely associated with depression symptoms. Concerning infant stress regulation, mothers' CEA predicted negative affectivity, but only among mothers with low WT. Against hypothesis, the effects of maternal trauma on infant stress regulation were not mediated by mental health symptoms. Mothers' higher SES was associated with better infant stress regulation whereas infant prematurity and male sex predisposed for difficulties. Our findings suggest that maternal childhood abuse, especially CEA, should be a central treatment target among war-exposed families. Cumulated psychosocial stressors might increase the risk for transgenerational problems. © 2017 Michigan Association for Infant Mental Health.

Nitric Oxide Regulates Protein Methylation during Stress Responses in Plants.

PubMed

Hu, Jiliang; Yang, Huanjie; Mu, Jinye; Lu, Tiancong; Peng, Juli; Deng, Xian; Kong, Zhaosheng; Bao, Shilai; Cao, Xiaofeng; Zuo, Jianru

2017-08-17

Methylation and nitric oxide (NO)-based S-nitrosylation are highly conserved protein posttranslational modifications that regulate diverse biological processes. In higher eukaryotes, PRMT5 catalyzes Arg symmetric dimethylation, including key components of the spliceosome. The Arabidopsis prmt5 mutant shows severe developmental defects and impaired stress responses. However, little is known about the mechanisms regulating the PRMT5 activity. Here, we report that NO positively regulates the PRMT5 activity through S-nitrosylation at Cys-125 during stress responses. In prmt5-1 plants, a PRMT5 C125S transgene, carrying a non-nitrosylatable mutation at Cys-125, fully rescues the developmental defects, but not the stress hypersensitive phenotype and the responsiveness to NO during stress responses. Moreover, the salt-induced Arg symmetric dimethylation is abolished in PRMT5 C125S /prmt5-1 plants, correlated to aberrant splicing of pre-mRNA derived from a stress-related gene. These findings define a mechanism by which plants transduce stress-triggered NO signal to protein methylation machinery through S-nitrosylation of PRMT5 in response to environmental alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

Posttraumatic stress, difficulties in emotion regulation, and coping-oriented marijuana use.

PubMed

Bonn-Miller, Marcel O; Vujanovic, Anka A; Boden, Matthew Tyler; Gross, James J

2011-01-01

In an effort to better understand factors that may explain prior findings of a positive relation between posttraumatic stress symptom severity and coping-oriented marijuana use motivation, the present study tested whether the association between posttraumatic stress symptom severity and marijuana use coping motives is mediated by difficulties in emotion regulation. Participants were 79 (39 women; M(age) = 22.29 years, SD = 6.99) community-recruited adults who reported (1) lifetime exposure to at least one posttraumatic stress disorder Criterion A traumatic event and (2) marijuana use in the past 30 days. Results indicated that difficulties in emotion regulation, as indexed by the Difficulties in Emotion Regulation Scale (Gratz & Roemer, 2004), fully mediated the association between posttraumatic stress symptom severity and marijuana use coping motives. Implications for the treatment of co-occurring posttraumatic stress and marijuana use are discussed.

Lifestyle factors of people with exceptional longevity.

PubMed

Rajpathak, Swapnil N; Liu, Yingheng; Ben-David, Orit; Reddy, Saritha; Atzmon, Gil; Crandall, Jill; Barzilai, Nir

2011-08-01

To assess lifestyle factors including physical activity, smoking, alcohol consumption, and dietary habits in men and women with exceptional longevity. Retrospective cohort study. A cohort of community-dwelling Ashkenazi Jewish individuals with exceptional longevity defined as survival and living independently at age 95 and older. Four hundred seventy-seven individuals (mean 97.3 ± 2.8, range 95-109; 74.6% women) and a subset of participants of the National Health and Nutrition Examination Survey (NHANES) I (n = 3,164) representing the same birth cohort as a comparison group. A trained interviewer administrated study questionnaires to collect information on lifestyle factors and collected data on anthropometry. People with exceptional longevity had similar mean body mass index (men, 25.4 ± 2.8 kg/m² vs 25.6 ± 4.0 kg/m² , P=.63; women, 25.0 ± 3.5 kg/m² vs 24.9 ± 5.4 kg/m² ; P = .90) and a similar proportion of daily alcohol consumption (men, 23.9 vs 22.4, P = .77; women, 12.1 vs 11.3, P = .80), of regular physical activity (men: 43.1 vs 57.2; P = .07; women: 47.0 vs 44.1, P = .76), and of a low-calorie diet (men: 20.8 vs 21.1, P=.32; women: 27.3 vs 27.1, P=.14) as the NHANES I population. People with exceptional longevity are not distinct in terms of lifestyle factors from the general population, suggesting that people with exceptional longevity may interact with environmental factors differently than others. This requires further investigation. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Plant hormone-mediated regulation of stress responses.

PubMed

Verma, Vivek; Ravindran, Pratibha; Kumar, Prakash P

2016-04-14

Being sessile organisms, plants are often exposed to a wide array of abiotic and biotic stresses. Abiotic stress conditions include drought, heat, cold and salinity, whereas biotic stress arises mainly from bacteria, fungi, viruses, nematodes and insects. To adapt to such adverse situations, plants have evolved well-developed mechanisms that help to perceive the stress signal and enable optimal growth response. Phytohormones play critical roles in helping the plants to adapt to adverse environmental conditions. The elaborate hormone signaling networks and their ability to crosstalk make them ideal candidates for mediating defense responses. Recent research findings have helped to clarify the elaborate signaling networks and the sophisticated crosstalk occurring among the different hormone signaling pathways. In this review, we summarize the roles of the major plant hormones in regulating abiotic and biotic stress responses with special focus on the significance of crosstalk between different hormones in generating a sophisticated and efficient stress response. We divided the discussion into the roles of ABA, salicylic acid, jasmonates and ethylene separately at the start of the review. Subsequently, we have discussed the crosstalk among them, followed by crosstalk with growth promoting hormones (gibberellins, auxins and cytokinins). These have been illustrated with examples drawn from selected abiotic and biotic stress responses. The discussion on seed dormancy and germination serves to illustrate the fine balance that can be enforced by the two key hormones ABA and GA in regulating plant responses to environmental signals. The intricate web of crosstalk among the often redundant multitudes of signaling intermediates is just beginning to be understood. Future research employing genome-scale systems biology approaches to solve problems of such magnitude will undoubtedly lead to a better understanding of plant development. Therefore, discovering additional crosstalk

C. elegans sirtuin SIR-2.4 and its mammalian homolog SIRT6 in stress response.

PubMed

Jedrusik-Bode, Monika

2014-01-01

Stress is a significant life event. The immediate response to stress is critical for survival. In organisms ranging from the unicellular Saccharomyces cerevisiae to protozoa (Trypanosoma brucei) and metazoan (such as Caenorhabditis elegans, Homo sapiens) stress response leads to the formation of cytoplasmic RNA-protein complexes referred to as stress granules (SGs). SGs regulate cell survival during stress by the sequestration of the signaling molecules implicated in apoptosis. They are a transient place of messenger ribonucleoproteins (mRNPs) remodeling for storage, degradation, or reinitiation of translation during stress and recovery from stress. Recently, we have identified chromatin factor, the sirtuin C. elegans SIR-2.4 variant and its mammalian homolog SIRT6 as a regulator of SGs formation. SIRT6 is highly conserved NAD(+)-dependent lysine deacetylase and ADP-ribosyltransferase impacting longevity, metabolism, and cancer. We observed that the cellular formation of SGs by SIRT6 or SIR-2.4 was linked with the cell viability or C. elegans survival and was dependent on SIRT6 enzymatic activity. Here, we discuss how SIR-2.4/SIRT6 influences SGs formation and stress response. We suggest possible mechanisms for such an unanticipated function of a chromatin regulatory factor SIRT6 in assembly of stress granules and cellular stress resistance.

Duration of senescent cell survival in vitro as a characteristic of organism longevity, an additional to the proliferative potential of fibroblasts.

PubMed

Yegorov, Yegor E; Zelenin, Alexander V

2003-04-24

More than 40 years have passed since the original publication by Hayflick and Moorhead led to the concept of the 'Hayflick limit' of the maximum number of divisions which somatic cells undergo in vitro. This concept is still regarded as a fundamental characteristic of species longevity. Here we want to emphasize another characteristic of somatic cells, namely, the duration of their survival in vitro in the non-dividing state after cessation of proliferation. This is suggested on the basis of results of recent experiments with so-called Japanese accelerated senescent mice. Results of these experiments reveal a good correlation between the longevity of the mice, the number of duplications of their fibroblasts in vitro, and the survival time of these cells in the non-dividing state. In routine culture conditions, cell survival time may be very long, as much as a few years. However, when the cells are grown under conditions of oxidative stress, cellular longevity is markedly shortened. This new test may serve as an additional marker of organismic longevity. The comparative value of both tests, the classical 'Hayflick limit' and the new test, is discussed.

A microRNA regulates the response of corals to thermal stress.

PubMed

Gajigan, Andrian P; Conaco, Cecilia

2017-07-01

Coral reefs are diverse ecosystems of great ecological and economic importance. However, corals are vulnerable to a variety of stressors, including rising seawater temperatures, and yet little is known about the genetic mechanisms underlying their survival and adaptation to stress. Like other animals, corals possess genes for key members of the microRNA (miRNA) machinery. miRNAs are short RNAs that regulate diverse cellular processes, including organismal stress response, through post-transcriptional repression of gene transcripts. Through small RNA sequencing, we identified 26 miRNAs in the coral, Acropora digitifera. Many of the identified miRNAs are novel, while eight are conserved with miRNAs previously identified in other cnidarians. One of the identified miRNAs is differentially expressed in coral tissues exposed to acute thermal stress. This thermally responsive miRNA putatively regulates multiple pathways of the organismal stress response, DNA/RNA expression regulation, repair mechanisms, tissue morphogenesis, and signalling. We propose a model by which miRNA regulation allows the coral to mount a robust stress response through sequestration of a pool of nontranslated transcripts encoding stress response proteins. Release of miRNA-mediated repression under stress conditions may result in rapid and abundant translation of proteins that help the coral maintain cellular homoeostasis. These findings highlight the potential importance of miRNAs in the thermal resilience of corals. © 2017 John Wiley & Sons Ltd.

Ezrin Inhibition Up-regulates Stress Response Gene Expression*

PubMed Central

Çelik, Haydar; Bulut, Gülay; Han, Jenny; Graham, Garrett T.; Minas, Tsion Z.; Conn, Erin J.; Hong, Sung-Hyeok; Pauly, Gary T.; Hayran, Mutlu; Li, Xin; Özdemirli, Metin; Ayhan, Ayşe; Rudek, Michelle A.; Toretsky, Jeffrey A.; Üren, Aykut

2016-01-01

Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394. We identified and validated several up-regulated integrated stress response genes including PTGS2, ATF3, DDIT3, DDIT4, TRIB3, and ATF4 as novel ezrin-regulated transcripts. Analysis of transcriptional response in skin and peripheral blood mononuclear cells from NSC305787-treated mice compared with a control group revealed that, among those genes, the stress gene DDIT4/REDD1 may be used as a surrogate pharmacodynamic marker of ezrin inhibitor compound activity. In addition, we validated the anti-metastatic effects of NSC305787 in reducing the incidence of lung metastasis in a genetically engineered mouse model of osteosarcoma and evaluated the pharmacokinetics of NSC305787 and NSC668394 in mice. In conclusion, our findings suggest that cytoplasmic ezrin, previously considered a dormant and inactive protein, has important functions in regulating gene expression that may result in down-regulation of stress response genes. PMID:27137931

Serum Heat Shock Protein 70 Level as a Biomarker of Exceptional Longevity

PubMed Central

Terry, Dellara F.; Wyszynski, Diego F.; Nolan, Vikki G.; Atzmon, Gil; Schoenhofen, Emily A.; Pennington, JaeMi Y.; Andersen, Stacy L.; Wilcox, Marsha A.; Farrer, Lindsay A.; Barzilai, Nir; Baldwin, Clinton T.; Asea, Alexzander

2006-01-01

Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular Hsp70 has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 (Hsp70) for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.05, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes. PMID:17027907

Serum heat shock protein 70 level as a biomarker of exceptional longevity.

PubMed

Terry, Dellara F; Wyszynski, Diego F; Nolan, Vikki G; Atzmon, Gil; Schoenhofen, Emily A; Pennington, JaeMi Y; Andersen, Stacy L; Wilcox, Marsha A; Farrer, Lindsay A; Barzilai, Nir; Baldwin, Clinton T; Asea, Alexzander

2006-11-01

Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes.

Economic level and human longevity: Spatial and temporal variations and correlation analysis of per capita GDP and longevity indicators in China.

PubMed

Wang, Shaobin; Luo, Kunli; Liu, Yonglin; Zhang, Shixi; Lin, Xiaoxu; Ni, Runxiang; Tian, Xinglei; Gao, Xing

2015-01-01

We show the variation of longevity indicators in China during the past 60 years and its correlation patterns with per capita GDP (GDPpc) both at provincial and inner-provincial level. Population data from six national population censuses in China (1953-2010) at provincial level and in several typical provinces in 2010 at county-level were selected. Four main longevity indicators were calculated. Pearson's r and distributed lags time series analysis between longevity indicators and GDPpc were conducted. The results show that Guangxi and Hainan Provinces maintain relatively high long-lived population (population over the age of 90) across various population censuses. The distributions of the population over the age of 80 and life expectancy are significantly affected by both contemporaneous and historical GDPpc at provincial level. However, areas of high long-lived population (over the age of 90) exhibit continuously stable features that lack any significant correlation with GDPpc both at provincial and inner-provincial level. Our results indicate a mixed distribution pattern of several longevity indexes and different relation to GDPpc. It shows consistent trend with Preston curve, that is, economic conditions may have limited influence on human longevity, especially for those who live longer than 90 years old. This study suggests that the economic development may favor the local residents to have access to live as old as 80 years old, but it is still difficult for most residents to reach the level of centenarians. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Book Longevity. Reports of the Committee on Production Guidelines for Book Longevity.

ERIC Educational Resources Information Center

Bailey, Herbert S., Jr.; And Others

In 1979, a Committee on Production Guidelines for Book Longevity was formed to study some aspects of the book preservation problem. Composed of representatives from libraries, publishing, and the paper industry, the committee set two primary objectives: to increase knowledge about the durability of books and other materials, and to encourage…

Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice.

PubMed

Mendias, Christopher L; Bakhurin, Konstantin I; Gumucio, Jonathan P; Shallal-Ayzin, Mark V; Davis, Carol S; Faulkner, John A

2015-08-01

The molecular mechanisms behind aging-related declines in muscle function are not well understood, but the growth factor myostatin (MSTN) appears to play an important role in this process. Additionally, epidemiological studies have identified a positive correlation between skeletal muscle mass and longevity. Given the role of myostatin in regulating muscle size, and the correlation between muscle mass and longevity, we tested the hypotheses that the deficiency of myostatin would protect oldest-old mice (28-30 months old) from an aging-related loss in muscle size and contractility, and would extend the maximum lifespan of mice. We found that MSTN(+/-) and MSTN(-/-) mice were protected from aging-related declines in muscle mass and contractility. While no differences were detected between MSTN(+/+) and MSTN(-/-) mice, MSTN(+/-) mice had an approximately 15% increase in maximal lifespan. These results suggest that targeting myostatin may protect against aging-related changes in skeletal muscle and contribute to enhanced longevity. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Innate immunity mediated longevity and longevity induced by germ cell removal converge on the C-type lectin domain protein IRG-7

PubMed Central

Yunger, Elad; Safra, Modi; Levi-Ferber, Mor; Haviv-Chesner, Anat

2017-01-01

In C. elegans, removal of the germline triggers molecular events in the neighboring intestine, which sends an anti-aging signal to the rest of the animal. In this study, we identified an innate immunity related gene, named irg-7, as a novel mediator of longevity in germlineless animals. We consider irg-7 to be an integral downstream component of the germline longevity pathway because its expression increases upon germ cell removal and its depletion interferes with the activation of the longevity-promoting transcription factors DAF-16 and DAF-12 in germlineless animals. Furthermore, irg-7 activation by itself sensitizes the animals' innate immune response and extends the lifespan of animals exposed to live bacteria. This lifespan-extending pathogen resistance relies on the somatic gonad as well as on many genes previously associated with the reproductive longevity pathway. This suggests that these genes are also relevant in animals with an intact gonad, and can affect their resistance to pathogens. Altogether, this study demonstrates the tight association between germline homeostasis and the immune response of animals, and raises the possibility that the reproductive system can act as a signaling center to divert resources towards defending against putative pathogen attacks. PMID:28196094

Ezrin Inhibition Up-regulates Stress Response Gene Expression.

PubMed

Çelik, Haydar; Bulut, Gülay; Han, Jenny; Graham, Garrett T; Minas, Tsion Z; Conn, Erin J; Hong, Sung-Hyeok; Pauly, Gary T; Hayran, Mutlu; Li, Xin; Özdemirli, Metin; Ayhan, Ayşe; Rudek, Michelle A; Toretsky, Jeffrey A; Üren, Aykut

2016-06-17

Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394. We identified and validated several up-regulated integrated stress response genes including PTGS2, ATF3, DDIT3, DDIT4, TRIB3, and ATF4 as novel ezrin-regulated transcripts. Analysis of transcriptional response in skin and peripheral blood mononuclear cells from NSC305787-treated mice compared with a control group revealed that, among those genes, the stress gene DDIT4/REDD1 may be used as a surrogate pharmacodynamic marker of ezrin inhibitor compound activity. In addition, we validated the anti-metastatic effects of NSC305787 in reducing the incidence of lung metastasis in a genetically engineered mouse model of osteosarcoma and evaluated the pharmacokinetics of NSC305787 and NSC668394 in mice. In conclusion, our findings suggest that cytoplasmic ezrin, previously considered a dormant and inactive protein, has important functions in regulating gene expression that may result in down-regulation of stress response genes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Gamma-oryzanol rich fraction regulates the expression of antioxidant and oxidative stress related genes in stressed rat's liver.

PubMed

Ismail, Maznah; Al-Naqeeb, Ghanya; Mamat, Wan Abd Aziz Bin; Ahmad, Zalinah

2010-03-24

Gamma-oryzanol (OR), a phytosteryl ferulate mixture extracted from rice bran oil, has a wide spectrum of biological activities in particular, it has antioxidant properties. The regulatory effect of gamma-oryzanol rich fraction (ORF) extracted and fractionated from rice bran using supercritical fluid extraction (SFE) in comparison with commercially available OR on 14 antioxidant and oxidative stress related genes was determined in rat liver. Rats were subjected to a swimming exercise program for 10 weeks to induce stress and were further treated with either ORF at 125, 250 and 500 mg/kg or OR at 100 mg/kg in emulsion forms for the last 5 weeks of the swimming program being carried out. The GenomeLab Genetic Analysis System (GeXPS) was used to study the multiplex gene expression of the selected genes. Upon comparison of RNA expression levels between the stressed and untreated group (PC) and the unstressed and untreated group (NC), seven genes were found to be down-regulated, while seven genes were up-regulated in PC group compared to NC group. Further treatment of stressed rats with ORF at different doses and OR resulted in up-regulation of 10 genes and down regulation of four genes compared to the PC group. Gamma-oryzanol rich fraction showed potential antioxidant activity greater than OR in the regulation of antioxidants and oxidative stress gene markers.

Gamma-oryzanol rich fraction regulates the expression of antioxidant and oxidative stress related genes in stressed rat's liver

PubMed Central

2010-01-01

Background Gamma-oryzanol (OR), a phytosteryl ferulate mixture extracted from rice bran oil, has a wide spectrum of biological activities in particular, it has antioxidant properties. Methods The regulatory effect of gamma-oryzanol rich fraction (ORF) extracted and fractionated from rice bran using supercritical fluid extraction (SFE) in comparison with commercially available OR on 14 antioxidant and oxidative stress related genes was determined in rat liver. Rats were subjected to a swimming exercise program for 10 weeks to induce stress and were further treated with either ORF at 125, 250 and 500 mg/kg or OR at 100 mg/kg in emulsion forms for the last 5 weeks of the swimming program being carried out. The GenomeLab Genetic Analysis System (GeXPS) was used to study the multiplex gene expression of the selected genes. Results Upon comparison of RNA expression levels between the stressed and untreated group (PC) and the unstressed and untreated group (NC), seven genes were found to be down-regulated, while seven genes were up-regulated in PC group compared to NC group. Further treatment of stressed rats with ORF at different doses and OR resulted in up-regulation of 10 genes and down regulation of four genes compared to the PC group. Conclusions Gamma-oryzanol rich fraction showed potential antioxidant activity greater than OR in the regulation of antioxidants and oxidative stress gene markers. PMID:20331906

National Pork Producers Council Maternal Line National Genetic Evaluation Program: a comparison of sow longevity and trait associations with sow longevity.

PubMed

Serenius, T; Stalder, K J; Baas, T J; Mabry, J W; Goodwin, R N; Johnson, R K; Robison, O W; Tokach, M; Miller, R K

2006-09-01

Data from the National Pork Producers Council Maternal Line National Genetic Evaluation Program were used to compare longevity of sows from 6 commercial genetic lines and to estimate the phenotypic associations of sow longevity with gilt backfat thickness, ADG, age at first farrowing, litter size at first farrowing, litter weight at first farrowing, average feed intake during lactation, and average backfat loss during lactation. The lines evaluated were American Diamond Genetics, Danbred North America, Dekalb-Monsanto DK44, Dekalb-Monsanto GPK347, Newsham Hybrids, and National Swine Registry. The data set contained information from 3,251 gilts, of which 17% had censored longevity records (sows lived longer than 6 parities). The line comparison was carried out by analyzing all lines simultaneously. Because the survival distribution functions differed among genetic lines, later analyses were carried out separately for each genetic line. All analyses were based on the non-parametric proportional hazard (Cox model). Dekalb-Monsanto GPK347 sows had a lower risk of being culled than sows from the other lines. Moreover, the shape of the survival distribution function of the Delkab-Monsanto GPK347 line was different from the other 5 lines. The Dekalb-Monsanto 347 line had lower culling rates because they had lower gilt reproductive failure before the first parity than gilts from the other lines. Within line, sows with lower feed intake and greater backfat loss during lactation had a shorter productive lifetime. Thus, producers should implement management practices having positive effects on sow lactation feed intake. Additionally, the swine genetics industry is challenged to simultaneously improve efficiency of gain of their terminal market pigs and to obtain high feed intake during lactation of their maternal lines for future improvement of sow longevity. Recording sow feed intake and backfat loss during lactation in nucleus and multiplication breeding herds should be

A prospective study of associations among helping, health, and longevity.

PubMed

Hilbrand, Sonja; Coall, David A; Meyer, Andrea H; Gerstorf, Denis; Hertwig, Ralph

2017-08-01

How does helping behavior contribute to the health and the longevity of older helpers? From an evolutionary perspective, the ultimate cause may be rooted in ancestral parenting and grandparenting. These activities may have generalized to a neural and hormonal caregiving system that also enabled prosocial behavior beyond the family. From a psychological perspective, helping others may be associated with healthy aging, which, in turn, contributes to longevity as a proximate cause. Yet little is known about the extent to which mediating factors such as the health benefits of helping behaviors translate into enhanced longevity, particularly in regard to grandparenting. To fill this gap, we conducted mediation analyses (structural equation models) to examine whether grandparenting and supporting others in the social network contributed directly or indirectly (through better health 5-6 years later) to the longevity of older helpers. We drew on longitudinal data from the Berlin Aging Study (N = 516), in which older adults in Berlin, Germany, were interviewed at baseline (1990-1993, mean age at entry = 85 years) and continuously followed up until 2009. Results suggest that the associations of both grandparenting and supporting others with enhanced longevity are mediated by better prospective health (indirect effect). The effect of helping was not fully mediated, however-helping was also directly associated with increased longevity independently of the health indicators measured. The results were robust against effects of the helper's preexisting health status and sociodemographic characteristics of participants, their children, and grandchildren. We conclude that better prospective health contributes to the link between helping and longevity, but does not fully account for it. Other potential contributing mechanisms remain to be identified. As populations age across the globe, identifying mechanisms that foster health in old age can help to highlight potential targets

Mechanical stress regulation of plant growth and development

NASA Technical Reports Server (NTRS)

Mitchell, C. A.; Myers, P. N.

1995-01-01

The authors introduce the chapter with a discussion of lessons from nature, agriculture, and landscapes; terms and definitions; and an historical perspective of mechanical stress regulation of plant growth and development. Topics include developmental responses to mechanical stress; mechanical stress-environment interactions; metabolic, productivity, and compositional changes; hormonal involvement; mechanoperception and early transduction mechanisms; applications in agriculture; and research implications. The discussion of hormonal involvement in mechanical stress physiology includes ethylene, auxin, gibberellins, and other phytohormones. The discussion of applications in agriculture examines windbreaks, nursery practices, height control and conditioning, and enhancement of growth and productivity. Implications for research are related to handling plant materials, space biology, and future research needs.

MOF maintains transcriptional programs regulating cellular stress response

PubMed Central

Sheikh, B N; Bechtel-Walz, W; Lucci, J; Karpiuk, O; Hild, I; Hartleben, B; Vornweg, J; Helmstädter, M; Sahyoun, A H; Bhardwaj, V; Stehle, T; Diehl, S; Kretz, O; Voss, A K; Thomas, T; Manke, T; Huber, T B; Akhtar, A

2016-01-01

MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes. PMID:26387537

MOF maintains transcriptional programs regulating cellular stress response.

PubMed

Sheikh, B N; Bechtel-Walz, W; Lucci, J; Karpiuk, O; Hild, I; Hartleben, B; Vornweg, J; Helmstädter, M; Sahyoun, A H; Bhardwaj, V; Stehle, T; Diehl, S; Kretz, O; Voss, A K; Thomas, T; Manke, T; Huber, T B; Akhtar, A

2016-05-01

MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes.

Proteomic analysis shows that stress response proteins are significantly up-regulated in resistant diploid wheat (Triticum monococcum) in response to attack by the grain aphid (Sitobion avenae).

PubMed

Guan, Wenzhu; Ferry, Natalie; Edwards, Martin G; Bell, Howard A; Othman, Hamizah; Gatehouse, John A; Gatehouse, Angharad M R

2015-01-01

The grain aphid Sitobion avenae (F.) is a major pest of wheat, acting as a virus vector as well as causing direct plant damage. Commonly grown wheat varieties in the UK have only limited resistance to this pest. The present study was carried out to investigate the potential of a diploid wheat line (ACC20 PGR1755), reported as exhibiting resistance to S. avenae, to serve as a source of resistance genes. The diploid wheat line was confirmed as partially resistant, substantially reducing the fecundity, longevity and growth rate of the aphid. Proteomic analysis showed that approximately 200 protein spots were reproducibly detected in leaf extracts from both the resistant line and a comparable susceptible line (ACC5 PGR1735) using two-dimensional gel electrophoresis and image comparison software. Twenty-four spots were significantly up-regulated (>2-fold) in the resistant line after 24 h of aphid feeding (13 and 11 involved in local and systemic responses, respectively). Approximately 50 % of all differentially expressed protein spots were identified by a combination of database searching with MS and MS/MS data, revealing that the majority of proteins up-regulated by aphid infestation were involved in metabolic processes (including photosynthesis) and transcriptional regulation. However, in the resistant line only, several stress response proteins (including NBS-LRR-like proteins) and oxidative stress response proteins were identified as up-regulated in response to aphid feeding, as well as proteins involved in DNA synthesis/replication/repair. This study indicates that the resistant diploid line ACC20 PGR1755 may provide a valuable resource in breeding wheat for resistance to aphids.

Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.

PubMed

Revelas, Mary; Thalamuthu, Anbupalam; Oldmeadow, Christopher; Evans, Tiffany-Jane; Armstrong, Nicola J; Kwok, John B; Brodaty, Henry; Schofield, Peter R; Scott, Rodney J; Sachdev, Perminder S; Attia, John R; Mather, Karen A

2018-06-08

Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts. Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males). In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls. Copyright © 2018. Published by Elsevier B.V.

Positive emotion word use and longevity in famous deceased psychologists.

PubMed

Pressman, Sarah D; Cohen, Sheldon

2012-05-01

This study examined whether specific types of positive and negative emotional words used in the autobiographies of well-known deceased psychologists were associated with longevity. For each of the 88 psychologists, the percent of emotional words used in writing was calculated and categorized by valence (positive or negative) and arousal (activated [e.g., lively, anxious] or not activated [e.g., calm, drowsy]) based on existing emotion scales and models of emotion categorization. After controlling for sex, year of publication, health (based on disclosed illness in autobiography), native language, and year of birth, the use of more activated positive emotional words (e.g., lively, vigorous, attentive, humorous) was associated with increased longevity. Negative terms (e.g., angry, afraid, drowsy, sluggish) and unactivated positive terms (e.g., peaceful, calm) were not related to longevity. The association of activated positive emotions with longevity was also independent of words indicative of social integration, optimism, and the other affect/activation categories. Results indicate that in writing, not every type of emotion correlates with longevity and that there may be value to considering different categories beyond emotional valence in health relevant outcomes.

Juvenile stress impairs body temperature regulation and augments anticipatory stress-induced hyperthermia responses in rats.

PubMed

Yee, Nicole; Plassmann, Kerstin; Fuchs, Eberhard

2011-09-01

Clinical studies have implicated adolescence as an important and vulnerable period during which traumatic experiences can predispose individuals to anxiety and mood disorders. As such, a stress model in juvenile rats (age 27-29 d) was previously developed to investigate the long-term effects of stress exposure during adolescence on behavior and physiology. This paradigm involves exposing rats to different stressors on consecutive days over a 3-day period. Here, we studied the effects of juvenile stress on long-term core body temperature regulation and acute stress-induced hyperthermia (SIH) responses using telemetry. We found no differences between control and juvenile stress rats in anxiety-related behavior on the elevated plus maze, which we attribute to stress associated with surgical implantation of telemetry devices. This highlights the severe impact of surgical stress on the results of subsequent behavioral measurements. Nonetheless, juvenile stress disrupted the circadian rhythmicity of body temperature and decreased circadian amplitude. It also induced chronic hypothermia during the dark phase of the day, when rats are most active. When subjected to acute social defeat stress as adults, juvenile stress had no impact on the SIH response relative to controls. However, 24 h later, juvenile stress rats displayed an elevated SIH response in anticipation of social defeat when re-exposed to the social defeat environment. Taken together, our findings indicate that juvenile stress can induce long-term alterations in body temperature regulation and heighten the increase in temperature associated with anticipation of social defeat. The outcomes of behavioral measurements in these experiments, however, are severely affected by surgical stress. Copyright © 2011 Elsevier Inc. All rights reserved.

Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation

PubMed Central

Rodgers, Ali B.; Morgan, Christopher P.; Bronson, Stefanie L.; Revello, Sonia; Bale, Tracy L.

2013-01-01

Neuropsychiatric disease frequently presents with an underlying hypo- or hyper- reactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic-pituitary-adrenal (HPA) axis dysregulation, we exposed mice to six weeks of chronic stress prior to breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA axis stress responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis (BNST), revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm miRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk. PMID:23699511

Drosophila melanogaster activating transcription factor 4 regulates glycolysis during endoplasmic reticulum stress.

PubMed

Lee, Ji Eun; Oney, McKenna; Frizzell, Kimberly; Phadnis, Nitin; Hollien, Julie

2015-02-13

Endoplasmic reticulum (ER) stress results from an imbalance between the load of proteins entering the secretory pathway and the ability of the ER to fold and process them. The response to ER stress is mediated by a collection of signaling pathways termed the unfolded protein response, which plays important roles in development and disease. Here we show that in Drosophila melanogaster S2 cells, ER stress induces a coordinated change in the expression of genes involved in carbon metabolism. Genes encoding enzymes that carry out glycolysis were up-regulated, whereas genes encoding proteins in the tricarboxylic acid cycle and respiratory chain complexes were down-regulated. The unfolded protein response transcription factor Atf4 was necessary for the up-regulation of glycolytic enzymes and Lactate dehydrogenase (Ldh). Furthermore, Atf4 binding motifs in promoters for these genes could partially account for their regulation during ER stress. Finally, flies up-regulated Ldh and produced more lactate when subjected to ER stress. Together, these results suggest that Atf4 mediates a shift from a metabolism based on oxidative phosphorylation to one more heavily reliant on glycolysis, reminiscent of aerobic glycolysis or the Warburg effect observed in cancer and other proliferative cells. Copyright © 2015 Lee et al.

Drosophila melanogaster Activating Transcription Factor 4 Regulates Glycolysis During Endoplasmic Reticulum Stress

PubMed Central

Lee, Ji Eun; Oney, McKenna; Frizzell, Kimberly; Phadnis, Nitin; Hollien, Julie

2015-01-01

Endoplasmic reticulum (ER) stress results from an imbalance between the load of proteins entering the secretory pathway and the ability of the ER to fold and process them. The response to ER stress is mediated by a collection of signaling pathways termed the unfolded protein response, which plays important roles in development and disease. Here we show that in Drosophila melanogaster S2 cells, ER stress induces a coordinated change in the expression of genes involved in carbon metabolism. Genes encoding enzymes that carry out glycolysis were up-regulated, whereas genes encoding proteins in the tricarboxylic acid cycle and respiratory chain complexes were down-regulated. The unfolded protein response transcription factor Atf4 was necessary for the up-regulation of glycolytic enzymes and Lactate dehydrogenase (Ldh). Furthermore, Atf4 binding motifs in promoters for these genes could partially account for their regulation during ER stress. Finally, flies up-regulated Ldh and produced more lactate when subjected to ER stress. Together, these results suggest that Atf4 mediates a shift from a metabolism based on oxidative phosphorylation to one more heavily reliant on glycolysis, reminiscent of aerobic glycolysis or the Warburg effect observed in cancer and other proliferative cells. PMID:25681259

Lipoprotein Particle Profiles Mark Familial and Sporadic Human Longevity

PubMed Central

Heijmans, Bastiaan T; Beekman, Marian; Houwing-Duistermaat, Jeanine J; Cobain, Mark R; Powell, Jonathan; Blauw, Gerard Jan; van der Ouderaa, Frans; Westendorp, Rudi G. J; Slagboom, P. Eline

2006-01-01

Background Genetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population. Methods and Findings NMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10−3) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007). Conclusions Our study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age. PMID:17194192

Academic Stress and Self-Regulation among University Students in Malaysia: Mediator Role of Mindfulness

PubMed Central

Hj Ramli, Nur Hamizah; Alavi, Masoumeh; Mehrinezhad, Seyed Abolghasem; Ahmadi, Atefeh

2018-01-01

Academic stress is the most common emotional or mental state that students experience during their studies. Stress is a result of a wide range of issues, including test and exam burden, a demanding course, a different educational system, and thinking about future plans upon graduation. A sizeable body of literature in stress management research has found that self-regulation and being mindful will help students to cope up with the stress and dodge long-term negative consequences, such as substance abuse. The present study aims to investigate the influence of academic stress, self-regulation, and mindfulness among undergraduate students in Klang Valley, Malaysia, and to identify mindfulness as the mediator between academic stress and self-regulation. For this study, a total of 384 undergraduate students in Klang Valley, Malaysia were recruited. Using Correlational analysis, results revealed that there was a significant relationship between academic stress, self-regulation, and mindfulness. However, using SPSS mediational analysis, mindfulness did not prove the mediator role in the study. PMID:29342910

Academic Stress and Self-Regulation among University Students in Malaysia: Mediator Role of Mindfulness.

PubMed

Hj Ramli, Nur Hamizah; Alavi, Masoumeh; Mehrinezhad, Seyed Abolghasem; Ahmadi, Atefeh

2018-01-15

Academic stress is the most common emotional or mental state that students experience during their studies. Stress is a result of a wide range of issues, including test and exam burden, a demanding course, a different educational system, and thinking about future plans upon graduation. A sizeable body of literature in stress management research has found that self-regulation and being mindful will help students to cope up with the stress and dodge long-term negative consequences, such as substance abuse. The present study aims to investigate the influence of academic stress, self-regulation, and mindfulness among undergraduate students in Klang Valley, Malaysia, and to identify mindfulness as the mediator between academic stress and self-regulation. For this study, a total of 384 undergraduate students in Klang Valley, Malaysia were recruited. Using Correlational analysis, results revealed that there was a significant relationship between academic stress, self-regulation, and mindfulness. However, using SPSS mediational analysis, mindfulness did not prove the mediator role in the study.

Necessity of angiotensin-converting enzyme-related gene for cardiac functions and longevity of Drosophila melanogaster assessed by optical coherence tomography

NASA Astrophysics Data System (ADS)

Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan

2014-01-01

Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.

Host-pathogen dynamics under sterilizing pathogens and fecundity-longevity trade-off in hosts.

PubMed

Janoušková, Eva; Berec, Luděk

2018-08-07

Infectious diseases are known to regulate population dynamics, an observation that underlies the use of pathogens as control agents of unwanted populations. Sterilizing rather than lethal pathogens are often suggested so as to avoid unnecessary suffering of the infected hosts. Until recently, models used to assess plausibility of pathogens as potential pest control agents have not included a possibility that reduced fecundity of the infected individuals may save their energy expenditure on reproduction and thus increase their longevity relative to the susceptible ones. Here, we develop a model of host-pathogen interaction that builds on this idea. We analyze the model for a variety of infection transmission functions, revealing that the indirect effect of sterilizing pathogens on mortality of the infected hosts, mediated by a fecundity-longevity trade-off, may cause hosts at endemic equilibria to attain densities higher than when there is no effect of pathogens on host mortality. On the other hand, an opposite outcome occurs when the fecundity-longevity trade-off is concave or when the degree of fecundity reduction by the pathogen is high enough. This points to a possibility that using sterilizing pathogens as agents of pest control may actually be less effective than previously thought, the more so since we also suggest that if sexual selection acts on the host species then the presence of sterilizing pathogens may even enhance host densities above the levels achieved without infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Regulation of water, salinity, and cold stress responses by salicylic acid

PubMed Central

Miura, Kenji; Tada, Yasuomi

2014-01-01

Salicylic acid (SA) is a naturally occurring phenolic compound. SA plays an important role in the regulation of plant growth, development, ripening, and defense responses. The role of SA in the plant–pathogen relationship has been extensively investigated. In addition to defense responses, SA plays an important role in the response to abiotic stresses, including drought, low temperature, and salinity stresses. It has been suggested that SA has great agronomic potential to improve the stress tolerance of agriculturally important crops. However, the utility of SA is dependent on the concentration of the applied SA, the mode of application, and the state of the plants (e.g., developmental stage and acclimation). Generally, low concentrations of applied SA alleviate the sensitivity to abiotic stresses, and high concentrations of applied induce high levels of oxidative stress, leading to a decreased tolerance to abiotic stresses. In this article, the effects of SA on the water stress responses and regulation of stomatal closure are reviewed. PMID:24478784

Increased Rate of NAD Metabolism Shortens Plant Longevity by Accelerating Developmental Senescence in Arabidopsis.

PubMed

Hashida, Shin-Nosuke; Itami, Taketo; Takahara, Kentaro; Hirabayashi, Takayuki; Uchimiya, Hirofumi; Kawai-Yamada, Maki

2016-11-01

NAD is a well-known co-enzyme that mediates hundreds of redox reactions and is the basis of various processes regulating cell responses to different environmental and developmental cues. The regulatory mechanism that determines the amount of cellular NAD and the rate of NAD metabolism remains unclear. We created Arabidopsis thaliana plants overexpressing the NAD synthase (NADS) gene that participates in the final step of NAD biosynthesis. NADS overexpression enhanced the activity of NAD biosynthesis but not the amounts of NAD + , NADH, NADP + or NADPH. However, the amounts of some intermediates were elevated, suggesting that NAD metabolism increased. The NAD redox state was greatly facilitated by an imbalance between NAD generation and degradation in response to bolting. Metabolite profiling and transcriptional analysis revealed that the drastic modulation of NAD redox homeostasis increased tricarboxylic acid flux, causing the ectopic generation of reactive oxygen species. Vascular bundles suffered from oxidative stress, leading to a malfunction in amino acid and organic acid transportation that caused early wilting of the flower stalk and shortened plant longevity, probably due to malnutrition. We concluded that the mechanism regulating the balance between NAD synthesis and degradation is important in the systemic plant response to developmental cues during the growth-phase transition. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Symbolic significance of initials on longevity.

PubMed

Abel, Ernest L; Kruger, Michael L

2007-02-01

The longevities of deceased major league baseball players who died prior to 1950 (N=3835) and whose initials formed acronyms, words, or names with "positive" or "negative" affect, as rated a priori by two judges, were compared with those for a group of neutral controls matched for birth year and career length, using the Berkeley standardized mortality tables. Players (n=11) with positive initials, e.g., A.C.E., lived a mean of 13 years longer than players (n=30) with negative initials, e.g., D.E.D., or players with neutral initials (n=864). These results corroborated a previous study and suggest positive name symbols are associated with increased longevity in this sample.

3β-Hydroxy-urs-12-en-28-oic Acid Modulates Dietary Restriction Mediated Longevity and Ameliorates Toxic Protein Aggregation in C. elegans.

PubMed

Negi, Hema; Saikia, Shilpi Khare; Pandey, Rakesh

2017-11-09

Species from lower invertebrates to a spectrum of mammals show antiaging health benefits of phytochemical(s). Here, we explored the pro-longevity effects of a natural triterpenoid, ursolic acid (3β-hydroxy-urs-12-en-28-oic acid; UA) in Caenorhabditis elegans with maximal life span being evident at 25 µM UA. Similar to eat-2 mutants, UA uptake by worm results in reduced fat storage and attenuation of reactive oxygen species (ROS), independent of superoxide dismutase(s) activation. The genetic requirements for UA-mediated longevity are quite similar to dietary restriction (DR) achieved through SKN-1/NRF-2 exhibiting upregulation of downstream target genes gcs-1 and daf-9. Longevity mechanism was independent of PHA-4/FOXA and attributed to partial dependence on sir-2.1. Altogether, our study suggests differential use of UA-elicited signaling cascades in nutrient sensing for longevity. Both the redox state and the proteostasis of an organism play critical role in aging and disease resistance. Interestingly, we observed a reduction of toxic protein aggregation in transgenic polyglutamine (polyQ) C. elegans model and UA-mediated JNK-1 (c-Jun-NH2-terminal kinase) activation in wild-type animals. Thus, our study demonstrates a small extent of prevention against proteotoxic stress by UA coupled with positive aspects of DR-mediated longevity. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The pursuit of longevity - the bringer of peace to the middle East.

PubMed

Stambler, Ilia

2014-01-01

Despite the common apprehensions regarding the aging population, this work aims to argue, on both deontological and utilitarian moral grounds, that any increase in general life-expectancy will be beneficial for the Middle East, countering the common fears associated with this increase. A set of ethical arguments concerning increasing longevity is presented, from both the deontological and utilitarian perspective. A wide selection of economic, psychological, demographic and epidemiological literature and databases is analyzed to determine common correlates of extended longevity. On the deontological grounds, the value of extended longevity is derived from the value of life preservation, regardless of its term. On the utilitarian grounds, the value of extended longevity is demonstrated by its correlation with further human values, such as education level and intellectual activity, economic prosperity, equality, solidarity and peacefulness. With the common apprehensions of stagnation and scarcity due to life extension found wanting, the pursuit of longevity by the population can be seen as a cross-cultural and cross-generational good. Though the current study mainly refers to sources and data relevant to the Middle East, a similar pro-longevity argument can be also made for other cultural contexts. In view of its numerous benefits, normatively, the goal of longevity should be set clearly and openly by the society, and actively pursued, or at least discussed, in academia, the political system and broader public.

Personality predictors of longevity: Activity, Emotional Stability, and Conscientiousness

PubMed Central

Terracciano, Antonio; Löckenhoff, Corinna E.; Zonderman, Alan B.; Ferrucci, Luigi; Costa, Paul T.

2008-01-01

Objective To examine the association between personality traits and longevity. Methods Using the Guilford-Zimmerman Temperament Survey, personality traits were assessed in 2359 participants (38% women; age: 17 to 98 years, M = 50) from the Baltimore Longitudinal Study of Aging (BLSA), starting in 1958. Over the duration of the study, 943 (40%) participants died, on average 18 years after their personality assessment. The association of each trait with longevity was examined by Cox regression controlling for demographic variables. Results In preliminary analyses among the deceased, those who scored one SD above the mean on General Activity (a facet of Extraversion), Emotional Stability (low Neuroticism), or Conscientiousness lived on average two to three years longer than those scoring one SD below the mean. Survival analyses on the full sample confirmed the association of General Activity, Emotional Stability, and Conscientiousness with lower risk of death, such that every one SD increase was related to about 13%, 15%, and 27% risk reduction, respectively. The association of personality traits with longevity was largely independent from the influence of smoking and obesity. Personality predictors of longevity did not differ by sex, except for Ascendance (a facet of Extraversion). Emotional Stability was a significant predictor when the analyses were limited to deaths due to cardiovascular disease, with comparable effect sizes for General Activity and Conscientiousness. Conclusions In a large sample of generally healthy individuals followed for almost five decades, longevity was associated with being conscientious, emotionally stable, and active. PMID:18596250

Personality predictors of longevity: activity, emotional stability, and conscientiousness.

PubMed

Terracciano, Antonio; Löckenhoff, Corinna E; Zonderman, Alan B; Ferrucci, Luigi; Costa, Paul T

2008-07-01

To examine the association between personality traits and longevity. Using the Guilford-Zimmerman Temperament Survey, personality traits were assessed in 2359 participants (38% women; age = 17 to 98 years, mean = 50 years) from the Baltimore Longitudinal Study of Aging, starting in 1958. Over the duration of the study, 943 (40%) participants died, on average 18 years after their personality assessment. The association of each trait with longevity was examined by Cox regression controlling for demographic variables. In preliminary analyses among the deceased, those who scored 1 standard deviation (SD) above the mean on General Activity (a facet of Extraversion), Emotional Stability (low Neuroticism), or Conscientiousness lived on average 2 to 3 years longer than those scoring 1 SD below the mean. Survival analyses on the full sample confirmed the association of General Activity, Emotional Stability, and Conscientiousness with lower risk of death, such that every 1-SD increase was related to about 13%, 15%, and 27% risk reduction, respectively. The association of personality traits with longevity was largely independent from the influence of smoking and obesity. Personality predictors of longevity did not differ by sex, except for Ascendance (a facet of Extraversion). Emotional Stability was a significant predictor when the analyses were limited to deaths due to cardiovascular disease, with comparable effect sizes for General Activity and Conscientiousness. In a large sample of generally healthy individuals followed for almost five decades, longevity was associated with being conscientious, emotionally stable, and active.

The challenges in moving from ageing to successful longevity.

PubMed

Kolovou, Genovefa; Barzilai, Nir; Caruso, Calogero; Sikora, Ewa; Capri, Miriam; Tzanetakou, Irene P; Bilianou, Helen; Avery, Peter; Katsiki, Niki; Panotopoulos, George; Franceschi, Claudio; Benetos, Athanase; Mikhailidis, Dimitri P

2014-01-01

During the last decades survival has significantly improved and centenarians are becoming a fast-growing group of the population. Human life span is mainly dependent on environmental and genetic factors. Favourable modifications of lifestyle factors (e.g. physical activity, diet and not smoking) and healthcare (e.g. effective vascular disease prevention) have also increased human life span. Genetic factors contribute to the variation of human life span by around 25%, which is believed to be more profound after 85 years of age. It is likely that multiple factors influence life span and we need answers to questions such as: 1) What does it take to reach 100?, 2) Do centenarians have better health during their lifespan compared with contemporaries who died at a younger age?, 3) Do centenarians have protective modifications of body composition, fat distribution and energy expenditure, maintain high physical and cognitive function, and sustained engagement in social and productive activities?, 4) Do centenarians have genes which contribute to longevity?, 5) Do centenarians benefit from epigenetic phenomena?, 6) Is it possible to influence the transgenerational epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the influence of nutrigenomics important for longevity?, 8) Do centenarians benefit more from drug treatment, particularly in primary prevention?, and, 9) Are there any potential goals for drug research? Many definitions of successful ageing have been proposed, but at present there is no consensus definition. Such definitions may need to differentiate between "Longevity Syndrome" and "Exceptional Longevity".

Genetic variants linked to education predict longevity

PubMed Central

Marioni, Riccardo E.; Ritchie, Stuart J.; Joshi, Peter K.; Hagenaars, Saskia P.; Fischer, Krista; Adams, Mark J.; Hill, W. David; Davies, Gail; Nagy, Reka; Amador, Carmen; Läll, Kristi; Metspalu, Andres; Liewald, David C.; Wilson, James F.; Hayward, Caroline; Esko, Tõnu; Porteous, David J.; Gale, Catharine R.; Deary, Ian J.

2016-01-01

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members’ polygenic profile score for education to predict their parents’ longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths = 79,702) and ∼2.4% lower risk for fathers (total ndeaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity. PMID:27799538

Genetic variants linked to education predict longevity.

PubMed

Marioni, Riccardo E; Ritchie, Stuart J; Joshi, Peter K; Hagenaars, Saskia P; Okbay, Aysu; Fischer, Krista; Adams, Mark J; Hill, W David; Davies, Gail; Nagy, Reka; Amador, Carmen; Läll, Kristi; Metspalu, Andres; Liewald, David C; Campbell, Archie; Wilson, James F; Hayward, Caroline; Esko, Tõnu; Porteous, David J; Gale, Catharine R; Deary, Ian J

2016-11-22

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total n deaths = 79,702) and ∼2.4% lower risk for fathers (total n deaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.

Emotion Regulation Strategies, Secondary Traumatic Stress, and Compassion Satisfaction in Healthcare Providers.

PubMed

Măirean, Cornelia

2016-11-16

The aim of the present study is to examine the relationships between two emotion regulation strategies (cognitive reappraisal and expressive suppression), secondary traumatic stress, and compassion satisfaction in a sample of 190 healthcare providers. Another aim of this study is to examine if the relations between emotion regulation strategies and traumatic stress symptoms are moderated by compassion satisfaction. The respondents volunteered to take part in the research and completed self-reporting measures describing the use of emotional regulation strategies, the symptoms of secondary traumatic stress, and the compassion satisfaction. The results revealed negative associations between cognitive reappraisal and secondary traumatic stress, while expressive suppression is positively associated with arousal. Moreover, cognitive reappraisal is positively related to compassion satisfaction, while secondary traumatic stress symptoms are negatively correlated with compassion satisfaction. Furthermore, the relationship between expressive suppression and intrusions is moderated by compassion satisfaction. The implications of these results for enhancing professional quality of life in the context of secondary exposure to traumatic life events are discussed.

Early and extraordinary peaks in physical performance come with a longevity cost

PubMed Central

van de Vijver, Paul L; van Bodegom, David; Westendorp, Rudi GJ

2016-01-01

Life history theory postulates a trade-off between development and maintenance. This trade-off is observed when comparing life histories of different animal species. In humans, however, it is debated if variation in longevity is explained by differences in developmental traits. Observational studies found a trade-off between early and high fecundity and longevity in women. Development encompasses more than fecundity and also concerns growth and physical performance. Here, we show a life history trade-off between early and above average physical performance and longevity in male Olympic athletes. Athletes who peaked at an earlier age showed 17-percent increased mortality rates (95% CI 8-26% per SD, p<0.001) and athletes who ranked higher showed 11-percent increased mortality rates (95% CI 1-22% per SD, p=0.025). Male athletes who had both an early and extraordinary peak performance suffered a 4.7-year longevity cost. (95% CI 2.1-7.5 years, p=0.001). This is the first time a life history trade-off between physical performance and longevity has been found in humans. This finding deepens our understanding of early developmental influences on the variation of longevity in humans. PMID:27540872

Running as a Key Lifestyle Medicine for Longevity.

PubMed

Lee, Duck-Chul; Brellenthin, Angelique G; Thompson, Paul D; Sui, Xuemei; Lee, I-Min; Lavie, Carl J

Running is a popular and convenient leisure-time physical activity (PA) with a significant impact on longevity. In general, runners have a 25%-40% reduced risk of premature mortality and live approximately 3 years longer than non-runners. Recently, specific questions have emerged regarding the extent of the health benefits of running versus other types of PA, and perhaps more critically, whether there are diminishing returns on health and mortality outcomes with higher amounts of running. This review details the findings surrounding the impact of running on various health outcomes and premature mortality, highlights plausible underlying mechanisms linking running with chronic disease prevention and longevity, identifies the estimated additional life expectancy among runners and other active individuals, and discusses whether there is adequate evidence to suggest that longevity benefits are attenuated with higher doses of running. Copyright © 2017 Elsevier Inc. All rights reserved.

Cooler biologically compatible core body temperatures may prolong longevity and combat neurodegenerative disorders.

PubMed

Salerian, Alen J; Saleri, Nansen G

2006-01-01

Scientific evidence suggests the critical role of temperature in regulating three mechanisms contributing to cellular damage: Oxidative stress, oxygen demand overload and inflammation. In this article, we propose that the Arrhenius rate law has a profound impact on aging and a variety of neurodegenerative disorders including Alzheimer's disease, and we review the supporting evidence. Published studies suggest empirical correlations between temperature and lifespan of various organisms, bolstering the hypothesis that variations in lifespan may stem from differences in the mitochondrial production rates of radicals - a process also influenced by temperature. Given the exponential temperature dependency of all biochemical factors, cooler body temperatures may promote longevity and combat neurodegenerative disorders. This promises to offer extraordinary yet unexplored weapons against two formidable enemies of the human body: aging and neurodegenerative disorders. Stated in the form of a thesis referred to as Salerian and Saleri Temperature Thesis (SSTT): "Cooler biologically compatible core body temperatures prolong lifespan and are of value to combat illness". Double blind studies of SSTT in therapeutic strategies against amyotrophic lateral sclerosis (ALS) or early-stage Alzheimer's disease may offer a reasonable first stage to validate SSTT. In view of the known rapid progressive neurodegeneration associated with ALS, minute variations in core body temperature may, in fact, demonstrate statistically significant differences in disease progression.

[Regulation of heat shock gene expression in response to stress].

PubMed

Garbuz, D G

2017-01-01

Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family. Certain HSFs are activated on exposure to higher temperatures or other adverse factors to ensure stress-induced HS gene expression, while other HSFs are specifically activated at particular developmental stages. The regulation of the main mammalian stress-inducible factor HSF1 and Drosophila melanogaster HSF includes many components, such as a variety of early warning signals indicative of abnormal cell activity (e.g., increases in intracellular ceramide, cytosolic calcium ions, or partly denatured proteins); protein kinases, which phosphorylate HSFs at various Ser residues; acetyltransferases; and regulatory proteins, such as SUMO and HSBP1. Transcription factors other than HSFs are also involved in activating HS gene transcription; the set includes D. melanogaster GAF, mammalian Sp1 and NF-Y, and other factors. Transcription of several stress genes coding for molecular chaperones of the glucose-regulated protein (GRP) family is predominantly regulated by another stress-detecting system, which is known as the unfolded protein response (UPR) system and is activated in response to massive protein misfolding in the endoplasmic reticulum and mitochondrial matrix. A translational fine tuning of HS protein expression occurs via changing the phosphorylation status of several proteins involved in translation initiation. In addition, specific signal sequences in the 5'-UTRs of some HS

The interactive role of eating regulation and stress in the prediction of weight-related outcomes among college students.

PubMed

Arsiwalla, Dilbur D; Arnold, Amanda W; Teel, Karla P; Ulrich, Pamela V; Gropper, Sareen S

2018-02-01

The interactive role of eating regulation and perceived stress on weight-related outcomes was examined among 319 sophomore year college students (110 males and 209 females). Moderated regressions were used to examine interactions between stress and eating regulation on study outcomes including body mass index (BMI) and body fat. Eating regulation moderated associations between stress and BMI and body fat outcomes. Students reporting high perceived stress, high autonomous eating regulation, low controlled regulation, and low amotivation exhibited higher outcomes (BMI and body fat) than those with similar eating regulation but lower perceived stress. Students with lower autonomous eating regulation and higher controlled regulation had no differences in study outcomes across levels of stress. College students who regulate their eating behaviours for health reasons (specifically showing autonomous regulation) exhibit higher BMI and body fat when they report higher levels of perceived stress. Health promotion programs for college students need to target education efforts towards stress reduction and healthy eating behaviours. Copyright © 2017 John Wiley & Sons, Ltd.

Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection.

PubMed

Knops, Paul; Theuns, Dominic A M J; Res, Jan C J; Jordaens, Luc

2009-10-01

Information about implantable cardioverter-defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients. Indications for replacement were classified as a normal end-of-service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single-chamber (SC), dual-chamber (DC), and cardiac resynchronization therapy defibrillator (CRT-D), rate-responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well. In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT-D systems. Longevity was significantly longer in SC systems compared to DC and CRT-D systems (54 +/- 19 vs. 40 +/- 17 and 42 +/- 15 months; P = 0.008). Longevity between non-RR (n = 143) and RR (n = 11) settings was not significantly different (43 +/- 18 vs. 45 +/- 13 months) as it also was not for HO versus non-HO stimulation (43 +/- 19 vs. 46 +/- 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 +/- 19 vs. 44 +/- 18 months). The average longevity on account of a device-based EOS message was 43 +/- 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 +/- 10 months, for ELA Medical (ELA, n = 12) 44 +/- 17 months, for Guidant (GDT, n = 36) 49 +/- 12 months, for Medtronic (MDT, n = 29) 62 +/- 22 months, and for St. Jude Medical (SJM, n = 5) 31 +/- 9 months (P < 0.001). SC ICD generators had a longer service time compared to DC and CRT-D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was

Therapeutic landscapes and longevity: Wellness tourism in Bama.

PubMed

Huang, Liyuan; Xu, Honggang

2018-01-01

Due to the rising demand for healthcare products and concern over environmental pollution, wellness tourism has been booming in China in recent years. The therapeutic landscape theory provides a multi-scale interpretation of wellness tourism to explore how wellness tourists achieve health in healing places. By presenting the results of 83 interviews conducted in Bama, China, this study reveals that the "longevity village" Bama, endorsed by centenarians, provides a retreat that combines natural beauty and a harmonious neighbourhood for wellness tourists. This article argues that although three themes-natural environment, social interaction and symbolic landscape-work together in the healing process of tourists, the symbolic landscape, which is significantly shaped by the longevity culture, plays a dominant role. Longevity in Chinese culture symbolizes the alignment of a strong body, graceful mind, and pleasant habitat. Furthermore, tourism reinforces the importance of symbols and imagination (of a place), the perception of longevity demonstrates the symbolic landscape and thus increases tourists' attachment to the place, and the unusual environment leads to a different therapeutic landscape from that of daily life. Finally, since to date there has been very few works on therapeutic landscapes in China, it is expected that this study will fill the knowledge gap and broaden the scope of application as well as conceptualization of the therapeutic landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human

PubMed Central

Kilic, Ulkan; Gok, Ozlem; Erenberk, Ufuk; Dundaroz, Mehmet Rusen; Torun, Emel; Kucukardali, Yasar; Elibol-Can, Birsen; Uysal, Omer; Dundar, Tolga

2015-01-01

Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene. PMID:25785999

Strong social relationships are associated with decreased longevity in a facultatively social mammal.

PubMed

Blumstein, Daniel T; Williams, Dana M; Lim, Alexandra N; Kroeger, Svenja; Martin, Julien G A

2018-01-31

Humans in strong social relationships are more likely to live longer because social relationships may buffer stressors and thus have protective effects. However, a shortcoming of human studies is that they often rely on self-reporting of these relationships. By contrast, observational studies of non-human animals permit detailed analyses of the specific nature of social relationships. Thus, discoveries that some social animals live longer and healthier lives if they are involved in social grooming, forage together or have more affiliative associates emphasizes the potential importance of social relationships on health and longevity. Previous studies have focused on the impact of social metrics on longevity in obligately social species. However, if sociality indeed has a key role in longevity, we might expect that affiliative relationships should also influence longevity in less social species. We focused on socially flexible yellow-bellied marmots ( Marmota flaviventer ) and asked whether female longevity covaries with the specific nature of social relationships. We quantified social relationships with social network statistics that were based on affiliative interactions, and then estimated the correlation between longevity and sociality using bivariate models. We found a significant negative phenotypic correlation between affiliative social relationship strength and longevity; marmots with greater degree, closeness and those with a greater negative average shortest path length died at younger ages. We conclude that sociality plays an important role in longevity, but how it does so may depend on whether a species is obligately or facultatively social. © 2018 The Author(s).

The Effect of Emotion Regulation Training on Occupational Stress of Critical Care Nurses

PubMed Central

Saedpanah, Darya; Moghaddam, Ladan Fattah

2016-01-01

Introduction Occupational stress is a common, serious and costly health problem in work environment. Nursing is a very stressful job high level of stress in this job affects nurses’ physical and mental health. Aim To investigate the effect of emotion regulation training of occupational stress on critical care nurses in two teaching hospitals in Sanandaj, Iran. Materials and Methods This interventional study was conducted on 60 nurses working in the Intensive Care Unit (ICU) and Critical Care Unit (CCU) in two teaching hospitals in Sanandaj, Iran. Data were collected using Expanded Nursing Stress Scale (ENSS) questionnaire. The questionnaire in both intervention and control groups before and after the training sessions of emotion regulation training were completed. Data were analysed using SPSS Version 20. Statistical indices such as frequency, percentage, mean and standard deviation and also t-test, Chi-square test and paired t-test were used. Results Mean occupation stress score in the intervention group before emotion regulation training was 136.6±24.6 and after training was 113.02±16.2 (p = 0.001). Occupational stress dimensions including; conflict with physicians, problems with peers, workload, uncertainty concerning treatment and problems related to patients and their families in the intervention group compared with the control group was statistically significant (p <0.05). Conclusion Emotion regulation training is effective in reducing occupation stress of critical care nurses. PMID:28208981

Exome-wide Association Study Identifies CLEC3B Missense Variant p.S106G as Being Associated With Extreme Longevity in East Asian Populations

PubMed Central

Tanisawa, Kumpei; Arai, Yasumichi; Hirose, Nobuyoshi; Shimokata, Hiroshi; Yamada, Yoshiji; Kawai, Hisashi; Kojima, Motonaga; Obuchi, Shuichi; Hirano, Hirohiko; Yoshida, Hideyo; Suzuki, Hiroyuki; Fujiwara, Yoshinori; Ihara, Kazushige; Sugaya, Maki; Arai, Tomio; Mori, Seijiro; Sawabe, Motoji; Sato, Noriko; Muramatsu, Masaaki; Higuchi, Mitsuru; Liu, Yao-Wen; Kong, Qing-Peng

2017-01-01

Abstract Life span is a complex trait regulated by multiple genetic and environmental factors; however, the genetic determinants of extreme longevity have been largely unknown. To identify the functional coding variants associated with extreme longevity, we performed an exome-wide association study (EWAS) on a Japanese population by using an Illumina HumanExome Beadchip and a focused replication study on a Chinese population. The EWAS on two independent Japanese cohorts consisting of 530 nonagenarians/centenarians demonstrated that the G allele of CLEC3B missense variant p.S106G was associated with extreme longevity at the exome-wide level of significance (p = 2.33×10–7, odds ratio [OR] = 1.50). The CLEC3B gene encodes tetranectin, a protein implicated in the mineralization process in osteogenesis as well as in the prognosis and metastasis of cancer. The replication study consisting of 448 Chinese nonagenarians/centenarians showed that the G allele of CLEC3B p.S106G was also associated with extreme longevity (p = .027, OR = 1.51), and the p value of this variant reached 1.87×10–8 in the meta-analysis of Japanese and Chinese populations. In conclusion, the present study identified the CLEC3B p.S106G as a novel longevity-associated variant, raising the novel hypothesis that tetranectin, encoded by CLEC3B, plays a role in human longevity and aging. PMID:27154906

Interaction Analysis of Longevity Interventions Using Survival Curves.

PubMed

Nowak, Stefan; Neidhart, Johannes; Szendro, Ivan G; Rzezonka, Jonas; Marathe, Rahul; Krug, Joachim

2018-01-06

A long-standing problem in ageing research is to understand how different factors contributing to longevity should be expected to act in combination under the assumption that they are independent. Standard interaction analysis compares the extension of mean lifespan achieved by a combination of interventions to the prediction under an additive or multiplicative null model, but neither model is fundamentally justified. Moreover, the target of longevity interventions is not mean life span but the entire survival curve. Here we formulate a mathematical approach for predicting the survival curve resulting from a combination of two independent interventions based on the survival curves of the individual treatments, and quantify interaction between interventions as the deviation from this prediction. We test the method on a published data set comprising survival curves for all combinations of four different longevity interventions in Caenorhabditis elegans . We find that interactions are generally weak even when the standard analysis indicates otherwise.

Interaction Analysis of Longevity Interventions Using Survival Curves

PubMed Central

Nowak, Stefan; Neidhart, Johannes; Szendro, Ivan G.; Rzezonka, Jonas; Marathe, Rahul; Krug, Joachim

2018-01-01

A long-standing problem in ageing research is to understand how different factors contributing to longevity should be expected to act in combination under the assumption that they are independent. Standard interaction analysis compares the extension of mean lifespan achieved by a combination of interventions to the prediction under an additive or multiplicative null model, but neither model is fundamentally justified. Moreover, the target of longevity interventions is not mean life span but the entire survival curve. Here we formulate a mathematical approach for predicting the survival curve resulting from a combination of two independent interventions based on the survival curves of the individual treatments, and quantify interaction between interventions as the deviation from this prediction. We test the method on a published data set comprising survival curves for all combinations of four different longevity interventions in Caenorhabditis elegans. We find that interactions are generally weak even when the standard analysis indicates otherwise. PMID:29316622

Autophagy-mediated longevity is modulated by lipoprotein biogenesis

PubMed Central

Seah, Nicole E.; de Magalhaes Filho, C. Daniel; Petrashen, Anna P.; Henderson, Hope R.; Laguer, Jade; Gonzalez, Julissa; Dillin, Andrew; Hansen, Malene; Lapierre, Louis R.

2016-01-01

ABSTRACT Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. PMID:26671266

Work-Family Context and the Longevity Disadvantage of US Women

PubMed Central

Montez, Jennifer Karas; Martikainen, Pekka; Remes, Hanna; Avendano, Mauricio

2015-01-01

Female life expectancy is currently shorter in the United States than in most high-income countries. This study examines work-family context as a potential explanation. While work-family context changed similarly across high-income countries during the past half century, the United States has not implemented institutional supports, such as universally available childcare and family leave, to help Americans contend with these changes. We compare the United States to Finland—a country with similar trends in work-family life but generous institutional supports—and test two hypotheses to explain US women's longevity disadvantage: (1) US women may be less likely than Finnish women to combine employment with childrearing; and (2) US women's longevity may benefit less than Finnish women's longevity from combining employment with childrearing. We used data from women aged 30–60 years during 1988–2006 in the US National Health Interview Survey Linked Mortality File and harmonized it with data from Finnish national registers. We found stronger support for hypothesis 1, especially among low-educated women. Contrary to hypothesis 2, combining employment and childrearing was not less beneficial for US women's longevity. In a simulation exercise, more than 75 percent of US women's longevity disadvantage was eliminated by raising their employment levels to Finnish levels and reducing mortality rates of non-married/non-employed US women to Finnish rates. PMID:27773947

Inequalities of Income and Inequalities of Longevity: A Cross-Country Study

PubMed Central

Plümper, Thomas

2016-01-01

Objectives. We examined the effects of market income inequality (income inequality before taxes and transfers) and income redistribution via taxes and transfers on inequality in longevity. Methods. We used life tables to compute Gini coefficients of longevity inequality for all individuals and for individuals who survived to at least 10 years of age. We regressed longevity inequality on market income inequality and income redistribution, and we controlled for potential confounders, in a cross-sectional time-series sample of up to 28 predominantly Western developed countries and up to 37 years (1974–2011). Results. Income inequality before taxes and transfers was positively associated with inequality in the number of years lived; income redistribution (the difference between market income inequality and income inequality after taxes and transfers were accounted for) was negatively associated with longevity inequality. Conclusions. To the extent that our estimated effects derived from observational data are causal, governments can reduce longevity inequality not only via public health policies, but also via their influence on market income inequality and the redistribution of incomes from the relatively rich to the relatively poor. PMID:26562120

Understanding brassinosteroid-regulated mechanisms to improve stress tolerance in plants: a critical review.

PubMed

Nawaz, Fahim; Naeem, Muhammad; Zulfiqar, Bilal; Akram, Asim; Ashraf, Muhammad Yasin; Raheel, Muhammad; Shabbir, Rana Nauman; Hussain, Rai Altaf; Anwar, Irfan; Aurangzaib, Muhammad

2017-07-01

Brassinosteroids (BRs) are steroidal plant hormones involved in regulation of physiological and molecular processes to ameliorate various biotic and abiotic stresses. Exogenous application of BRs to improve stress tolerance in plants has recently become a high research priority. Several studies have revealed the involvement of these steroidal hormones in upregulation of stress-related defense genes and their cross talk with other metabolic pathways. This is likely to stimulate research on many unanswered questions regarding their role in enhancing the ability of plants to tolerate adverse environmental conditions. Thus, this review appraises new insights on mechanisms mediating BR-regulated changes in plants, focused mainly on their involvement in regulation of physiological and molecular mechanisms under stress conditions. Herein, examples of BR-stimulated modulation of antioxidant defense system and upregulation of transcription factors in plants exposed to various biotic (bacterial, viral, and fungal attack) and abiotic stresses (drought, salinity, heat, low temperature, and heavy metal stress) are discussed. Based on these insights, future research in the current direction can be helpful to increase our understanding of BR-mediated complex and interrelated processes under stress conditions.

Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension?

PubMed

Hans, Harvir; Lone, Asad; Aksenov, Vadim; Rollo, C David

2015-01-01

We examined the impacts of aspirin and metformin on the life history of the cricket Acheta domesticus (growth rate, maturation time, mature body size, survivorship, and maximal longevity). Both drugs significantly increased survivorship and maximal life span. Maximal longevity was 136 days for controls, 188 days (138 % of controls) for metformin, and 194 days (143 % of controls) for aspirin. Metformin and aspirin in combination extended longevity to a lesser degree (163 days, 120 % of controls). Increases in general survivorship were even more pronounced, with low-dose aspirin yielding mean longevity 234 % of controls (i.e., health span). Metformin strongly reduced growth rates of both genders (<60 % of controls), whereas aspirin only slightly reduced the growth rate of females and slightly increased that of males. Both drugs delayed maturation age relative to controls, but metformin had a much greater impact (>140 % of controls) than aspirin (~118 % of controls). Crickets maturing on low aspirin showed no evidence of a trade-off between maturation mass and life extension. Remarkably, by 100 days of age, aspirin-treated females were significantly larger than controls (largely reflecting egg complement). Unlike the reigning dietary restriction paradigm, low aspirin conformed to a paradigm of "eat more, live longer." In contrast, metformin-treated females were only ~67 % of the mass of controls. Our results suggest that hormetic agents like metformin may derive significant trade-offs with life extension, whereas health and longevity benefits may be obtained with less cost by agents like aspirin that regulate geroprotective pathways.

Metabolic engineering of resveratrol and other longevity boosting compounds.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Y; Chen, H; Yu, O

Resveratrol, a compound commonly found in red wine, has attracted many attentions recently. It is a diphenolic natural product accumulated in grapes and a few other species under stress conditions. It possesses a special ability to increase the life span of eukaryotic organisms, ranging from yeast, to fruit fly, to obese mouse. The demand for resveratrol as a food and nutrition supplement has increased significantly in recent years. Extensive work has been carried out to increase the production of resveratrol in plants and microbes. In this review, we will discuss the biosynthetic pathway of resveratrol and engineering methods to heterologouslymore » express the pathway in various organisms. We will outline the shortcuts and limitations of common engineering efforts. We will also discuss briefly the features and engineering challenges of other longevity boosting compounds.« less

28 CFR 345.55 - Longevity pay.

Code of Federal Regulations, 2014 CFR

2014-07-01

... factories or shops. An inmate qualifies for longevity pay raises as provided in the table below: Length of.... An inmate who leaves FPI to enter education, vocational training, or drug abuse treatment programs...

28 CFR 345.55 - Longevity pay.

Code of Federal Regulations, 2010 CFR

2010-07-01

... factories or shops. An inmate qualifies for longevity pay raises as provided in the table below: Length of.... An inmate who leaves FPI to enter education, vocational training, or drug abuse treatment programs...

28 CFR 345.55 - Longevity pay.

Code of Federal Regulations, 2013 CFR

2013-07-01

... factories or shops. An inmate qualifies for longevity pay raises as provided in the table below: Length of.... An inmate who leaves FPI to enter education, vocational training, or drug abuse treatment programs...

28 CFR 345.55 - Longevity pay.

Code of Federal Regulations, 2012 CFR

2012-07-01

... factories or shops. An inmate qualifies for longevity pay raises as provided in the table below: Length of.... An inmate who leaves FPI to enter education, vocational training, or drug abuse treatment programs...

28 CFR 345.55 - Longevity pay.

Code of Federal Regulations, 2011 CFR

2011-07-01

... factories or shops. An inmate qualifies for longevity pay raises as provided in the table below: Length of.... An inmate who leaves FPI to enter education, vocational training, or drug abuse treatment programs...

Is extreme climate or moderate climate more conducive to longevity in China?

NASA Astrophysics Data System (ADS)

Huang, Yi; Rosenberg, Mark; Wang, Yingli

2018-02-01

Climate is closely related to human longevity. In China, there are many climate types. According to national population censuses from 1982 to 2000, most provinces with a high ratio of centenarians are located in western and northwestern China far from the sea; these areas are characterized by a dry, cold climate, very high altitude, very high daily temperature range, strong winds, and partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from 1982 to 2000 are located in southern China near the sea. Previous studies have attributed the high ratio of centenarians in western and northwestern China to the extreme local climate. However, centenarians in these areas decreased greatly in 2010, whereas residents in southern China frequently reached 90 to 100 years old in 2010. This study aims to explain this strange phenomenon and find whether extreme climate in Tibetan plateau and northwestern China or moderate climate in southern China is more conducive to longevity. The study found that mortality rate in Tibetan plateau is much higher than southern China, then a population evolution experiment was proposed to compare longevity indicators between low mortality rate and high mortality rate and shows that longevity indicators will decrease in the near future and increase above their original levels after several decades when the mortality rate is decreased. Results of this study show individuals in northwestern China do not live as long as those in eastern and southern China. A moderate climate is more conducive to longevity than extreme climate in China. The longevity of a region should be judged by long-term longevity indicators.

Is extreme climate or moderate climate more conducive to longevity in China?

NASA Astrophysics Data System (ADS)

Huang, Yi; Rosenberg, Mark; Wang, Yingli

2018-06-01

Climate is closely related to human longevity. In China, there are many climate types. According to national population censuses from 1982 to 2000, most provinces with a high ratio of centenarians are located in western and northwestern China far from the sea; these areas are characterized by a dry, cold climate, very high altitude, very high daily temperature range, strong winds, and partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from 1982 to 2000 are located in southern China near the sea. Previous studies have attributed the high ratio of centenarians in western and northwestern China to the extreme local climate. However, centenarians in these areas decreased greatly in 2010, whereas residents in southern China frequently reached 90 to 100 years old in 2010. This study aims to explain this strange phenomenon and find whether extreme climate in Tibetan plateau and northwestern China or moderate climate in southern China is more conducive to longevity. The study found that mortality rate in Tibetan plateau is much higher than southern China, then a population evolution experiment was proposed to compare longevity indicators between low mortality rate and high mortality rate and shows that longevity indicators will decrease in the near future and increase above their original levels after several decades when the mortality rate is decreased. Results of this study show individuals in northwestern China do not live as long as those in eastern and southern China. A moderate climate is more conducive to longevity than extreme climate in China. The longevity of a region should be judged by long-term longevity indicators.

Adult Literacy Education Program Administrators' Perceptions of Occupational Stress and Coping Mechanisms

ERIC Educational Resources Information Center

Engelmann, Stephanie

2014-01-01

Job performance may be adversely affected by stress. Job stress is a primary contributor to serious physical and emotional health consequences. This quantitative study examined adult literacy program administrator perceptions of occupational stress and coping mechanisms related to job satisfaction, job efficacy, career longevity, and overall…

Parental longevity and offspring's home blood pressure: the Ohasama study.

PubMed

Watanabe, Yumiko; Metoki, Hirohito; Ohkubo, Takayoshi; Hirose, Takuo; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Hara, Azusa; Obara, Taku; Hoshi, Haruhisa; Totsune, Kazuhito; Imai, Yutaka

2010-02-01

Longevity is clustered in particular families. Some studies using conventional blood pressure (BP) reported an association between parental longevity and offspring's BP. No study has used self-measurement of BP at home (home BP). We examined the association between parental longevity and home BP values of adult Japanese offspring. Home and conventional BPs were measured in 1961 residents aged 40 years and over in the general population of Ohasama, Japan. Information about the ages of offspring's parents (age at death or current age) was obtained from a standardized questionnaire. The mean +/- SD values of systolic/diastolic home BP in offspring whose mothers died at less than 69 years of age, at 69-84 years of age, and in offspring whose mothers were alive at age 84 years were 127.4 +/- 13.2/76.2 +/- 9.1, 124.8 +/- 15.0/74.4 +/- 10.0, and 123.4 +/- 15.2/74.4 +/- 10.3 mmHg (P = 0.0002/0.009), respectively. Corresponding values in offspring whose fathers died at less than 66 years of age, at 66-80 years of age, and in offspring whose fathers were alive at age 80 years were 125.7 +/- 15.2/75.6 +/- 10.6, 124.7 +/- 14.1/75.0 +/- 9.2 and 122.4 +/- 14.6/73.6 +/- 9.5 mmHg (P = 0.001/0.003), respectively. Multivariate analysis demonstrated associations that were only weakly observed for conventional BP values (conventional BP: P = 0.3/0.4 for maternal and P = 0.3/0.3 for paternal longevity; home BP: P = 0.05/0.2 for maternal and P = 0.0004/0.007 for paternal longevity). Parental premature death was significantly associated with higher home BP levels in adult offspring, suggesting that parental longevity might be a useful additional marker for screening adult offspring at higher risk of hypertension.

Being cool: how body temperature influences ageing and longevity.

PubMed

Keil, Gerald; Cummings, Elizabeth; de Magalhães, João Pedro

2015-08-01

Temperature is a basic and essential property of any physical system, including living systems. Even modest variations in temperature can have profound effects on organisms, and it has long been thought that as metabolism increases at higher temperatures so should rates of ageing. Here, we review the literature on how temperature affects longevity, ageing and life history traits. From poikilotherms to homeotherms, there is a clear trend for lower temperature being associated with longer lifespans both in wild populations and in laboratory conditions. Many life-extending manipulations in rodents, such as caloric restriction, also decrease core body temperature. Nonetheless, an inverse relationship between temperature and lifespan can be obscured or reversed, especially when the range of body temperatures is small as in homeotherms. An example is observed in humans: women appear to have a slightly higher body temperature and yet live longer than men. The mechanisms involved in the relationship between temperature and longevity also appear to be less direct than once thought with neuroendocrine processes possibly mediating complex physiological responses to temperature changes. Lastly, we discuss species differences in longevity in mammals and how this relates to body temperature and argue that the low temperature of the long-lived naked mole-rat possibly contributes to its exceptional longevity.

STRESS REGULATION AS A LINK BETWEEN EXECUTIVE FUNCTION AND PRE-FRAILTY IN OLDER ADULTS

PubMed Central

Roiland, R.A.; Lin, F.; Phelan, C.; Chapman, B.P.

2017-01-01

Objectives Both pre-frailty and frailty are linked with impaired executive function (EF) but the mechanism underlying this relationship is not known. Williams and colleagues’ model posits EF affects health outcomes via stress regulation. This model was utlized to test indicators of stress regulation as mediators of the relationship between EF and pre-frailty in older adults. Design Cross-sectional. Setting Academic general clinical research centers. Participants 690 community-dwelling older adults ≥ 50 years of age. Measurements Pre-frailty was measured using a modified form of the Fried Frailty measure. EF was assessed via telephone-based neurocognitive assessments. Indicators of stress regulation included: stress exposure (measured by perceived stress), reactivity and recovery (measured by heart rate) and restoration (measured by serum interleukin-6 and sleep quality). Results 396 individuals were classified as non-frail, 277 as pre-frail, and 17 as frail. Pre-frail and non-frail individuals were included in data analyses. Compared to non-frail individuals, prefrail were older and exhibited poorer EF, higher levels of stress exposure and poorer stress restoration. Poorer EF was associated with greater stress exposure, less stress reactivity, longer stress recovery and poorer stress restoration. The total effect of the relationship between EF and pre-frailty was significant with significant indirect effects supporting stress exposure and restoration as mediators of the relationship. Conclusion Stress exposure and restoration appear to mediate the relationship between EF and pre-frailty. Longitudinal studies are needed to clarify the direction of causality and determine whether stress regulation processes are appropriate targets for interventions aiming to prevent declines in EF and the development of pre-frailty. PMID:26412287

The genetics of exceptional longevity: Insights from centenarians.

PubMed

Santos-Lozano, Alejandro; Santamarina, Ana; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Fiuza-Luces, Carmen; Cristi-Montero, Carlos; Bernal-Pino, Aranzazu; Lucia, Alejandro; Garatachea, Nuria

2016-08-01

As the world population ages, so the prevalence increases of individuals aged 100 years or more, known as centenarians. Reaching this age has been described as exceptional longevity (EL) and is attributed to both genetic and environmental factors. Many genetic variations known to affect life expectancy exist in centenarians. This review of studies conducted on centenarians and supercentenarians (older than 110 years) updates knowledge of the impacts on longevity of the twenty most widely investigated single nucleotide polymorphisms (SNPs). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

OxyR Is a Key Regulator in Response to Oxidative Stress in Streptomyces avermitilis.

PubMed

Liu, Xingchao; Sun, Meng; Cheng, Yaqing; Yang, Renjun; Wen, Ying; Chen, Zhi; Li, Jilun

2016-02-02

The role of the H2O2-sensing transcriptional regulator OxyR in oxidative stress responses in Streptomyces avermitilis was investigated. An oxyR deletion mutant was more sensitive to H2O2 and tert-butyl hydroperoxide than was the wild-type strain, indicating that OxyR mediates the defensive system against H2O2 and organic peroxide. Evidence presented herein suggests that in cells treated with exogenous H2O2, the oxidized form of OxyR activated expression of ahpCD by binding to a palindromic sequence of the promoter region. Oxidized OxyR also induced expression of other antioxidant enzymes (KatA1, KatA2, KatA3, OhrB1) and oxidative stress regulators (CatR, OhrR, σR). The thiol-oxidative stress regulator gene sigR was regulated at the transcription level by OxyR. We conclude that OxyR is necessary to activate transcription of sigR from the σR-dependent promoter to express an unstable larger isoform of σR during oxidative stress. In response to oxidative stress, OxyR facilitates rapid production of H2O2-scavenging enzymes to repair oxidative damage through direct regulation and cascaded regulation of CatR, OhrR, and σR.

Influence of internal current and pacing current on pacemaker longevity.

PubMed

Schuchert, A; Kuck, K H

1994-01-01

The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8, 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/- 0.1 microA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.

Improved lipids, diastolic pressure and kidney function are potential contributors to familial longevity: a study on 60 Chinese centenarian families.

PubMed

He, Yong-Han; Pu, Shao-Yan; Xiao, Fu-Hui; Chen, Xiao-Qiong; Yan, Dong-Jing; Liu, Yao-Wen; Lin, Rong; Liao, Xiao-Ping; Yu, Qin; Yang, Li-Qin; Yang, Xing-Li; Ge, Ming-Xia; Li, Ying; Jiang, Jian-Jun; Cai, Wang-Wei; Kong, Qing-Peng

2016-02-25

Centenarians are a good healthy aging model. Interestingly, centenarians' offspring are prone to achieve longevity. Here we recruited 60 longevity families and investigated the blood biochemical indexes of family members to seek candidate factors associated with familial longevity. First, associations of blood indexes with age were tested. Second, associations of blood parameters in centenarians (CEN) with their first generation of offspring (F1) and F1 spouses (F1SP) were analyzed. Third, genes involved in regulating target factors were investigated. We found that total cholesterol (TC) and triglyceride (TG) increased with age (20-80 years), but decreased in CEN. Similarly, blood urea nitrogen (BUN) and blood creatinine (BCr) increased with age (20-80 years), but were maintained on a plateau in CEN. Importantly, we first revealed dual changes in blood pressure, i.e., decreased diastolic blood pressure but increased systolic blood pressure in CEN, which associated with altered CST3 expression. Genetic analysis revealed a significant association of blood uric acid (BUA) and BCr in CEN with F1 but not with F1SP, suggesting they may be heritable traits. Taken together, our results suggest serum lipids, kidney function and especially diastolic pressure rather than systolic pressure were improved in CEN or their offspring, suggesting these factors may play an important role in familial longevity.

Epitranscriptional orchestration of genetic reprogramming is an emergent property of stress-regulated cardiac microRNAs

PubMed Central

Hu, Yuanxin; Matkovich, Scot J.; Hecker, Peter A.; Zhang, Yan; Edwards, John R.; Dorn, Gerald W.

2012-01-01

Cardiac stress responses are driven by an evolutionarily conserved gene expression program comprising dozens of microRNAs and hundreds of mRNAs. Functionalities of different individual microRNAs are being studied, but the overall purpose of interactions between stress-regulated microRNAs and mRNAs and potentially distinct roles for microRNA-mediated epigenetic and conventional transcriptional genetic reprogramming of the stressed heart are unknown. Here we used deep sequencing to interrogate microRNA and mRNA regulation in pressure-overloaded mouse hearts, and performed a genome-wide examination of microRNA–mRNA interactions during early cardiac hypertrophy. Based on abundance and regulatory patterns, cardiac microRNAs were categorized as constitutively expressed housekeeping, regulated homeostatic, or dynamic early stress-responsive microRNAs. Regulation of 62 stress-responsive cardiac microRNAs directly affected levels of only 66 mRNAs, but the global impact of microRNA-mediated epigenetic regulation was amplified by preferential targeting of mRNAs encoding transcription factors, kinases, and phosphatases exerting amplified secondary effects. Thus, an emergent cooperative property of stress-regulated microRNAs is orchestration of transcriptional and posttranslational events that help determine the stress-reactive cardiac phenotype. This global functionality explains how large end-organ effects can be induced through modest individual changes in target mRNA and protein content by microRNAs that sense and respond dynamically to a changing physiological milieu. PMID:23150554

Significant Discrepancy Between Estimated and Actual Longevity in St. Jude Medical Implantable Cardioverter-Defibrillators.

PubMed

Doppalapudi, Harish; Barrios, James; Cuellar, Jose; Gannon, Melanie; Yamada, Takumi; Kumar, Vineet; Maddox, William R; Plumb, Vance J; Brown, Todd M; McElderry, H Tom

2017-05-01

Real-time estimated longevity has been reported in pacemakers for several years, and was recently introduced in implantable cardioverter-defibrillators (ICDs). We sought to evaluate the accuracy of this longevity estimate in St. Jude Medical (SJM) ICDs, especially as the device battery approaches depletion. Among patients with SJM ICDs who underwent generator replacements due to reaching elective replacement indicator (ERI) at our institution, we identified those with devices that provided longevity estimates and reviewed their device interrogations in the 18 months prior to ERI. Significant discrepancy was defined as a difference of more than 12 months between estimated and actual longevity at any point during this period. Forty-six patients with Current/Promote devices formed the study group (40 cardiac resynchronization therapy [CRT] and 6 single/dual chamber). Of these, 34 (74%) had significant discrepancy between estimated and actual longevity (28 CRT and all single/dual). Longevity was significantly overestimated by the device algorithm (mean maximum discrepancy of 18.8 months), more in single/dual than CRT devices (30.5 vs. 17.1 months). Marked discrepancy was seen at voltages ≥2.57 volts, with maximum discrepancy at 2.57 volts (23 months). The overall longevity was higher in the discrepant group of CRT devices than in the nondiscrepant group (67 vs. 61 months, log-rank P = 0.03). There was significant overestimation of longevity in nearly three-fourths of Current/Promote SJM ICDs in the last 18 months prior to ERI. Longevity estimates of SJM ICDs may not be reliable for making clinical decisions on frequency of follow-up, as the battery approaches depletion. © 2017 Wiley Periodicals, Inc.

Is Floral Longevity Influenced by Reproductive Costs and Pollination Success in Cohniella ascendens (Orchidaceae)?

PubMed Central

Abdala-Roberts, Luis; Parra-Tabla, Víctor; Navarro, Jorge

2007-01-01

Background and Aims Although studies have shown that pollen addition and/or removal decreases floral longevity, less attention has been paid to the relationship between reproductive costs and floral longevity. In addition, the influence of reproductive costs on floral longevity responses to pollen addition and/or removal has not yet been evaluated. Here, the orchid Cohniella ascendens is used to answer the following questions. (a) Does experimental removal of flower buds in C. ascendens increase flower longevity? (b) Does pollen addition and/or removal decrease floral longevity, and does this response depend on plant reproductive resource status? Methods To study the effect of reproductive costs on floral longevity 21 plants were selected from which we removed 50 % of the developing flower buds on a marked inflorescence. Another 21 plants were not manipulated (controls). One month later, one of four flowers on each marked inflorescence received one of the following pollen manipulation treatments: control, pollinia removal, pollination without pollinia removal or pollination with pollinia removal. The response variable measured was the number of days each flower remained open (i.e. longevity). Key Results The results showed significant flower bud removal and pollen manipulation effects on floral longevity; the interaction between these two factors was not significant. Flowers on inflorescences with previously removed flower buds remained open significantly longer than flowers on control inflorescences. On the other hand, pollinated flowers closed much faster than control and removed-pollinia flowers, the latter not closing significantly faster than control flowers, although this result was marginal. Conclusions The results emphasize the strong relationship between floral longevity and pollination in orchids, as well as the influence of reproductive costs on the former. PMID:17881335

Is extreme climate or moderate climate more conducive to longevity in China?

PubMed

Huang, Yi; Rosenberg, Mark; Wang, Yingli

2018-06-01

Climate is closely related to human longevity. In China, there are many climate types. According to national population censuses from 1982 to 2000, most provinces with a high ratio of centenarians are located in western and northwestern China far from the sea; these areas are characterized by a dry, cold climate, very high altitude, very high daily temperature range, strong winds, and partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from 1982 to 2000 are located in southern China near the sea. Previous studies have attributed the high ratio of centenarians in western and northwestern China to the extreme local climate. However, centenarians in these areas decreased greatly in 2010, whereas residents in southern China frequently reached 90 to 100 years old in 2010. This study aims to explain this strange phenomenon and find whether extreme climate in Tibetan plateau and northwestern China or moderate climate in southern China is more conducive to longevity. The study found that mortality rate in Tibetan plateau is much higher than southern China, then a population evolution experiment was proposed to compare longevity indicators between low mortality rate and high mortality rate and shows that longevity indicators will decrease in the near future and increase above their original levels after several decades when the mortality rate is decreased. Results of this study show individuals in northwestern China do not live as long as those in eastern and southern China. A moderate climate is more conducive to longevity than extreme climate in China. The longevity of a region should be judged by long-term longevity indicators.

Genetic Signatures of Exceptional Longevity in Humans

PubMed Central

Sebastiani, Paola; Solovieff, Nadia; DeWan, Andrew T.; Walsh, Kyle M.; Puca, Annibale; Hartley, Stephen W.; Melista, Efthymia; Andersen, Stacy; Dworkis, Daniel A.; Wilk, Jemma B.; Myers, Richard H.; Steinberg, Martin H.; Montano, Monty; Baldwin, Clinton T.; Hoh, Josephine; Perls, Thomas T.

2012-01-01

Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity. PMID:22279548

The Role of Stress Regulation on Neural Plasticity in Pain Chronification.

PubMed

Li, Xiaoyun; Hu, Li

2016-01-01

Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications.

The Role of Stress Regulation on Neural Plasticity in Pain Chronification

PubMed Central

Li, Xiaoyun

2016-01-01

Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications. PMID:28053788

Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress.

PubMed

Lee, Samuel; Min Kim, Soo; Dotimas, James; Li, Letitia; Feener, Edward P; Baldus, Stephan; Myers, Ronald B; Chutkow, William A; Patwari, Parth; Yoshioka, Jun; Lee, Richard T

2014-06-01

The endoplasmic reticulum (ER) is responsible for protein folding, modification, and trafficking. Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins that participate in protein folding including protein disulfide isomerases (PDIs). Changes in PDI activity are associated with protein misfolding and ER stress. Here, we show that thioredoxin-interacting protein (Txnip), a member of the arrestin protein superfamily and one of the most strongly induced proteins in diabetic patients, regulates PDI activity and UPR signaling. We found that Txnip binds to PDIs and increases their enzymatic activity. Genetic deletion of Txnip in cells and mice led to increased protein ubiquitination and splicing of the UPR regulated transcription factor X-box-binding protein 1 (Xbp1s) at baseline as well as under ER stress. Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress. © 2014 Brigham and Women's Hospital. Published under the terms of the CC BY 4.0 license.

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

PubMed Central

Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

2014-01-01

Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10–1.69, P = 0.005; OR = 1.20, 95% CI = 1.04–1.37, P = 0.01; OR = 1.27, 95% CI = 1.10–1.46, P = 0.001; OR = 1.14, 95% CI = 1.01–1.27 and OR = 1.24, 95% CI = 1.07–1.43, P = 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33–1.79, P < 0.001; OR = 1.38, 95% CI = 1.15–1.66, P = 0.001; and OR = 1.39, 95% CI = 1.15–1.67, P = 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings. PMID:24589462

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.

PubMed

Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

2014-01-01

Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

Endogenous longevity, biological deterioration and economic growth.

PubMed

Sanso, Marcos; Aísa, Rosa M

2006-05-01

The identification of the types of bidirectional interactions that take place between longevity and economic growth in the long-run is carried out by means of the integration of human capital accumulation, innovation in medical technology, a health goods sector, and individual decisions on health and longevity in a dynamic general equilibrium set-up. In this context, in which individual agents decide not only on their "quality" of life but also on its "quantity", the mere process of biological deterioration, that is to say, the continuous loss of health goods effectiveness in maintaining a given level of health as individuals age, provides the reason for an additional, and new, engine of growth.

Exercise and longevity.

PubMed

Gremeaux, Vincent; Gayda, Mathieu; Lepers, Romuald; Sosner, Philippe; Juneau, Martin; Nigam, Anil

2012-12-01

Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to "successful aging". In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides

PubMed Central

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G.; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V.

2016-01-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans’ life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. PMID:27125673

TAp63 is a master transcriptional regulator of lipid and glucose metabolism

PubMed Central

Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y.; Flores, Elsa R.

2012-01-01

SUMMARY TAp63 prevents premature aging suggesting a link to genes that regulate longevity. Further characterization of TAp63−/− mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance, similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulating energy metabolism by accumulating in response to metabolic stress and transcriptionally activating Sirt1, AMPKα2, and LKB1 resulting in increased fatty acid synthesis and decreased fatty acid oxidation. Moreover, we found that TAp63 lowers blood glucose levels in response to metformin. Restoration of Sirt1, AMPKα2, and LKB1 in TAp63−/− mice rescued some of the metabolic defects of the TAp63−/− mice. Our study defines a role for TAp63 in metabolism and weight control. PMID:23040072

Association of exceptional parental longevity and physical function in aging.

PubMed

Ayers, Emmeline; Barzilai, Nir; Crandall, Jill P; Milman, Sofiya; Verghese, Joe

2014-01-01

Offspring of parents with exceptional longevity (OPEL), who are more likely to carry longevity-associated genotypes, may age more successfully than offspring of parents with usual survival (OPUS). Maintenance of physical function is a key attribute of successful aging. While many genetic and non-genetic factors interact to determine physical phenotype in aging, examination of the contribution of exceptional parental longevity to physical function in aging is limited. The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish (AJ) adults age 65 and older, who were defined as either OPEL (having at least one parent who lived to age 95 or older) or OPUS (neither parent survived to age 95). Subjective and objective measures of physical function were compared between the two groups, accounting for potential confounders. Of the 893 LonGenity subjects, 365 were OPEL and 528 were OPUS. OPEL had better objective and subjective measures of physical function than OPUS, especially on unipedal stance (p = 0.009) and gait speed (p = 0.002). Results support the protective role of exceptional parental longevity in preventing decline in physical function, possibly via genetic mechanisms that should be further explored.

The moderator role of emotion regulation ability in the link between stress and well-being

PubMed Central

Extremera, Natalio; Rey, Lourdes

2015-01-01

This article examined the moderating role of a central core dimension of emotional intelligence—emotion-regulation ability—in the relationship between perceived stress and indicators of well-being (depression and subjective happiness) in a sample from a community adult population. The relationships for males and females on these dimensions were also compared. Results revealed that emotion-regulation abilities moderated both the association between perceived stress and depression/happiness for the total sample. However, a gender-specific analysis showed that the moderation effect was only significant for males. In short, when males reported a high level of perceived stress, those with high scores in regulating emotions reported higher scores in subjective happiness and lower depression symptoms than those with low regulating emotions. However, no interaction effect of regulating emotions and stress for predicting subjective happiness and depression was found for females. In developing stress management programmes for reducing depression and increasing well-being, these findings suggest that training in emotional regulation may be more beneficial for males than females. Our findings are discussed in terms of the need for future research to understand the different gender associations and to consider these differences in further intervention programmes. PMID:26579017

Gut Microbiota and Extreme Longevity.

PubMed

Biagi, Elena; Franceschi, Claudio; Rampelli, Simone; Severgnini, Marco; Ostan, Rita; Turroni, Silvia; Consolandi, Clarissa; Quercia, Sara; Scurti, Maria; Monti, Daniela; Capri, Miriam; Brigidi, Patrizia; Candela, Marco

2016-06-06

The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota of highly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along with age. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae). Copyright © 2016 Elsevier Ltd. All rights reserved.

Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

PubMed

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2016-03-25

The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Parental divorce and adult longevity.

PubMed

Larson, Kandyce; Halfon, Neal

2013-02-01

Life course research has established associations between adverse childhood events and later life health. We examine the relationship of experiencing parental divorce before the age of 16 and survival across 34 years of adulthood. Analysis of panel data from a USA-based survey of 6,928 adults residing in Alameda County, California in 1965. Cox regression was used to examine associations between parental divorce and longevity. Controlling for age, race/ethnicity, gender, and childhood socioeconomic position, respondents who recalled a parental divorce during childhood had increased risk of mortality compared to those with no separation. The association was stronger for premature mortality and deaths due to cardiovascular disease. Divorce in childhood was also associated with lowered adult education, fewer social network ties, more depression, and worse health practices. These factors appeared to explain the association with longevity. Parental divorce in childhood is associated with lowered well-being in adulthood and long-term survival. Early prevention and health promotion efforts may be warranted for children who experience parental divorce or discord as a means of supporting enhanced trajectories of health and well-being.

Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity.

PubMed

Panossian, Alexander; Wikman, Georg

2009-09-01

The aim of this review article is to assess the level of scientific evidence presented by clinical trials of adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong scientific evidence is available for Rhodiola rosea SHR-5 extract, which improved attention, cognitive function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness. Based on their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal preparations that increase tolerance to mental exhaustion and enhance attention and mental endurance in situations of decreased performance. The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stress-activated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their up-regulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly

Plastic Responses Contribute to Explaining Altitudinal and Temporal Variation in Potential Flower Longevity in High Andean Rhodolirion montanum.

PubMed

Pacheco, Diego Andrés; Dudley, Leah S; Cabezas, Josefina; Cavieres, Lohengrin A; Arroyo, Mary T K

2016-01-01

The tendency for flower longevity to increase with altitude is believed by many alpine ecologists to play an important role in compensating for low pollination rates at high altitudes due to cold and variable weather conditions. However, current studies documenting an altitudinal increase in flower longevity in the alpine habitat derive principally from studies on open-pollinated flowers where lower pollinator visitation rates at higher altitudes will tend to lead to flower senescence later in the life-span of a flower in comparison with lower altitudes, and thus could confound the real altitudinal pattern in a species´ potential flower longevity. In a two-year study we tested the hypothesis that a plastic effect of temperature on flower longevity could contribute to an altitudinal increase in potential flower longevity measured in pollinator-excluded flowers in high Andean Rhodolirium montanum Phil. (Amaryllidaceae). Using supplemental warming we investigated whether temperature around flowers plastically affects potential flower longevity. We determined tightly temperature-controlled potential flower longevity and flower height for natural populations on three alpine sites spread over an altitudinal transect from 2350 and 3075 m a.s.l. An experimental increase of 3.1°C around flowers significantly decreased flower longevity indicating a plastic response of flowers to temperature. Flower height in natural populations decreased significantly with altitude. Although temperature negatively affects flower longevity under experimental conditions, we found no evidence that temperature around flowers explains site variation in flower longevity over the altitudinal gradient. In a wetter year, despite a 3.5°C temperature difference around flowers at the extremes of the altitudinal range, flower longevity showed no increase with altitude. However, in a drier year, flower longevity increased significantly with altitude. The emerging picture suggests an increase in flower

Plastic Responses Contribute to Explaining Altitudinal and Temporal Variation in Potential Flower Longevity in High Andean Rhodolirion montanum

PubMed Central

Cavieres, Lohengrin A.

2016-01-01

The tendency for flower longevity to increase with altitude is believed by many alpine ecologists to play an important role in compensating for low pollination rates at high altitudes due to cold and variable weather conditions. However, current studies documenting an altitudinal increase in flower longevity in the alpine habitat derive principally from studies on open-pollinated flowers where lower pollinator visitation rates at higher altitudes will tend to lead to flower senescence later in the life-span of a flower in comparison with lower altitudes, and thus could confound the real altitudinal pattern in a species´ potential flower longevity. In a two-year study we tested the hypothesis that a plastic effect of temperature on flower longevity could contribute to an altitudinal increase in potential flower longevity measured in pollinator-excluded flowers in high Andean Rhodolirium montanum Phil. (Amaryllidaceae). Using supplemental warming we investigated whether temperature around flowers plastically affects potential flower longevity. We determined tightly temperature-controlled potential flower longevity and flower height for natural populations on three alpine sites spread over an altitudinal transect from 2350 and 3075 m a.s.l. An experimental increase of 3.1°C around flowers significantly decreased flower longevity indicating a plastic response of flowers to temperature. Flower height in natural populations decreased significantly with altitude. Although temperature negatively affects flower longevity under experimental conditions, we found no evidence that temperature around flowers explains site variation in flower longevity over the altitudinal gradient. In a wetter year, despite a 3.5°C temperature difference around flowers at the extremes of the altitudinal range, flower longevity showed no increase with altitude. However, in a drier year, flower longevity increased significantly with altitude. The emerging picture suggests an increase in flower

For longevity, perception is everything.

PubMed

Lakhina, Vanisha; Murphy, Coleen T

2015-02-26

Aging is a risk factor for chronic diseases, and identifying targets for intervention is a goal of the aging field. Burkewitz et al. now describe a mechanism that mediates the specific role for AMPK in longevity, whereby its activity in neurons modulates metabolism and mitochondrial integrity in peripheral tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

Study on residual stresses in ultrasonic torsional vibration assisted micro-milling

NASA Astrophysics Data System (ADS)

Lu, Zesheng; Hu, Haijun; Sun, Yazhou; Sun, Qing

2010-10-01

It is well known that machining induced residual stresses can seriously affect the dimensional accuracy, corrosion and wear resistance, etc., and further influence the longevity and reliability of Micro-Optical Components (MOC). In Ultrasonic Torsional Vibration Assisted Micro-milling (UTVAM), cutting parameters, vibration parameters, mill cutter parameters, the status of wear length of tool flank are the main factors which affect residual stresses. A 2D model of UTVAM was established with FE analysis software ABAQUS. Johnson-Cook's flow stress model and shear failure principle are used as the workpiece material model and failure principle, while friction between tool and workpiece uses modified Coulomb's law whose sliding friction area is combined with sticking friction. By means of FEA, the influence rules of cutting parameters, vibration parameters, mill cutter parameters, the status of wear length of tool flank on residual stresses are obtained, which provides a basis for choosing optimal process parameters and improving the longevity and reliability of MOC.

Phenotypic plasticity and longevity in plants and animals: cause and effect?

PubMed

Borges, Renee M

2009-10-01

Immobile plants and immobile modular animals outlive unitary animals. This paper discusses competing but not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of phenotypic plasticity. Stem cell immortality, vascular autonomy, and epicormic branching are some important features of the phenotypic plasticity of plants that contribute to their longevity. Monocarpy versus polycarpy can also influence the kind of senescent processes experienced by plants. How density-dependent phenomena affecting the establishment of juveniles in these immobile organisms can influence the evolution of senescence, and consequently longevity, is reviewed and discussed. Whether climate change scenarios will favour long-lived or short-lived organisms, with their attendant levels of plasticity, is also presented.

Personality and Longevity: Knowns, Unknowns, and Implications for Public Health and Personalized Medicine

PubMed Central

Chapman, Benjamin P.; Roberts, Brent; Duberstein, Paul

2011-01-01

We review evidence for links between personality traits and longevity. We provide an overview of personality for health scientists, using the primary organizing framework used in the study of personality and longevity. We then review data on various aspects of personality linked to longevity. In general, there is good evidence that higher level of conscientiousness and lower levels of hostility and Type D or “distressed” personality are associated with greater longevity. Limited evidence suggests that extraversion, openness, perceived control, and low levels of emotional suppression may be associated with longer lifespan. Findings regarding neuroticism are mixed, supporting the notion that many component(s) of neuroticism detract from life expectancy, but some components at some levels may be healthy or protective. Overall, evidence suggests various personality traits are significant predictors of longevity and points to several promising directions for further study. We conclude by discussing the implications of these links for epidemiologic research and personalized medicine and lay out a translational research agenda for integrating the psychology of individual differences into public health and medicine. PMID:21766032

A retrospective clinical study of cervical restorations: longevity and failure-prognostic variables.

PubMed

Namgung, C; Rho, Y J; Jin, B H; Lim, B S; Cho, B H

2013-01-01

The aim of this retrospective clinical study was to compare the longevity of cervical restorations between resin composite (RC) and glass ionomer (GI) and to investigate variables predictive of their outcome. The clinical performance of the two restorative materials in function was compared using the ratings of the modified United States Public Health Service (USPHS) criteria. A total of 479 cervical restorations were included in the study. Ninety-one already-replaced restorations were reviewed from dental records. The other 388 restorations still in function were evaluated according to the modified USPHS criteria by two investigators. Longevity and prognostic variables were analyzed with the Kaplan-Meier survival analysis and multivariate Cox proportional hazard model. The clinical performances of the two materials were evaluated according to the ratings of the USPHS criteria and compared using the Pearson chi-square test and Fisher exact test. The longevity was not significantly different between RC and GI (median survival time, 10.4 ± 0.7 and 11.5 ± 1.1 years, respectively). The main reasons for failure were loss of retention (82.2%) and secondary caries (17.8%). The longevity of cervical restoration was significantly influenced by tooth group and operator group (Wald test, p<0.05), while material, gender, presence or absence of systemic diseases, arch, and reason for treatment did not affect the longevity. Contrary to the longevity, the clinical performance of RC was superior to GI in the criteria of retention, marginal discoloration, and marginal adaptation, but similar in secondary caries, wear, and postoperative sensitivity.

Lifestyle and nutrition related to male longevity in Sardinia: an ecological study.

PubMed

Pes, G M; Tolu, F; Poulain, M; Errigo, A; Masala, S; Pietrobelli, A; Battistini, N C; Maioli, M

2013-03-01

A demographic analysis in the Mediterranean island of Sardinia revealed marked differences in extreme longevity across the 377 municipalities and particularly identified a mountain inner area where the proportion of oldest subjects among male population has one of the highest validated value worldwide. The cause(s) of this unequal distribution of male longevity may be attributed to a concurrence of environmental, lifestyle and genetic factors. In this study we focussed on some lifestyle and nutrition variables recorded in the island's population in early decades of 20th century, when agricultural and pastoral economy was still prevalent, and try to verify through ecological spatial models if they may account for the variability in male longevity. By computing the Extreme Longevity Index (the proportion of newborns in a given municipality who reach age 100) the island's territory was divided in two areas with relatively higher and lower level of population longevity. Most nutritional variables do not show any significant difference between these two areas whereas a significant difference was found with respect to pastoralism (P = 0.0001), physical activity estimated by the average slope of the territory in each municipality (P = 0.0001), and average daily distance required by the active population to reach the usual workplace (P = 0.0001). Overall, these findings suggest that factors affecting the average energy expenditure of male population such as occupational activity and geographic characteristics of the area where the population mainly resides, are important in explaining the spatial variation of Sardinian extreme longevity. Copyright © 2011 Elsevier B.V. All rights reserved.

Nectarine promotes longevity in Drosophila melanogaster

USDA-ARS?s Scientific Manuscript database

Aging is associated with increased oxidative damage and gradual decline of physiology function with age, and is modulated by numerous genetic and environmental factors. Functional fruits are thought to be ideal candidates for promoting longevity and healthspan due to their high contents of polypheno...

Predictors of Exceptional Longevity: Effects of Early-Life Childhood Conditions, Midlife Environment and Parental Characteristics.

PubMed

Gavrilov, Leonid A; Gavrilova, Natalia S

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890-91 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found that parental longevity and some midlife characteristics proved to be significant predictors of longevity while the role of childhood conditions was less important. More centenarians were born in the second half of the year compared to controls, suggesting early origins of longevity. We found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are the farmer occupation at age 40, Northeastern region of birth in the United States and birth in the second half of year. A gender-specific predictor of female longevity is surprisingly the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880-95. We found that male gender of centenarian has significant positive effect on survival of adult male relatives

Predictors of Exceptional Longevity: Effects of Early-Life Childhood Conditions, Midlife Environment and Parental Characteristics

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2014-01-01

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890–91 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found that parental longevity and some midlife characteristics proved to be significant predictors of longevity while the role of childhood conditions was less important. More centenarians were born in the second half of the year compared to controls, suggesting early origins of longevity. We found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are the farmer occupation at age 40, Northeastern region of birth in the United States and birth in the second half of year. A gender-specific predictor of female longevity is surprisingly the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880–95. We found that male gender of centenarian has significant positive effect on survival of adult male relatives

The genetics of human longevity: an intricacy of genes, environment, culture and microbiome.

PubMed

Dato, Serena; Rose, Giuseppina; Crocco, Paolina; Monti, Daniela; Garagnani, Paolo; Franceschi, Claudio; Passarino, Giuseppe

2017-07-01

Approximately one-quarter of the variation in lifespan in developed countries can be attributed to genetic factors. However, even large population based studies investigating genetic influence on human lifespan have been disappointing, identifying only a few genes accounting for genetic susceptibility to longevity. Some environmental and lifestyle determinants associated with longevity have been identified, which interplay with genetic factors in an intricate way. The study of gene-environment and gene-gene interactions can significantly improve our chance to disentangle this complex scenario. In this review, we first describe the most recent approaches for genetic studies of longevity, from those enriched with health parameters and frailty measures to pathway-based and SNP-SNP interaction analyses. Then, we go deeper into the concept of "environmental influences" in human aging and longevity, focusing on the contribution of life style changes, social and cultural influences, as important determinants of survival differences among individuals in a population. Finally, we discuss the contribution of the microbiome in human longevity, as an example of complex interaction between organism and environment. In conclusion, evidences collected from the latest studies on human longevity provide a support for the collection of life-long genetic and environmental/lifestyle variables with beneficial or detrimental effects on health, to improve our understanding of the determinants of human lifespan. Copyright © 2017 Elsevier B.V. All rights reserved.

Abiotic stress responses in plants: roles of calmodulin-regulated proteins.

PubMed

Virdi, Amardeep S; Singh, Supreet; Singh, Prabhjeet

2015-01-01

Intracellular changes in calcium ions (Ca(2+)) in response to different biotic and abiotic stimuli are detected by various sensor proteins in the plant cell. Calmodulin (CaM) is one of the most extensively studied Ca(2+)-sensing proteins and has been shown to be involved in transduction of Ca(2+) signals. After interacting with Ca(2+), CaM undergoes conformational change and influences the activities of a diverse range of CaM-binding proteins. A number of CaM-binding proteins have also been implicated in stress responses in plants, highlighting the central role played by CaM in adaptation to adverse environmental conditions. Stress adaptation in plants is a highly complex and multigenic response. Identification and characterization of CaM-modulated proteins in relation to different abiotic stresses could, therefore, prove to be essential for a deeper understanding of the molecular mechanisms involved in abiotic stress tolerance in plants. Various studies have revealed involvement of CaM in regulation of metal ions uptake, generation of reactive oxygen species and modulation of transcription factors such as CAMTA3, GTL1, and WRKY39. Activities of several kinases and phosphatases have also been shown to be modulated by CaM, thus providing further versatility to stress-associated signal transduction pathways. The results obtained from contemporary studies are consistent with the proposed role of CaM as an integrator of different stress signaling pathways, which allows plants to maintain homeostasis between different cellular processes. In this review, we have attempted to present the current state of understanding of the role of CaM in modulating different stress-regulated proteins and its implications in augmenting abiotic stress tolerance in plants.

Family Financial Stress and Adolescent Sexual Risk-Taking: The Role of Self-Regulation.

PubMed

Crandall, AliceAnn; Magnusson, Brianna M; Novilla, M Lelinneth B; Novilla, Lynneth Kirsten B; Dyer, W Justin

2017-01-01

The ability to control one's emotions, thoughts, and behaviors is known as self-regulation. Family stress and low adolescent self-regulation have been linked with increased engagement in risky sexual behaviors, which peak in late adolescence and early adulthood. The purpose of this study was to assess whether adolescent self-regulation, measured by parent and adolescent self-report and respiratory sinus arrhythmia, mediates or moderates the relationship between family financial stress and risky sexual behaviors. We assessed these relationships in a 4-year longitudinal sample of 450 adolescents (52 % female; 70 % white) and their parents using structural equation modeling. Results indicated that high family financial stress predicts engagement in risky sexual behaviors as mediated, but not moderated, by adolescent self-regulation. The results suggest that adolescent self-regulatory capacities are a mechanism through which proximal external forces influence adolescent risk-taking. Promoting adolescent self-regulation, especially in the face of external stressors, may be an important method to reduce risk-taking behaviors as adolescents transition to adulthood.

Longevity and ageing: appraising the evolutionary consequences of growing old

PubMed Central

Bonsall, Michael B

2005-01-01

Senescence or ageing is an increase in mortality and/or decline in fertility with increasing age. Evolutionary theories predict that ageing or longevity evolves in response to patterns of extrinsic mortality or intrinsic damage. If ageing is viewed as the outcome of the processes of behaviour, growth and reproduction then it should be possible to predict mortality rate. Recent developments have shown that it is now possible to integrate these ecological and physiological processes and predict the shape of mortality trajectories. By drawing on the key exciting developments in the cellular, physiological and ecological process of longevity the evolutionary consequences of ageing are reviewed. In presenting these ideas an evolutionary demographic framework is used to argue how trade-offs in life-history strategies are important in the maintenance of variation in longevity within and between species. Evolutionary processes associated with longevity have an important role in explaining levels of biological diversity and speciation. In particular, the effects of life-history trait trade-offs in maintaining and promoting species diversity are explored. Such trade-offs can alleviate the effects of intense competition between species and promote species coexistence and diversification. These results have important implications for understanding a number of core ecological processes such as how species are divided among niches, how closely related species co-occur and the rules by which species assemble into food-webs. Theoretical work reveals that the proximate physiological processes are as important as the ecological factors in explaining the variation in the evolution of longevity. Possible future research challenges integrating work on the evolution and mechanisms of growing old are briefly discussed. PMID:16553312

Stress responses at the endometrial-placental interface regulate labyrinthine placental differentiation from trophoblast stem cells.

PubMed

Rappolee, D A; Zhou, S; Puscheck, E E; Xie, Y

2013-05-01

Development can happen in one of two ways. Cells performing a necessary function can differentiate from stem cells before the need for it arises and stress does not develop. Or need arises before function, stress develops and stress signals are part of the normal stimuli that regulate developmental mechanisms. These mechanisms adjust stem cell differentiation to produce function in a timely and proportional manner. In this review, we will interpret data from studies of null lethal mutants for placental stress genes that suggest the latter possibility. Acknowledged stress pathways participate in stress-induced and -regulated differentiation in two ways. These pathways manage the homeostatic response to maintain stem cells during the stress. Stress pathways also direct stem cell differentiation to increase the first essential lineage and suppress later lineages when stem cell accumulation is diminished. This stress-induced differentiation maintains the conceptus during stress. Pathogenic outcomes arise because population sizes of normal stem cells are first depleted by decreased accumulation. The fraction of stem cells is further decreased by differentiation that is induced to compensate for smaller stem cell populations. Analysis of placental lethal null mutant genes known to mediate stress responses suggests that the labyrinthine placenta develops during, and is regulated by, hypoxic stress.

Changes in Teacher Stress through Participation in Pre-Referral Intervention Teams

ERIC Educational Resources Information Center

Lhospital, Ann Shargo; Gregory, Anne

2009-01-01

Teachers today face high stress that can compromise their well-being, longevity in the profession, and the quality of their interactions with students. Pre-referral interventions, which address individual student difficulties before consideration for special education, may help buffer teacher stress through student interventions and team support.…

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides.

PubMed

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V

2016-05-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. © 2016 Artan et al.; Published by Cold Spring Harbor Laboratory Press.

Self-Compassion, Emotion Regulation and Stress among Australian Psychologists: Testing an Emotion Regulation Model of Self-Compassion Using Structural Equation Modeling

PubMed Central

Finlay-Jones, Amy L.; Rees, Clare S.; Kane, Robert T.

2015-01-01

Psychologists tend to report high levels of occupational stress, with serious implications for themselves, their clients, and the discipline as a whole. Recent research suggests that self-compassion is a promising construct for psychologists in terms of its ability to promote psychological wellbeing and resilience to stress; however, the potential benefits of self-compassion are yet to be thoroughly explored amongst this occupational group. Additionally, while a growing body of research supports self-compassion as a key predictor of psychopathology, understanding of the processes by which self-compassion exerts effects on mental health outcomes is limited. Structural equation modelling (SEM) was used to test an emotion regulation model of self-compassion and stress among psychologists, including postgraduate trainees undertaking clinical work (n = 198). Self-compassion significantly negatively predicted emotion regulation difficulties and stress symptoms. Support was also found for our preliminary explanatory model of self-compassion, which demonstrates the mediating role of emotion regulation difficulties in the self-compassion-stress relationship. The final self-compassion model accounted for 26.2% of variance in stress symptoms. Implications of the findings and limitations of the study are discussed. PMID:26207900

Conserved versatile master regulators in signalling pathways in response to stress in plants

PubMed Central

Balderas-Hernández, Victor E.; Alvarado-Rodríguez, Miguel; Fraire-Velázquez, Saúl

2013-01-01

From the first land plants to the complex gymnosperms and angiosperms of today, environmental conditions have forced plants to develop molecular strategies to surpass natural obstacles to growth and proliferation, and these genetic gains have been transmitted to the following generations. In this long natural process, novel and elaborate mechanisms have evolved to enable plants to cope with environmental limitations. Elements in many signalling cascades enable plants to sense different, multiple and simultaneous ambient cues. A group of versatile master regulators of gene expression control plant responses to stressing conditions. For crop breeding purposes, the task is to determine how to activate these key regulators to enable accurate and optimal reactions to common stresses. In this review, we discuss how plants sense biotic and abiotic stresses, how and which master regulators are implied in the responses to these stresses, their evolution in the life kingdoms, and the domains in these proteins that interact with other factors to lead to a proper and efficient plant response. PMID:24147216

76 FR 43604 - Pipeline Safety: Applying Safety Regulations to All Rural Onshore Hazardous Liquid Low-Stress...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-21

... Regulations to All Rural Onshore Hazardous Liquid Low-Stress Lines, Correction AGENCY: Pipeline and Hazardous... the Federal Pipeline Safety Regulations to address rural low-stress hazardous liquid pipelines that... regarding the compliance date for identifying all segments of a Category 3 low-stress pipeline. DATES: This...

The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

PubMed

Walley, Justin W; Rowe, Heather C; Xiao, Yanmei; Chehab, E Wassim; Kliebenstein, Daniel J; Wagner, Doris; Dehesh, Katayoon

2008-12-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

A novel generalized normal distribution for human longevity and other negatively skewed data.

PubMed

Robertson, Henry T; Allison, David B

2012-01-01

Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution.

A Novel Generalized Normal Distribution for Human Longevity and other Negatively Skewed Data

PubMed Central

Robertson, Henry T.; Allison, David B.

2012-01-01

Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution. PMID:22623974

Silicon Regulates Potential Genes Involved in Major Physiological Processes in Plants to Combat Stress

PubMed Central

Manivannan, Abinaya; Ahn, Yul-Kuyn

2017-01-01

Silicon (Si), the quasi-essential element occurs as the second most abundant element in the earth's crust. Biological importance of Si in plant kingdom has become inevitable particularly under stressed environment. In general, plants are classified as high, medium, and low silicon accumulators based on the ability of roots to absorb Si. The uptake of Si directly influence the positive effects attributed to the plant but Si supplementation proves to mitigate stress and recover plant growth even in low accumulating plants like tomato. The application of Si in soil as well as soil-less cultivation systems have resulted in the enhancement of quantitative and qualitative traits of plants even under stressed environment. Silicon possesses several mechanisms to regulate the physiological, biochemical, and antioxidant metabolism in plants to combat abiotic and biotic stresses. Nevertheless, very few reports are available on the aspect of Si-mediated molecular regulation of genes with potential role in stress tolerance. The recent advancements in the era of genomics and transcriptomics have opened an avenue for the determination of molecular rationale associated with the Si amendment to the stress alleviation in plants. Therefore, the present endeavor has attempted to describe the recent discoveries related to the regulation of vital genes involved in photosynthesis, transcription regulation, defense, water transport, polyamine synthesis, and housekeeping genes during abiotic and biotic stress alleviation by Si. Furthermore, an overview of Si-mediated modulation of multiple genes involved in stress response pathways such as phenylpropanoid pathway, jasmonic acid pathway, ABA-dependent or independent regulatory pathway have been discussed in this review. PMID:28824681

The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity.

PubMed

Chaudhari, Snehal N; Kipreos, Edward T

2018-06-14

Fused, elongated mitochondria are more efficient in generating ATP than fragmented mitochondria. In diverse C. elegans longevity pathways, increased levels of fused mitochondria are associated with lifespan extension. Blocking mitochondrial fusion in these animals abolishes their extended longevity. The long-lived C. elegans vhl-1 mutant is an exception that does not have increased fused mitochondria, and is not dependent on fusion for longevity. Loss of mammalian VHL upregulates alternate energy generating pathways. This suggests that mitochondrial fusion facilitates longevity in C. elegans by increasing energy metabolism. In diverse animals, ATP levels broadly decreases with age. Substantial evidence supports the theory that increasing or maintaining energy metabolism promotes the survival of older animals. Increased ATP levels in older animals allow energy-intensive repair and homeostatic mechanisms such as proteostasis that act to prevent cellular aging. These observations support the emerging paradigm that maintaining energy metabolism promotes the survival of older animals. © 2018 WILEY Periodicals, Inc.

Self-Regulation and Economic Stress in Children of Hispanic Immigrants and Their Peers: Better Regulation at a Cost?

ERIC Educational Resources Information Center

McFadyen-Ketchum, Lisa Schlueter; Hurwich-Reiss, Eliana; Stiles, Allison A.; Mendoza, Marina M.; Badanes, Lisa S.; Dmitrieva, Julia; Watamura, Sarah Enos

2016-01-01

Research Findings: Although there is a well-established relationship between economic stress and children's self-regulation, few studies have examined this relationship in children of Hispanic immigrants (COHIs), a rapidly growing population. In a sample of preschool children (N = 165), we examined whether economic stress predicted teacher…

Advanced glycation end-products as markers of aging and longevity in the long-lived Ansell's mole-rat (Fukomys anselli).

PubMed

Dammann, Philip; Sell, David R; Begall, Sabine; Strauch, Christopher; Monnier, Vincent M

2012-06-01

Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell's mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen.

Male reproductive strategy and decreased longevity.

PubMed

Vinogradov, A E

1998-06-01

An explanation of the inter-gender difference in longevity consistent with the 'disposable soma' theory of ageing is proposed. It is based on the concept of r-K selection as applied to the inter-gender situation. The concept predicts that the gender with a higher potential reproductive rate (males) should invest relatively less in somatic maintenance, which in its turn should result in a lower longevity according to the 'disposable soma' theory of ageing. In females, which are interpreted as K-selected organisms, the reproductive strategy strongly depends on steady, secure constitution designed for oocyte/embryo bearing and is therefore closely related to somatic maintenance, whereas in (r-selected) males it has a greater behavioural component--risky, variable, with a greater potential productive success at the expense of somatic maintenance. The higher metabolic and growth rates, a higher premature mortality and a longer period of sexual competence of males also find explanation as a complex of r-selected traits.

Endogenous factors regulating poor-nutrition stress-induced flowering in pharbitis: The involvement of metabolic pathways regulated by aminooxyacetic acid.

PubMed

Koshio, Aya; Hasegawa, Tomomi; Okada, Rieko; Takeno, Kiyotoshi

2015-01-15

The short-day plant pharbitis (also called Japanese morning glory), Ipomoea nil (formerly Pharbitis nil), was induced to flower by poor-nutrition stress. This stress-induced flowering was inhibited by aminooxyacetic acid (AOA), which is a known inhibitor of phenylalanine ammonia-lyase (PAL) and the synthesis of indole-3-acetic acid (IAA) and 1-aminocycropropane-1-carboxylic acid (ACC) and thus regulates endogenous levels of salicylic acid (SA), IAA and polyamine (PA). Stress treatment increased PAL activity in cotyledons, and AOA suppressed this increase. The observed PAL activity and flowering response correlate positively, indicating that AOA functions as a PAL inhibitor. The inhibition of stress-induced flowering by AOA was also overcome by IAA. An antiauxin, 4-chlorophenoxy isobutyric acid, inhibited stress-induced flowering. Both SA and IAA promoted flowering induced by stress. PA also promoted flowering, and the effective PA was found to be putrescine (Put). These results suggest that all of the pathways leading to the synthesis of SA, IAA and Put are responsive to the flowering inhibition by AOA and that these endogenous factors may be involved in the regulation of stress-induced flowering. However, as none of them induced flowering under non-stress conditions, they may function cooperatively to promote flowering. Copyright © 2014 Elsevier GmbH. All rights reserved.

Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study.

PubMed

Anselmi, Chiara Viviani; Malovini, Alberto; Roncarati, Roberta; Novelli, Valeria; Villa, Francesco; Condorelli, Gianluigi; Bellazzi, Riccardo; Puca, Annibale Alessandro

2009-04-01

A number of potential candidate genes in a variety of biological pathways have been associated with longevity in model organisms. Many of these genes have human homologs and thus have the potential to provide insights into human longevity. Recently, several studies suggested that FOXO3A functions as a key bridge for various signaling pathways that influence aging and longevity. Interestingly, Willcox and colleagues identified several variants that displayed significant genotype-gender interaction in male human longevity. In particular, a nested case-control study was performed in an ethnic Japanese population in Hawaii, and five candidate longevity genes were chosen based on links to the insulin-insulin-like growth factor-1 (IGF-1) signaling pathway. In the Willcox study, the investigated genetic variations (rs2802292, rs2764264, and rs13217795) within the FOXO3A gene were significantly associated with longevity in male centenarians. We validated the association of FOXO3A polymorphisms with extreme longevity in males from the Southern Italian Centenarian Study. Particularly, rs2802288, a proxy of rs2802292, showed the best allelic association--minor allele frequency (MAF) = 0.49; p = 0.003; odds ratio (OR) = 1.51; 95% confidence interval (CI), 1.15-1.98). Furthermore, we undertook a meta-analysis to explore the significance of rs2802292 association with longevity by combining the association results of the current study and the findings coming from the Willcox et al. investigation. Our data point to a key role of FOXO3A in human longevity and confirm the feasibility of the identification of such genes with centenarian-controls studies. Moreover, we hypothesize the susceptibility to the longevity phenotype may well be the result of complex interactions involving genes and environmental factors but also gender.

Transcriptome analysis uncovers Arabidopsis F-BOX STRESS INDUCED 1 as a regulator of jasmonic acid and abscisic acid stress gene expression.

PubMed

Gonzalez, Lauren E; Keller, Kristen; Chan, Karen X; Gessel, Megan M; Thines, Bryan C

2017-07-17

The ubiquitin 26S proteasome system (UPS) selectively degrades cellular proteins, which results in physiological changes to eukaryotic cells. F-box proteins are substrate adaptors within the UPS and are responsible for the diversity of potential protein targets. Plant genomes are enriched in F-box genes, but the vast majority of these have unknown roles. This work investigated the Arabidopsis F-box gene F-BOX STRESS INDUCED 1 (FBS1) for its effects on gene expression in order elucidate its previously unknown biological function. Using publically available Affymetrix ATH1 microarray data, we show that FBS1 is significantly co-expressed in abiotic stresses with other well-characterized stress response genes, including important stress-related transcriptional regulators. This gene suite is most highly expressed in roots under cold and salt stresses. Transcriptome analysis of fbs1-1 knock-out plants grown at a chilling temperature shows that hundreds of genes require FBS1 for appropriate expression, and that these genes are enriched in those having roles in both abiotic and biotic stress responses. Based on both this genome-wide expression data set and quantitative real-time PCR (qPCR) analysis, it is apparent that FBS1 is required for elevated expression of many jasmonic acid (JA) genes that have established roles in combatting environmental stresses, and that it also controls a subset of JA biosynthesis genes. FBS1 also significantly impacts abscisic acid (ABA) regulated genes, but this interaction is more complex, as FBS1 has both positive and negative effects on ABA-inducible and ABA-repressible gene modules. One noteworthy effect of FBS1 on ABA-related stress processes, however, is the restraint it imposes on the expression of multiple class I LIPID TRANSFER PROTEIN (LTP) gene family members that have demonstrated protective effects in water deficit-related stresses. FBS1 impacts plant stress responses by regulating hundreds of genes that respond to the plant

Ambient intelligence might support increased longevity.

PubMed

Noury, Norbert

2014-01-01

Several technologies entered our homes to change our lives. First electricity brought light and comfort, now communication technologies are transforming our living place into a connected place allowing new services to be invented, comfort, security, wellness and health services. The ICTs in homes can now help prolonge our longevity.

PML is a ROS sensor activating p53 upon oxidative stress.

PubMed

Niwa-Kawakita, Michiko; Ferhi, Omar; Soilihi, Hassane; Le Bras, Morgane; Lallemand-Breitenbach, Valérie; de Thé, Hugues

2017-11-06

Promyelocytic leukemia (PML) nuclear bodies (NBs) recruit partner proteins, including p53 and its regulators, thereby controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB biogenesis. However, physiological links between PML and oxidative stress response in vivo remain unexplored. Here, we identify PML as a reactive oxygen species (ROS) sensor. Pml -/- cells accumulate ROS, whereas PML expression decreases ROS levels. Unexpectedly, Pml -/- embryos survive acute glutathione depletion. Moreover, Pml -/- animals are resistant to acetaminophen hepatotoxicity or fasting-induced steatosis. Molecularly, Pml -/- animals fail to properly activate oxidative stress-responsive p53 targets, whereas the NRF2 response is amplified and accelerated. Finally, in an oxidative stress-prone background, Pml -/- animals display a longevity phenotype, likely reflecting decreased basal p53 activation. Thus, similar to p53, PML exerts basal antioxidant properties but also drives oxidative stress-induced changes in cell survival/proliferation or metabolism in vivo. Through NB biogenesis, PML therefore couples ROS sensing to p53 responses, shedding a new light on the role of PML in senescence or stem cell biology. © 2017 Niwa-Kawakita et al.

Biogeographic variation in evergreen conifer needle longevity and impacts on boreal forest carbon cycle projections

PubMed Central

Reich, Peter B.; Rich, Roy L.; Lu, Xingjie; Wang, Ying-Ping; Oleksyn, Jacek

2014-01-01

Leaf life span is an important plant trait associated with interspecific variation in leaf, organismal, and ecosystem processes. We hypothesized that intraspecific variation in gymnosperm needle traits with latitude reflects both selection and acclimation for traits adaptive to the associated temperature and moisture gradient. This hypothesis was supported, because across 127 sites along a 2,160-km gradient in North America individuals of Picea glauca, Picea mariana, Pinus banksiana, and Abies balsamea had longer needle life span and lower tissue nitrogen concentration with decreasing mean annual temperature. Similar patterns were noted for Pinus sylvestris across a north–south gradient in Europe. These differences highlight needle longevity as an adaptive feature important to ecological success of boreal conifers across broad climatic ranges. Additionally, differences in leaf life span directly affect annual foliage turnover rate, which along with needle physiology partially regulates carbon cycling through effects on gross primary production and net canopy carbon export. However, most, if not all, global land surface models parameterize needle longevity of boreal evergreen forests as if it were a constant. We incorporated temperature-dependent needle longevity and %nitrogen, and biomass allocation, into a land surface model, Community Atmosphere Biosphere Land Exchange, to assess their impacts on carbon cycling processes. Incorporating realistic parameterization of these variables improved predictions of canopy leaf area index and gross primary production compared with observations from flux sites. Finally, increasingly low foliage turnover and biomass fraction toward the cold far north indicate that a surprisingly small fraction of new biomass is allocated to foliage under such conditions. PMID:25225397

Interaction of Osmotic Stress, Temperature, and Abscisic Acid in the Regulation of Gene Expression in Arabidopsis

PubMed Central

Xiong, Liming; Ishitani, Manabu; Zhu, Jian-Kang

1999-01-01

The impact of simultaneous environmental stresses on plants and how they respond to combined stresses compared with single stresses is largely unclear. By using a transgene (RD29A-LUC) consisting of the firefly luciferase coding sequence (LUC) driven by the stress-responsive RD29A promoter, we investigated the interactive effects of temperature, osmotic stress, and the phytohormone abscisic acid (ABA) in the regulation of gene expression in Arabidopsis seedlings. Results indicated that both positive and negative interactions exist among the studied stress factors in regulating gene expression. At a normal growth temperature (22°C), osmotic stress and ABA act synergistically to induce the transgene expression. Low temperature inhibits the response to osmotic stress or to combined treatment of osmotic stress and ABA, whereas low temperature and ABA treatments are additive in inducing transgene expression. Although high temperature alone does not activate the transgene, it significantly amplifies the effects of ABA and osmotic stress. The effect of multiple stresses in the regulation of RD29A-LUC expression in signal transduction mutants was also studied. The results are discussed in the context of cold and osmotic stress signal transduction pathways. PMID:9880362

Abiotic stress responses in plants: roles of calmodulin-regulated proteins

PubMed Central

Virdi, Amardeep S.; Singh, Supreet; Singh, Prabhjeet

2015-01-01

Intracellular changes in calcium ions (Ca2+) in response to different biotic and abiotic stimuli are detected by various sensor proteins in the plant cell. Calmodulin (CaM) is one of the most extensively studied Ca2+-sensing proteins and has been shown to be involved in transduction of Ca2+ signals. After interacting with Ca2+, CaM undergoes conformational change and influences the activities of a diverse range of CaM-binding proteins. A number of CaM-binding proteins have also been implicated in stress responses in plants, highlighting the central role played by CaM in adaptation to adverse environmental conditions. Stress adaptation in plants is a highly complex and multigenic response. Identification and characterization of CaM-modulated proteins in relation to different abiotic stresses could, therefore, prove to be essential for a deeper understanding of the molecular mechanisms involved in abiotic stress tolerance in plants. Various studies have revealed involvement of CaM in regulation of metal ions uptake, generation of reactive oxygen species and modulation of transcription factors such as CAMTA3, GTL1, and WRKY39. Activities of several kinases and phosphatases have also been shown to be modulated by CaM, thus providing further versatility to stress-associated signal transduction pathways. The results obtained from contemporary studies are consistent with the proposed role of CaM as an integrator of different stress signaling pathways, which allows plants to maintain homeostasis between different cellular processes. In this review, we have attempted to present the current state of understanding of the role of CaM in modulating different stress-regulated proteins and its implications in augmenting abiotic stress tolerance in plants. PMID:26528296

The forkhead-like transcription factor (Fhl1p) maintains yeast replicative lifespan by regulating ribonucleotide reductase 1 (RNR1) gene transcription

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tai, Akiko; Kamei, Yuka; Mukai, Yukio

In eukaryotes, numerous genetic factors contribute to the lifespan including metabolic enzymes, signal transducers, and transcription factors. As previously reported, the forkhead-like transcription factor (FHL1) gene was required for yeast replicative lifespan and cell proliferation. To determine how Fhl1p regulates the lifespan, we performed a DNA microarray analysis of a heterozygous diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which were then screened for lifespan-regulating activity. We identified the ribonucleotide reductase (RNR) 1 gene (RNR1) as a regulator of replicative lifespan. RNR1 encodes a large subunit of the RNR complex, which consists of two large (Rnr1p/Rnr3p) and twomore » small (Rnr2p/Rnr4p) subunits. Heterozygous deletion of FHL1 reduced transcription of RNR1 and RNR3, but not RNR2 and RNR4. Chromatin immunoprecipitation showed that Fhl1p binds to the promoter regions of RNR1 and RNR3. Cells harboring an RNR1 deletion or an rnr1-C428A mutation, which abolishes RNR catalytic activity, exhibited a short lifespan. In contrast, cells with a deletion of the other RNR genes had a normal lifespan. Overexpression of RNR1, but not RNR3, restored the lifespan of the heterozygous FHL1 mutant to the wild-type (WT) level. The Δfhl1/FHL1 mutant conferred a decrease in dNTP levels and an increase in hydroxyurea (HU) sensitivity. These findings reveal that Fhl1p regulates RNR1 gene transcription to maintain dNTP levels, thus modulating longevity by protection against replication stress. - Highlights: • Fhl1p regulates replicative lifespan and transcription of RNR large subunit genes. • Rnr1p uniquely acts as a lifespan regulator independent of the RNR complex. • dNTP levels modulate longevity by protection against replication stress.« less

Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease

PubMed Central

Furmanik, Malgorzata; Shanahan, Catherine M.

2017-01-01

Cardiovascular disease continues to be the leading cause of death in industrialised societies. The idea that the arterial smooth muscle cell (ASMC) plays a key role in regulating many vascular pathologies has been gaining importance, as has the realisation that not enough is known about the pathological cellular mechanisms regulating ASMC function in vascular remodelling. In the past decade endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been recognised as a stress response underlying many physiological and pathological processes in various vascular cell types. Here we summarise what is known about how ER stress signalling regulates phenotypic switching, trans/dedifferentiation and apoptosis of ASMCs and contributes to atherosclerosis, hypertension, aneurysms and vascular calcification.

Genome-wide association study for longevity with whole-genome sequencing in 3 cattle breeds.

PubMed

Zhang, Qianqian; Guldbrandtsen, Bernt; Thomasen, Jørn Rind; Lund, Mogens Sandø; Sahana, Goutam

2016-09-01

Longevity is an important economic trait in dairy production. Improvements in longevity could increase the average number of lactations per cow, thereby affecting the profitability of the dairy cattle industry. Improved longevity for cows reduces the replacement cost of stock and enables animals to achieve the highest production period. Moreover, longevity is an indirect indicator of animal welfare. Using whole-genome sequencing variants in 3 dairy cattle breeds, we carried out an association study and identified 7 genomic regions in Holstein and 5 regions in Red Dairy Cattle that were associated with longevity. Meta-analyses of 3 breeds revealed 2 significant genomic regions, located on chromosomes 6 (META-CHR6-88MB) and 18 (META-CHR18-58MB). META-CHR6-88MB overlaps with 2 known genes: neuropeptide G-protein coupled receptor (NPFFR2; 89,052,210-89,059,348 bp) and vitamin D-binding protein precursor (GC; 88,695,940-88,739,180 bp). The NPFFR2 gene was previously identified as a candidate gene for mastitis resistance. META-CHR18-58MB overlaps with zinc finger protein 717 (ZNF717; 58,130,465-58,141,877 bp) and zinc finger protein 613 (ZNF613; 58,115,782-58,117,110 bp), which have been associated with calving difficulties. Information on longevity-associated genomic regions could be used to find causal genes/variants influencing longevity and exploited to improve the reliability of genomic prediction. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dicarbonyl stress and glyoxalase enzyme system regulation in human skeletal muscle.

PubMed

Mey, Jacob T; Blackburn, Brian K; Miranda, Edwin R; Chaves, Alec B; Briller, Joan; Bonini, Marcelo G; Haus, Jacob M

2018-02-01

Skeletal muscle insulin resistance is a hallmark of Type 2 diabetes (T2DM) and may be exacerbated by protein modifications by methylglyoxal (MG), known as dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2 (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein expression, activity, and regulation remain largely unexplored in skeletal muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase enzyme system in the skeletal muscle of subjects with T2DM (age: 56 ± 5 yr.; BMI: 32 ± 2 kg/m 2 ) compared with lean healthy control subjects (LHC; age: 27 ± 1 yr.; BMI: 22 ± 1 kg/m 2 ). Skeletal muscle biopsies obtained from the vastus lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU·m -2 ·min -1 )-euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress and lower GLO1 protein expression (-78.8%), which inversely correlated with BMI, percent body fat, and HOMA-IR, while positively correlating with clamp-derived glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%), which is a positive regulator of GLO1, while Keap1 protein expression, a negative regulator of GLO1, was elevated (207%). Additionally, insulin stimulation during the clamp had a differential effect on NRF2, Keap1, and MG-modified protein expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle insulin resistance. Whether these phenotypic differences contribute to the development of T2DM warrants further investigation.

Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis.

PubMed

Muntané, Gerard; Farré, Xavier; Antonio Rodríguez, Juan; Pegueroles, Cinta; Hughes, David A; de Magalhães, João Pedro; Gabaldón, Toni; Navarro, Arcadi

2018-05-21

Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan (MLS) across primate species. We used two different approaches. First, we searched for parallel amino acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as Wound Healing, Blood Coagulation and Cardiovascular Disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the Antagonistic Pleiotropy (AP) theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the Phylogenetic Generalized Least Squares (PGLS) we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.

Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

PubMed

Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

2017-10-01

The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Battery longevity in cardiac resynchronization therapy implantable cardioverter defibrillators.

PubMed

Alam, Mian Bilal; Munir, Muhammad Bilal; Rattan, Rohit; Flanigan, Susan; Adelstein, Evan; Jain, Sandeep; Saba, Samir

2014-02-01

Cardiac resynchronization therapy (CRT) implantable cardioverter defibrillators (ICDs) deliver high burden ventricular pacing to heart failure patients, which has a significant effect on battery longevity. The aim of this study was to investigate whether battery longevity is comparable for CRT-ICDs from different manufacturers in a contemporary cohort of patients. All the CRT-ICDs implanted at our institution from 1 January 2008 to 31 December 2010 were included in this analysis. Baseline demographic and clinical data were collected on all patients using the electronic medical record. Detailed device information was collected on all patients from scanned device printouts obtained during routine follow-up. The primary endpoint was device replacement for battery reaching the elective replacement indicator (ERI). A total of 646 patients (age 69 ± 13 years), implanted with CRT-ICDs (Boston Scientific 173, Medtronic 416, and St Jude Medical 57) were included in this analysis. During 2.7 ± 1.5 years follow-up, 113 (17%) devices had reached ERI (Boston scientific 4%, Medtronic 25%, and St Jude Medical 7%, P < 0.001). The 4-year survival rate of device battery was significantly worse for Medtronic devices compared with devices from other manufacturers (94% for Boston scientific, 67% for Medtronic, and 92% for St Jude Medical, P < 0.001). The difference in battery longevity by manufacturer was independent of pacing burden, lead parameters, and burden of ICD therapy. There are significant discrepancies in CRT-ICD battery longevity by manufacturer. These data have important implications on clinical practice and patient outcomes.

TATN-1 Mutations Reveal a Novel Role for Tyrosine as a Metabolic Signal That Influences Developmental Decisions and Longevity in Caenorhabditis elegans

PubMed Central

Ferguson, Annabel A.; Dumas, Kathleen J.; Ritov, Vladimir B.; Matern, Dietrich; Hu, Patrick J.; Fisher, Alfred L.

2013-01-01

Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR) signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people. PMID:24385923

Longevity and Depreciation of Audiovisual Equipment.

ERIC Educational Resources Information Center

Post, Richard

1987-01-01

Describes results of survey of media service directors at public universities in Ohio to determine the expected longevity of audiovisual equipment. Use of the Delphi technique for estimates is explained, results are compared with an earlier survey done in 1977, and use of spreadsheet software to calculate depreciation is discussed. (LRW)

Prolonged longevity of hypopituitary dwarf mice.

PubMed

Bartke, A; Brown-Borg, H; Mattison, J; Kinney, B; Hauck, S; Wright, C

2001-01-01

In two types of mutant dwarf mice, congenital deficiencies in pituitary function are associated with remarkably increased life expectancy. In this review, we will describe the key phenotypic characteristics of these animals, the evidence that they exhibit delayed aging, and the mechanisms that are suspected to account for their prolonged longevity.

Female Superintendents' Longevity: Their Experiences

ERIC Educational Resources Information Center

Sampson, Pauline M.

2018-01-01

This paper describes a qualitative research study of the experiences of Texas female superintendents with longevity. Specifically, five superintendents with tenure of at least six years in one school district were interviewed to hear their voices. Findings show that a strong working relationship with their boards, a solid connection with their…

Mother-Infant Emotion Regulation at Three Months: The Role of Maternal Anxiety, Depression and Parenting Stress.

PubMed

Riva Crugnola, Cristina; Ierardi, Elena; Ferro, Valentino; Gallucci, Marcello; Parodi, Cinzia; Astengo, Marina

While the association between anxiety and postpartum depression is well known, few studies have investigated the relationship between these two states and parenting stress. Furthermore, a number of studies have found that postpartum depression affects mother-infant emotion regulation, but there has been only one study on anxiety and emotion regulation and no studies at all on parenting stress and emotion regulation. Therefore, the primary aim of our study is to identify, in a community sample of 71 mothers, the relationship between maternal depression, anxiety, and parenting stress. The second aim is to examine the relationship between anxiety, postpartum depression, and parenting stress and mother-infant emotion regulation assessed at 3 months. Mother-infant interaction was coded with a modified version of the Infant Caregiver and Engagement Phases (ICEP) using a microanalytic approach. The Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), and Parenting Stress Index-Short Form (PSI-SF) were administered to the mothers to assess depression, anxiety, and parenting stress, respectively. Analysis revealed correlations between anxiety and depression, showing that parenting stress is associated with both states. In a laboratory observation, depression was correlated with both negative maternal states and negative dyadic matches as well as infant positive/mother negative mismatches; anxiety was correlated with both negative maternal states and infant negative states as well as mismatches involving one of the partners having a negative state. Multiple regression analysis showed that anxiety is a greater predictor than depression of less adequate styles of mother-infant emotion regulation. Parenting stress was not shown to predict such regulation. © 2016 S. Karger AG, Basel.

The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

PubMed Central

Walley, Justin W.; Rowe, Heather C.; Xiao, Yanmei; Chehab, E. Wassim; Kliebenstein, Daniel J.; Wagner, Doris; Dehesh, Katayoon

2008-01-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584

Interspecific larval competition between invasive Aedes japonicus and native Aedes triseriatus (Diptera: Culicidae) and adult longevity.

PubMed

Alto, Barry W

2011-03-01

The Asian rock pool mosquito Aedes japonicus (Theobald) inhabits natural and artificial container habitats, some of which are occupied by the native treehole mosquitoAedes triseriatus (Say), a vector of LaCrosse encephalitis virus. A laboratory experiment was used to evaluate the effects of nutrient limitation and interspecific interactions between these species. The goal was to address two related hypotheses. First, interspecific interactions between these species show competitive asymmetry with the invasive mosquito Ae. japonicus being favored over Ae. triseriatus. Second, competitive stress at the larval stage alters adult longevity. There was minimal evidence for competitive asymmetry between these two species. Mosquito and population performance showed clear negative density-dependent effects with similar effects of intra- and interspecific interactions. Only Ae. japonicus development time showed competitive asymmetry over Ae. triseriatus, providing weak support for the first hypothesis. For both species, competition resulted in lower adult longevity compared with low competition, providing support for the second hypothesis. These results suggest both species are similarly affected by intra- and interspecific competition and underscore the importance of the effects of larval competition that continue into adulthood and alter parameters important to transmission of vector-borne diseases.

In Search of Rationality in Human Longevity and Immortality

PubMed Central

Bhar, Gopal C.

2016-01-01

The human body is machine-like, but self-moving, self-regulating, and self-adjusting, governed by willpower and intelligence. Aging of the body is basically a maintenance problem and so it could perhaps be postponed by thorough and frequent maintenance. Aging brings on a cascade of ills and health problems leading to deterioration of physical, mental, emotional, and social dimensions of life. This paper deals with solution of the problem philosophically in the light of Indian scriptures without entering into traditional bioethical issues. With a meaningful reason for existence, life can be extended. Examining the scientific perspectives on aging, some common manipulations for its extension are discussed. These are calorie restriction, vitamin and antioxidant treatment, exercise and hormonal interventions, etc. Finally, the question of longevity is explored through pursuance of eternal value-based activity and spirituality in the tradition of Indian heritage. PMID:28031631

Sperm Parameters: Paradigmatic Index of Good Health and Longevity

PubMed Central

Omu, Alexander E.

2013-01-01

Since the discovery of spermatozoon by Anton van Leeuwenhoek in 1677, there has been an ever increasing understanding of its role in reproduction. Many factors adversely affect sperm quality, including varicocele, accessory gland infection, immunological factors, congenital abnormalities, and iatrogenic systemic and endocrine causes, such as diabetes mellitus, obesity, metabolic syndrome, and smoking. The mechanisms responsible for the association between poor sperm parameters and ill health may include oxidative stress, low-grade inflammation, low testosterone, and low sex-hormone-binding globulin. Oxidative stress in the testicular microenvironment may result in decreased spermatogenesis and sperm DNA damage, loss of sperm motility, and abnormal sperm morphology. Low testosterone caused by advanced age, visceral obesity, and inflammation is associated with the development of cardiovascular disease. Hence, semen analysis has an important role in the routine evaluation of idiopathic male infertility, usually manifested as low sperm counts, impaired sperm motility, or absence of sperm, and remains the most common single diagnostic tool. Several studies have shown an inverse relationship between semen quality and medical disorders. This review elucidates the effect of medical disorders and social habits on sperm quality, the mechanisms that are involved in the impairment of sperm quality, and whether or not sperm quality can be used as an index of good health and longevity in a man. PMID:24051979

A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans

PubMed Central

Chamoli, Manish; Singh, Anupama; Malik, Yasir; Mukhopadhyay, Arnab

2014-01-01

Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful. PMID:24655420

Longevity and Mortality in Down's Syndrome.

ERIC Educational Resources Information Center

Thase, M. E.

1982-01-01

Research on the longevity of Down's Syndrome persons is reviewed, and the life span is noted to have increased, although the overall mortality rate is still five times greater than that for the general population. Statistics on causes of mortality (such as immunological abnormalities, congenital heart disease, and malignancy) are summarized. (CL)

AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

PubMed Central

Zhao, Shanchao; Bao, Jiming; Song, Xianlu

2016-01-01

Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (Cls) were calculated by comparing the minor and major alleles. Results A total of seven articles reporting associations of FOX03A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rsI3217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR =1.36, 95% CI, 1. 10–1.69, P=0.005; OR =1.20, 95% CI, 1.04–1.37, P=0.01; OR =1.27, 95% CI, 1.10–1.46, P=0.001; OR =1.14, 95% CI, 1.01–1.27 and OR =1.24, 95% CI, 1.07–1.43, P=0.003, respectively). Analysis is stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR =1.54, 95% CI, 1.33–1.79, P<0.001; OR =1.38, 95% CI, 1.15–1.66, P=0.001; and OR =1.39, 95% CI, 1.15–1.67, P=0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. Conclusions In conclusion, this meta-analysis indicates a significant association of five FOX03A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

Worming our way to novel drug discovery with the Caenorhabditis elegans proteostasis network, stress response and insulin-signaling pathways.

PubMed

O'Reilly, Linda P; Benson, Joshua A; Cummings, Erin E; Perlmutter, David H; Silverman, Gary A; Pak, Stephen C

2014-09-01

Many human diseases result from a failure of a single protein to achieve the correct folding and tertiary conformation. These so-called 'conformational diseases' involve diverse proteins and distinctive cellular pathologies. They all engage the proteostasis network (PN), to varying degrees in an attempt to mange cellular stress and restore protein homeostasis. The insulin/insulin-like growth factor signaling (IIS) pathway is a master regulator of cellular stress response, which is implicated in regulating components of the PN. This review focuses on novel approaches to target conformational diseases. The authors discuss the evidence supporting the involvement of the IIS pathway in modulating the PN and regulating proteostasis in Caenorhabditis elegans. Furthermore, they review previous PN and IIS drug screens and explore the possibility of using C. elegans for whole organism-based drug discovery for modulators of IIS-proteostasis pathways. An alternative approach to develop individualized therapy for each conformational disease is to modulate the global PN. The involvement of the IIS pathway in regulating longevity and response to a variety of stresses is well documented. Increasing data now provide evidence for the close association between the IIS and the PN pathways. The authors believe that high-throughput screening campaigns, which target the C. elegans IIS pathway, may identify drugs that are efficacious in treating numerous conformational diseases.

Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila

PubMed Central

Xia, Brian; de Belle, Steven

2016-01-01

Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies. PMID:27025190

Role and regulation of autophagy in heat stress responses of tomato plants

PubMed Central

Zhou, Jie; Wang, Jian; Yu, Jing-Quan; Chen, Zhixiang

2014-01-01

As sessile organisms, plants are constantly exposed to a wide spectrum of stress conditions such as high temperature, which causes protein misfolding. Misfolded proteins are highly toxic and must be efficiently removed to reduce cellular proteotoxic stress if restoration of native conformations is unsuccessful. Although selective autophagy is known to function in protein quality control by targeting degradation of misfolded and potentially toxic proteins, its role and regulation in heat stress responses have not been analyzed in crop plants. In the present study, we found that heat stress induced expression of autophagy-related (ATG) genes and accumulation of autophagosomes in tomato plants. Virus-induced gene silencing (VIGS) of tomato ATG5 and ATG7 genes resulted in increased sensitivity of tomato plants to heat stress based on both increased development of heat stress symptoms and compromised photosynthetic parameters of heat-stressed leaf tissues. Silencing of tomato homologs for the selective autophagy receptor NBR1, which targets ubiquitinated protein aggregates, also compromised tomato heat tolerance. To better understand the regulation of heat-induced autophagy, we found that silencing of tomato ATG5, ATG7, or NBR1 compromised heat-induced expression of not only the targeted genes but also other autophagy-related genes. Furthermore, we identified two tomato genes encoding proteins highly homologous to Arabidopsis WRKY33 transcription factor, which has been previously shown to interact physically with an autophagy protein. Silencing of tomato WRKY33 genes compromised tomato heat tolerance and reduced heat-induced ATG gene expression and autophagosome accumulation. Based on these results, we propose that heat-induced autophagy in tomato is subject to cooperative regulation by both WRKY33 and ATG proteins and plays a critical role in tomato heat tolerance, mostly likely through selective removal of heat-induced protein aggregates. PMID:24817875

Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae

PubMed Central

Huard, Sylvain; Morettin, Alan; Fullerton, Morgan D.; Côté, Jocelyn

2017-01-01

Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants. While elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. Further our work suggests that NuA4 regulates acetyl-CoA levels through the Acetyl-CoA carboxylase Acc1. Altogether this work establishes both NuA4 and the metabolite acetyl-CoA as critical signaling pathways regulating the formation of glucose-deprived stress granules. PMID:28231279

Regional Distribution of Longevity Population and Elements in Drinking Water in Jiangjin District, Chongqing City, China.

PubMed

Liu, Yonglin; Yuan, Yuyang; Luo, Kunli

2017-10-25

In order to determine the spatial variation of longevity population and elements contained in the drinking water of longevity region in Jiangjin and investigate the relationship between the elements in drinking water and longevity, population censuses on township level and 98 drinking water samples from Jiangjin District, Chongqing City in West China were collected and analyzed. Population statistics on township level showed that the number of centenarians per 100,000 inhabitants (OC), centenarity index (CI), and number of centenarians per 10,000 over 65-year-old subjects (UC) present obvious geographic distribution properties, generally Central region > Northern region > Southern region (Kruskal-Wallis test, p < 0.05). Moderate hard water (150 mg/L < total hardness (TH) = 156.17 mg/L < 300 mg/L) was mainly found in drinking water from longevity township (OC > 7.5) in Jiangjin District, whereas soft water (75 mg/L < TH = 111.23 mg/L < 150 mg/L) was mostly in non-longevity township (OC < 7.5). The mean concentration of strontium (Sr) (0.73 mg/L) in drinking water from the longevity township was apparently higher than that of non-longevity township (0.44 mg/L) (Mann-Whitney U test, p = 0.019 < 0.05). The concentrations of Ba, Li, Mn, Ni, and Se in drinking water from longevity township were also higher than those of non-longevity township (Mann-Whitney U test, p < 0.05). The research indicates that exercising strict control over the concentrations of TH, Sr, Ba, Li, Mn, Ni, and Se in drinking water might be good for the health and prolong people's life.

FurA contributes to the oxidative stress response regulation of Mycobacterium avium ssp. paratuberculosis

PubMed Central

Eckelt, Elke; Meißner, Thorsten; Meens, Jochen; Laarmann, Kristin; Nerlich, Andreas; Jarek, Michael; Weiss, Siegfried; Gerlach, Gerald-F.; Goethe, Ralph

2015-01-01

The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator. PMID:25705205

FurA contributes to the oxidative stress response regulation of Mycobacterium avium ssp. paratuberculosis.

PubMed

Eckelt, Elke; Meißner, Thorsten; Meens, Jochen; Laarmann, Kristin; Nerlich, Andreas; Jarek, Michael; Weiss, Siegfried; Gerlach, Gerald-F; Goethe, Ralph

2015-01-01

The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator.

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16

PubMed Central

Maruthappu, Thiviyani; Chikh, Anissa; Fell, Benjamin; Delaney, Paul J.; Brooke, Matthew A.; Levet, Clemence; Moncada-Pazos, Angela; Ishida-Yamamoto, Akemi; Blaydon, Diana; Waseem, Ahmad; Leigh, Irene M.; Freeman, Matthew; Kelsell, David P.

2017-01-01

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2−/− mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this ‘stress' keratin is regulated. PMID:28128203

Should visceral fat be reduced to increase longevity?

PubMed

Finelli, Carmine; Sommella, Luigi; Gioia, Saverio; La Sala, Nicolina; Tarantino, Giovanni

2013-09-01

Several epidemiologic studies have implicated visceral fat as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and death. Utilizing novel models of visceral obesity, numerous studies have demonstrated that the relationship between visceral fat and longevity is causal while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. Specific recommended intake levels vary based on a number of factors, including current weight, activity levels, and weight loss goals. It is discussed the need of reducing the visceral fat as a potential treatment strategy to prevent or delay age-related diseases and to increase longevity. Copyright © 2013 Elsevier B.V. All rights reserved.

An Analysis of the Relationship Between Metabolism, Developmental Schedules, and Longevity Using Phylogenetic Independent Contrasts

PubMed Central

de Magalhães, João Pedro; Costa, Joana; Church, George M.

2008-01-01

Comparative studies of aging are often difficult to interpret because of the different factors that tend to correlate with longevity. We used the AnAge database to study these factors, particularly metabolism and developmental schedules, previously associated with longevity in vertebrate species. Our results show that, after correcting for body mass and phylogeny, basal metabolic rate does not correlate with longevity in eutherians or birds, although it negatively correlates with marsupial longevity and time to maturity. We confirm the idea that age at maturity is typically proportional to adult life span, and show that mammals that live longer for their body size, such as bats and primates, also tend to have a longer developmental time for their body size. Lastly, postnatal growth rates were negatively correlated with adult life span in mammals but not in birds. Our work provides a detailed view of factors related to species longevity with implications for how comparative studies of aging are interpreted. PMID:17339640

Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics.

PubMed

Miura, Yuri; Hashii, Noritaka; Ohta, Yuki; Itakura, Yoko; Tsumoto, Hiroki; Suzuki, Junya; Takakura, Daisuke; Abe, Yukiko; Arai, Yasumichi; Toyoda, Masashi; Kawasaki, Nana; Hirose, Nobuyoshi; Endo, Tamao

2018-06-01

Glycosylation is highly susceptible to changes of the physiological conditions, and accordingly, is a potential biomarker associated with several diseases and/or longevity. Semi-supercentenarians (SSCs; older than 105 years) are thought to be a model of human longevity. Thus, we performed glycoproteomics using plasma samples of SSCs, and identified proteins and conjugated N-glycans that are characteristic of extreme human longevity. Plasma proteins from Japanese semi-supercentenarians (SSCs, 106-109 years), aged controls (70-88 years), and young controls (20-38 years) were analysed by using lectin microarrays and liquid chromatography/mass spectrometry (LC/MS). Peak area ratios of glycopeptides to corresponding normalising peptides were subjected to orthogonal projections to latent structures discriminant analysis (OPLS-DA). Furthermore, plasma levels of clinical biomarkers were measured. We found two lectins such as Phaseolus vulgaris, and Erythrina cristagalli (ECA), of which protein binding were characteristically increased in SSCs. Peak area ratios of ECA-enriched glycopeptides were successfully discriminated between SSCs and controls using OPLS-DA, and indicated that tri-antennary and sialylated N-glycans of haptoglobin at Asn207 and Asn211 sites were characterized in SSCs. Sialylated glycans of haptoglobin are a potential biomarker of several diseases, such as hepatocellular carcinoma, liver cirrhosis, and IgA-nephritis. However, the SSCs analysed here did not suffer from these diseases. Tri-antennary and sialylated N-glycans on haptoglobin at the Asn207 and Asn211 sites were abundant in SSCs and characteristic of extreme human longevity. We found abundant glycans in SSCs, which may be associated with human longevity. Copyright © 2018 Elsevier B.V. All rights reserved.

Heat shock protein 83 plays pleiotropic roles in embryogenesis, longevity, and fecundity of the pea aphid Acyrthosiphon pisum.

PubMed

Will, Torsten; Schmidtberg, Henrike; Skaljac, Marisa; Vilcinskas, Andreas

2017-01-01

Heat shock protein 83 (HSP83) is homologous to the chaperone HSP90. It has pleiotropic functions in Drosophila melanogaster, including the control of longevity and fecundity, and facilitates morphological evolution by buffering cryptic deleterious mutations in wild populations. In the pea aphid Acyrthosiphon pisum, HSP83 expression is moderately induced by bacterial infection but upregulated more strongly in response to heat stress and fungal infection. Stress-inducible heat shock proteins are of considerable evolutionary and ecological importance because they are known to buffer environmental variation and to influence fitness under non-optimal conditions. To investigate the functions of HSP83 in viviparous aphids, we used RNA interference to attenuate its expression and studied the impact on complex parameters. The RNA interference (RNAi)-mediated depletion of HSP83 expression in A. pisum reduced both longevity and fecundity, suggesting this chaperone has an evolutionarily conserved function in insects. Surprisingly, HSP83 depletion reduced the number of viviparous offspring while simultaneously increasing the number of premature nymphs developing in the ovaries, suggesting an unexpected role in aphid embryogenesis and eclosion. The present study indicates that reduced HSP83 expression in A. pisum reveals both functional similarities and differences compared with its reported roles in holometabolous insects. Its impact on aphid lifespan, fecundity, and embryogenesis suggests a function that determines their fitness. This could be achieved by targeting different client proteins, recruiting distinct co-chaperones or transposon activation.

Associations of triglyceride levels with longevity and frailty: A Mendelian randomization analysis

PubMed Central

Liu, Zuyun; Burgess, Stephen; Wang, Zhengdong; Deng, Wan; Chu, Xuefeng; Cai, Jian; Zhu, Yinsheng; Shi, Jianming; Xie, Xuejuan; Wang, Yong; Jin, Li; Wang, Xiaofeng

2017-01-01

Observational studies suggest associations of triglyceride levels with longevity and frailty. This study aimed to test whether the associations are causal. We used data from the Rugao Longevity and Ageing Study, a population-based cohort study performed in Rugao, China. A variant in the APOA5 gene region (rs662799) was used as the genetic instrument. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted triglycerides with two ageing phenotypes – longevity ( ≥95 years) and frailty (modified Fried frailty phenotype and Rockwood frailty index). C allele of rs662799 was robustly associated with higher triglyceride levels in the comparison group (β = 0.301 mmol/L per allele, p < 0.001), with an F statistic of 95.3 and R2 = 0.040. However MR analysis did not provide strong evidence for an association between genetically predicted triglyceride levels and probability of longevity (OR: 0.61; 95% CI: 0.35, 1.07 per 1 mmol/L increase in triglycerides). In the ageing arm (70–84 years), genetically predicted triglyceride levels were not associated with the frailty index (β = 0.008; 95% CI: −0.013, 0.029) or the frailty phenotype (OR: 1.91; 95% CI: 0.84, 4.37). In conclusion, there is currently a lack of sufficient evidence to support causal associations of triglyceride levels with longevity and frailty in elderly populations. PMID:28134330

FOXO Transcriptional Factors and Long-Term Living

PubMed Central

Rashid, Rehana; Muneer, Saiqa; Hasan, Syed Muhammad Farid

2017-01-01

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity. PMID:28894507

Dietary regulation of hypodermal polyploidization in C. elegans

PubMed Central

Tain, Luke S; Lozano, Encarnación; Sáez, Alberto G; Leroi, Armand M

2008-01-01

Background Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Results Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. Conclusion We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway. PMID:18366811

Dietary regulation of hypodermal polyploidization in C. elegans.

PubMed

Tain, Luke S; Lozano, Encarnación; Sáez, Alberto G; Leroi, Armand M

2008-03-12

Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway.

78 FR 78694 - Orders: Supplemental Orders on Reporting by Regulated Entities of Stress Testing Results as of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... Reporting by Regulated Entities of Stress Testing Results as of September 30, 2013 AGENCY: Federal Housing... provide to the regulated entities two additional appendices of scenario assumptions to be used for stress... STRESS TESTING RESULTS AS OF SEPTEMBER 30, 2013 Whereas, section 165(i)(2) of the Dodd-Frank Wall Street...

Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans.

PubMed

Wan, Qin-Li; Shi, Xiaohuo; Liu, Jiangxin; Ding, Ai-Jun; Pu, Yuan-Zhu; Li, Zhigang; Wu, Gui-Sheng; Luo, Huai-Rong

2017-02-06

In Caenorhabditis elegans (C. elegans) , ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans . Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans .

Salivary cytokine response in the aftermath of stress: An emotion regulation perspective.

PubMed

Newton, Tamara L; Fernandez-Botran, Rafael; Lyle, Keith B; Szabo, Yvette Z; Miller, James J; Warnecke, Ashlee J

2017-09-01

Elevated inflammation in the context of stress has been implicated in mental and physical health. Approaching this from an emotion regulation perspective, we tested whether the salivary cytokine response to stress is dampened by using distraction to minimize opportunity for poststressor rumination. Healthy young adults were randomized to an acute stressor: modified Trier Social Stress Test (TSST, Study 1) or angry memory retrieval (Study 2). Within each study, participants were randomized to poststressor condition-rest or distraction-at a 3:1 ratio. Saliva, collected before and 40 min after the end of each stressor, was assayed for proinflammatory cytokines (PICs): interleukin-1β (IL-1β), TNF-α, and IL-6. Both stressors increased all PICs, and both provoked negative emotion. At 40 min post-TSST, salivary PIC increases did not differ between distraction and rest, but correlated positively with emotional reactivity to stress. At 40 min after memory retrieval, IL-1β increases and intrusive rumination were lower during distraction than rest, but did not correlate with emotional reactivity. Trait rumination and interference control mechanisms, also measured, played little role in PIC increases. Overall, after some stressors, some salivary cytokine responses are lower during distraction than rest. The roles of specific emotions, emotional intensity, and poststressor timing of saliva collection in this finding require clarification. Furthermore, the possibility of two affective paths to inflammation in the context of stress-one sensitive to opportunities for early occurring emotion regulation (as reflected in emotional reactivity), and one sensitive to late-occurring emotion regulation (as reflected in distraction after stress)-deserves attention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Evolutionary history and stress regulation of plant receptor-like kinase/pelle genes.

PubMed

Lehti-Shiu, Melissa D; Zou, Cheng; Hanada, Kousuke; Shiu, Shin-Han

2009-05-01

Receptor-Like Kinase (RLK)/Pelle genes play roles ranging from growth regulation to defense response, and the dramatic expansion of this family has been postulated to be crucial for plant-specific adaptations. Despite this, little is known about the history of or the factors that contributed to the dramatic expansion of this gene family. In this study, we show that expansion coincided with the establishment of land plants and that RLK/Pelle subfamilies were established early in land plant evolution. The RLK/Pelle family expanded at a significantly higher rate than other kinases, due in large part to expansion of a few subfamilies by tandem duplication. Interestingly, these subfamilies tend to have members with known roles in defense response, suggesting that their rapid expansion was likely a consequence of adaptation to fast-evolving pathogens. Arabidopsis (Arabidopsis thaliana) expression data support the importance of RLK/Pelles in biotic stress response. We found that hundreds of RLK/Pelles are up-regulated by biotic stress. Furthermore, stress responsiveness is correlated with the degree of tandem duplication in RLK/Pelle subfamilies. Our findings suggest a link between stress response and tandem duplication and provide an explanation for why a large proportion of the RLK/Pelle gene family is found in tandem repeats. In addition, our findings provide a useful framework for potentially predicting RLK/Pelle stress functions based on knowledge of expansion pattern and duplication mechanism. Finally, we propose that the detection of highly variable molecular patterns associated with specific pathogens/parasites is the main reason for the up-regulation of hundreds of RLK/Pelles under biotic stress.

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

PubMed

Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

2016-05-24

Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

Social exclusion, personal control, self-regulation, and stress among substance abuse treatment clients.

PubMed

Cole, Jennifer; Logan, T K; Walker, Robert

2011-01-01

The purpose of this study was to examine the relationship of social exclusion, personal control, and self-regulation to perceived stress among individuals who participated in publicly funded substance abuse treatment. Participants entered treatment between June 2006 and July 2007 and completed a 12-month follow-up survey by telephone (n=787). The results of the OLS regression analysis indicate that individuals with greater social exclusion factors (e.g. greater economic hardship, lower subjective social standing, greater perceived discrimination), lower perceived control of one's life, and lower self-regulation had higher perceived stress. Furthermore, a significant interaction was found suggesting a stress-buffering effect of personal control between subjective social standing and perceived stress. Interestingly, income status was not significantly related to perceived stress, while economic hardship, which assesses participants' inability to meet basic expenses, was significantly associated with perceived stress. Future research should examine how to integrate the AA/NA teaching about powerlessness and its role in recovery with the importance of increased personal control and self-control in decreasing perceived stress. Implications for future research and substance abuse treatment are discussed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The rpoE operon regulates heat stress response in Burkholderia pseudomallei.

PubMed

Vanaporn, Muthita; Vattanaviboon, Paiboon; Thongboonkerd, Visith; Korbsrisate, Sunee

2008-07-01

Burkholderia pseudomallei is a gram-negative bacterium and the causative agent of melioidosis, one of the important lethal diseases in tropical regions. In this article, we demonstrate the crucial role of the B. pseudomallei rpoE locus in the response to heat stress. The rpoE operon knockout mutant exhibited growth retardation and reduced survival when exposed to a high temperature. Expression analysis using rpoH promoter-lacZ fusion revealed that heat stress induction of rpoH, which encodes heat shock sigma factor (sigma(H)), was abolished in the B. pseudomallei rpoE mutant. Analysis of the rpoH promoter region revealed sequences sharing high homology to the consensus sequence of sigma(E)-dependent promoters. Moreover, the putative heat-induced sigma(H)-regulated heat shock proteins (i.e. GroEL and HtpG) were also absent in the rpoE operon mutant. Altogether, our data suggest that the rpoE operon regulates B. pseudomallei heat stress response through the function of rpoH.

Engineering of global regulators and cell surface properties toward enhancing stress tolerance in Saccharomyces cerevisiae.

PubMed

Kuroda, Kouichi; Ueda, Mitsuyoshi

2017-12-01

Microbial cell factories are subject to various stresses, leading to the reductions of metabolic activity and bioproduction efficiency. Therefore, the development of stress-tolerant microorganisms is important for improving bio-production efficiency. Recently, modifications of cell surface properties and master regulators have been shown to be effective approaches for enhancing stress tolerance. The cell surface is an attractive target owing to its interactions with the environment and its role in transmitting environmental information. Cell surface engineering in yeast has enabled the convenient modification of cell surface properties. Displaying random peptide libraries and subsequent screening can successfully improve stress tolerance. Furthermore, master regulators including transcription factors are also promising target to be engineered because stress tolerance is determined by many cooperative factors and modification of master regulators can simultaneously affect the expression of multiple downstream genes. The key single amino acid mutations in transcription factors have been identified by analyzing tolerant yeasts that were isolated by adaptive evolution under stress conditions. This enabled the reconstruction of stress-tolerant yeast without burdening cells by introducing the identified mutations. Therefore, for the construction of stress-tolerant yeast from any strains, these two approaches are promising alternatives to conventional overexpression and deletion of stress-related genes. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Antidepressants recruit new neurons to improve stress response regulation

PubMed Central

Surget, A; Tanti, A; Leonardo, E D; Laugeray, A; Rainer, Q; Touma, C; Palme, R; Griebel, G; Ibarguen-Vargas, Y; Hen, R; Belzung, C

2011-01-01

Recent research suggests an involvement of hippocampal neurogenesis in behavioral effects of antidepressants. However, the precise mechanisms through which newborn granule neurons might influence the antidepressant response remain elusive. Here, we demonstrate that unpredictable chronic mild stress in mice not only reduces hippocampal neurogenesis, but also dampens the relationship between hippocampus and the main stress hormone system, the hypothalamo-pituitary-adrenal (HPA) axis. Moreover, this relationship is restored by treatment with the antidepressant fluoxetine, in a neurogenesis-dependent manner. Specifically, chronic stress severely impairs HPA axis activity, the ability of hippocampus to modulate downstream brain areas involved in the stress response, the sensitivity of the hippocampal granule cell network to novelty/glucocorticoid effects and the hippocampus-dependent negative feedback of the HPA axis. Remarkably, we revealed that, although ablation of hippocampal neurogenesis alone does not impair HPA axis activity, the ability of fluoxetine to restore hippocampal regulation of the HPA axis under chronic stress conditions, occurs only in the presence of an intact neurogenic niche. These findings provide a mechanistic framework for understanding how adult-generated new neurons influence the response to antidepressants. We suggest that newly generated neurons may facilitate stress integration and that, during chronic stress or depression, enhancing neurogenesis enables a dysfunctional hippocampus to restore the central control on stress response systems, then allowing recovery. PMID:21537331

Regulation of the corticosteroid signalling system in rainbow trout HPI axis during confinement stress.

PubMed

Kiilerich, Pia; Servili, Arianna; Péron, Sandrine; Valotaire, Claudiane; Goardon, Lionel; Leguen, Isabelle; Prunet, Patrick

2018-03-01

This study aims to shed light on corticosteroid regulation of stress in teleost fish with focus on the corticosteroid signalling system. The role of the mineralocorticoid-like hormone 11-deoxycorticosterone (DOC) in fish is still enigmatic, as is the function of the mineralocorticoid receptor, MR. Low plasma DOC levels and ubiquitous tissue distribution of MR question the physiological relevance of the mineralocorticoid-axis. Furthermore, the particular purpose of each of the three corticosteroid receptors in fish, the glucocorticoid receptors, GR1 and GR2, and the MR, is still largely unknown. Therefore we investigate the regulation of cortisol and DOC in plasma and mRNA levels of MR, GR1 and GR2 in the HPI-axis tissues (hypothalamus, pituitary and interrenal gland) during a detailed confinement stress time-course. Here we show a sustained up-regulation of plasma DOC levels during a confinement stress time-course. However, the low DOC levels compared to cortisol measured in the plasma do not favour an activity of DOC through MR receptors. Furthermore, we show differential contribution of the CRs in regulation and control of HPI axis activity following confinement stress. Judged by the variation of mRNA levels negative feedback regulation of cortisol release occurs on the level of the pituitary via MR and on the level of the interrenal gland via GR2. Finally, asa significant effect of confinement stress on CR expressions was observed in the pituitary gland, we completed this experiment by demonstrating that corticosteroid receptors (GR1, GR2 and MR) are co-expressed in the ACTH cells located in the adenohypophysis. Overall, these data suggest the involvement of these receptors in the regulation of the HPI axis activity by cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

Snag longevity in managed northern hardwoods

Treesearch

Mariko Yamasaki; William B. Leak

2006-01-01

Little information on standing snag and coarse woody debris longevity exists for New England forest types. Forest managers thus lack the information on changes over time of the habitat components influenced by the decay process. We examined the fate of 568 snags that occurred on a long-term hardwood growth study on the Bartlett Experimental Forest, NH. Approximately...

78 FR 59165 - Orders: Information Reporting With Respect to Stress Testing of Regulated Entities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

... Respect to Stress Testing of Regulated Entities AGENCY: Federal Housing Finance Agency. ACTION: Orders... stress tests to determine whether the companies have the capital necessary to absorb losses as a result... stress testing. FHFA anticipates supplementing the rule annually with Orders that provide test scenarios...

Perfectionism related to self-reported insomnia severity, but not when controlled for stress and emotion regulation.

PubMed

Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Pühse, Uwe; Lemola, Sakari; Correll, Christoph U; Cortese, Samuele; Meyer, Till; Holsboer-Trachsler, Edith

2015-01-01

Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account.

Perfectionism related to self-reported insomnia severity, but not when controlled for stress and emotion regulation

PubMed Central

Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Pühse, Uwe; Lemola, Sakari; Correll, Christoph U; Cortese, Samuele; Meyer, Till; Holsboer-Trachsler, Edith

2015-01-01

Background Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Methods Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Results Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. Conclusion Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account. PMID:25678791

Beyond allostatic load: rethinking the role of stress in regulating human development.

PubMed

Ellis, Bruce J; Del Giudice, Marco

2014-02-01

How do exposures to stress affect biobehavioral development and, through it, psychiatric and biomedical disorder? In the health sciences, the allostatic load model provides a widely accepted answer to this question: stress responses, while essential for survival, have negative long-term effects that promote illness. Thus, the benefits of mounting repeated biological responses to threat are traded off against costs to mental and physical health. The adaptive calibration model, an evolutionary-developmental theory of stress-health relations, extends this logic by conceptualizing these trade-offs as decision nodes in allocation of resources. Each decision node influences the next in a chain of resource allocations that become instantiated in the regulatory parameters of stress response systems. Over development, these parameters filter and embed information about key dimensions of environmental stress and support, mediating the organism's openness to environmental inputs, and function to regulate life history strategies to match those dimensions. Drawing on the adaptive calibration model, we propose that consideration of biological fitness trade-offs, as delineated by life history theory, is needed to more fully explain the complex relations between developmental exposures to stress, stress responsivity, behavioral strategies, and health. We conclude that the adaptive calibration model and allostatic load model are only partially complementary and, in some cases, support different approaches to intervention. In the long run, the field may be better served by a model informed by life history theory that addresses the adaptive role of stress response systems in regulating alternative developmental pathways.

Low-Temperature Stress during Capped Brood Stage Increases Pupal Mortality, Misorientation and Adult Mortality in Honey Bees

PubMed Central

Wang, Qing; Xu, Xinjian; Zhu, Xiangjie; Chen, Lin; Zhou, Shujing; Huang, Zachary Y.; Zhou, Bingfeng

2016-01-01

Honey bees (Apis mellifera) are key pollinators, playing a vital role in ecosystem maintenance and stability of crop yields. Recently, reduced honey bee survival has attracted intensive attention. Among all other honey bee stresses, temperature is a fundamental ecological factor that has been shown to affect honey bee survival. Yet, the impact of low temperature stress during capped brood on brood mortality has not been systematically investigated. In addition, little was known about how low temperature exposure during capped brood affects subsequent adult longevity. In this study, capped worker broods at 12 different developmental stages were exposed to 20°C for 12, 24, 36, 48, 60, 72, 84 and 96 hours, followed by incubation at 35°C until emergence. We found that longer durations of low temperature during capped brood led to higher mortality, higher incidences of misorientation inside cells and shorter worker longevity. Capped brood as prepupae and near emergence were more sensitive to low-temperature exposure, while capped larvae and mid-pupal stages showed the highest resistance to low-temperature stress. Our results suggest that prepupae and pupae prior to eclosion are the most sensitive stages to low temperature stress, as they are to other stresses, presumably due to many physiological changes related to metamorphosis happening during these two stages. Understanding how low-temperature stress affects honey bee physiology and longevity can improve honey bee management strategies. PMID:27149383

Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni

PubMed Central

Isokpehi, Raphael D.; Mahmud, Ousman; Mbah, Andreas N.; Simmons, Shaneka S.; Avelar, Lívia; Rajnarayanan, Rajendram V.; Udensi, Udensi K.; Ayensu, Wellington K.; Cohly, Hari H.; Brown, Shyretha D.; Dates, Centdrika R.; Hentz, Sonya D.; Hughes, Shawntae J.; Smith-McInnis, Dominique R.; Patterson, Carvey O.; Sims, Jennifer N.; Turner, Kelisha T.; Williams, Baraka S.; Johnson, Matilda O.; Adubi, Taiwo; Mbuh, Judith V.; Anumudu, Chiaka I.; Adeoye, Grace O.; Thomas, Bolaji N.; Nashiru, Oyekanmi; Oliveira, Guilherme

2011-01-01

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the

Repressors Nrg1 and Nrg2 Regulate a Set of Stress-Responsive Genes in Saccharomyces cerevisiae§

PubMed Central

Vyas, Valmik K.; Berkey, Cristin D.; Miyao, Takenori; Carlson, Marian

2005-01-01

The yeast Saccharomyces cerevisiae responds to environmental stress by rapidly altering the expression of large sets of genes. We report evidence that the transcriptional repressors Nrg1 and Nrg2 (Nrg1/Nrg2), which were previously implicated in glucose repression, regulate a set of stress-responsive genes. Genome-wide expression analysis identified 150 genes that were upregulated in nrg1Δ nrg2Δ double mutant cells, relative to wild-type cells, during growth in glucose. We found that many of these genes are regulated by glucose repression. Stress response elements (STREs) and STRE-like elements are overrepresented in the promoters of these genes, and a search of available expression data sets showed that many are regulated in response to a variety of environmental stress signals. In accord with these findings, mutation of NRG1 and NRG2 enhanced the resistance of cells to salt and oxidative stress and decreased tolerance to freezing. We present evidence that Nrg1/Nrg2 not only contribute to repression of target genes in the absence of stress but also limit induction in response to salt stress. We suggest that Nrg1/Nrg2 fine-tune the regulation of a set of stress-responsive genes. PMID:16278455

Physical nature of longevity of light actinides in dynamic failure phenomenon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uchaev, A. Ya., E-mail: uchaev@expd.vniief.ru; Punin, V. T.; Selchenkova, N. I.

It is shown in this work that the physical nature of the longevity of light actinides under extreme conditions in a range of nonequilibrium states of t ∼ 10{sup –6}–10{sup –10} s is determined by the time needed for the formation of a critical concentration of a cascade of failure centers, which changes connectivity of the body. These centers form a percolation cluster. The longevity is composed of waiting time t{sub w} for the appearance of failure centers and clusterization time t{sub c} of cascade of failure centers, when connectivity in the system of failure centers and the percolation clustermore » arise. A unique mechanism of the dynamic failure process, a unique order parameter, and an equal dimensionality of the space in which the process occurs determine the physical nature of the longevity of metals, including fissionable materials.« less

Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans

PubMed Central

Petrie, Michael A.; Kimball, Amy L.; McHenry, Colleen L.; Suneja, Manish; Yen, Chu-Ling; Sharma, Arpit; Shields, Richard K.

2016-01-01

Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. Purpose: The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Methods: Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. Results: We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p < 0.05); while vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat stress repressed PGC-1α (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05). Conclusion: These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative

Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

PubMed

Petrie, Michael A; Kimball, Amy L; McHenry, Colleen L; Suneja, Manish; Yen, Chu-Ling; Sharma, Arpit; Shields, Richard K

2016-01-01

Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p < 0.05); while vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat stress repressed PGC-1α (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05). These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell

Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity.

PubMed

Ewald, Collin Y; Landis, Jess N; Porter Abate, Jess; Murphy, Coleen T; Blackwell, T Keith

2015-03-05

Interventions that delay ageing mobilize mechanisms that protect and repair cellular components, but it is unknown how these interventions might slow the functional decline of extracellular matrices, which are also damaged during ageing. Reduced insulin/IGF-1 signalling (rIIS) extends lifespan across the evolutionary spectrum, and in juvenile Caenorhabditis elegans also allows the transcription factor DAF-16/FOXO to induce development into dauer, a diapause that withstands harsh conditions. It has been suggested that rIIS delays C. elegans ageing through activation of dauer-related processes during adulthood, but some rIIS conditions confer robust lifespan extension unaccompanied by any dauer-like traits. Here we show that rIIS can promote C. elegans longevity through a program that is genetically distinct from the dauer pathway, and requires the Nrf (NF-E2-related factor) orthologue SKN-1 acting in parallel to DAF-16. SKN-1 is inhibited by IIS and has been broadly implicated in longevity, but is rendered dispensable for rIIS lifespan extension by even mild activity of dauer-related processes. When IIS is decreased under conditions that do not induce dauer traits, SKN-1 most prominently increases expression of collagens and other extracellular matrix genes. Diverse genetic, nutritional, and pharmacological pro-longevity interventions delay an age-related decline in collagen expression. These collagens mediate adulthood extracellular matrix remodelling, and are needed for ageing to be delayed by interventions that do not involve dauer traits. By genetically delineating a dauer-independent rIIS ageing pathway, our results show that IIS controls a broad set of protective mechanisms during C. elegans adulthood, and may facilitate elucidation of processes of general importance for longevity. The importance of collagen production in diverse anti-ageing interventions implies that extracellular matrix remodelling is a generally essential signature of longevity assurance

Health Status and Health Dynamics in an Empirical Model of Expected Longevity*

PubMed Central

Benítez-Silva, Hugo; Ni, Huan

2010-01-01

Expected longevity is an important factor influencing older individuals’ decisions such as consumption, savings, purchase of life insurance and annuities, claiming of Social Security benefits, and labor supply. It has also been shown to be a good predictor of actual longevity, which in turn is highly correlated with health status. A relatively new literature on health investments under uncertainty, which builds upon the seminal work by Grossman (1972), has directly linked longevity with characteristics, behaviors, and decisions by utility maximizing agents. Our empirical model can be understood within that theoretical framework as estimating a production function of longevity. Using longitudinal data from the Health and Retirement Study, we directly incorporate health dynamics in explaining the variation in expected longevities, and compare two alternative measures of health dynamics: the self-reported health change, and the computed health change based on self-reports of health status. In 38% of the reports in our sample, computed health changes are inconsistent with the direct report on health changes over time. And another 15% of the sample can suffer from information losses if computed changes are used to assess changes in actual health. These potentially serious problems raise doubts regarding the use and interpretation of the computed health changes and even the lagged measures of self-reported health as controls for health dynamics in a variety of empirical settings. Our empirical results, controlling for both subjective and objective measures of health status and unobserved heterogeneity in reporting, suggest that self-reported health changes are a preferred measure of health dynamics. PMID:18187217

Longevity candidate genes and their association with personality traits in the elderly

PubMed Central

Luciano, Michelle; Lopez, Lorna M.; de Moor, Marleen H.M.; Harris, Sarah E.; Davies, Gail; Nutile, Teresa; Krueger, Robert F.; Esko, Tõnu; Schlessinger, David; Toshiko, Tanaka; Derringer, Jaime L.; Realo, Anu; Hansell, Narelle K.; Pergadia, Michele L.; Pesonen, Anu-Katriina; Sanna, Serena; Terracciano, Antonio; Madden, Pamela A.F.; Penninx, Brenda; Spinhoven, Philip; Hartman, Catherine; Oostra, Ben A.; Janssens, A. Cecile J.W.; Eriksson, Johan G; Starr, John M.; Cannas, Alessandra; Ferrucci, Luigi; Metspalu, Andres; Wright, Margeret J.; Heath, Andrew C.; van Duijn, Cornelia M.; Bierut, Laura J.; Raikkonen, Katri; Martin, Nicholas G.; Ciullo, Marina; Rujescu, Dan; Boomsma, Dorret I.; Deary, Ian J.

2013-01-01

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI and IPIP inventories) plus related mood states of anxiety and depression. Seventy single nucleotide polymorphisms (SNPs) in six brain expressed, longevity candidate genes (AFG3L2, FRAP1, MAT1A, MAT2A, SYNJ1 and SYNJ2) were typed in over one thousand 70-year old participants from the Lothian Birth Cohort of 1936 (LBC1936). No SNPs were associated with the personality and psychological distress traits at a Bonferroni corrected level of significance (p < 0.0002), but there was an over-representation of nominally significant (p < 0.05) SNPs in the synaptojanin-2 (SYNJ2) gene associated with agreeableness and symptoms of depression. Eight SNPs which showed nominally significant association across personality measurement instruments were tested in an extremely large replication sample of 17 106 participants. SNP rs350292, in SYNJ2, was significant: the minor allele was associated with an average decrease in NEO agreeableness scale scores of 0.25 points, and 0.67 points in the restricted analysis of elderly cohorts (most aged > 60 years). Because we selected a specific set of longevity genes based on functional genomics findings, further research on other longevity gene candidates is warranted to discover whether they are relevant candidates for personality and psychological distress traits. PMID:22213687

Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast.

PubMed

Timón-Gómez, Alba; Proft, Markus; Pascual-Ahuir, Amparo

2013-01-01

Mpc proteins are highly conserved from yeast to humans and are necessary for the uptake of pyruvate at the inner mitochondrial membrane, which is used for leucine and valine biosynthesis and as a fuel for respiration. Our analysis of the yeast MPC gene family suggests that amino acid biosynthesis, respiration rate and oxidative stress tolerance are regulated by changes in the Mpc protein composition of the mitochondria. Mpc2 and Mpc3 are highly similar but functionally different: Mpc2 is most abundant under fermentative non stress conditions and important for amino acid biosynthesis, while Mpc3 is the most abundant family member upon salt stress or when high respiration rates are required. Accordingly, expression of the MPC3 gene is highly activated upon NaCl stress or during the transition from fermentation to respiration, both types of regulation depend on the Hog1 MAP kinase. Overexpression experiments show that gain of Mpc2 function leads to a severe respiration defect and ROS accumulation, while Mpc3 stimulates respiration and enhances tolerance to oxidative stress. Our results identify the regulated mitochondrial pyruvate uptake as an important determinant of respiration rate and stress resistance.

Extreme Longevity in Proteinaceous Deep-Sea Corals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roark, E B; Guilderson, T P; Dunbar, R B

2009-02-09

Deep-sea corals are found on hard substrates on seamounts and continental margins world-wide at depths of 300 to {approx}3000 meters. Deep-sea coral communities are hotspots of deep ocean biomass and biodiversity, providing critical habitat for fish and invertebrates. Newly applied radiocarbon age date from the deep water proteinaceous corals Gerardia sp. and Leiopathes glaberrima show that radial growth rates are as low as 4 to 35 {micro}m yr{sup -1} and that individual colony longevities are on the order of thousands of years. The management and conservation of deep sea coral communities is challenged by their commercial harvest for the jewelrymore » trade and damage caused by deep water fishing practices. In light of their unusual longevity, a better understanding of deep sea coral ecology and their interrelationships with associated benthic communities is needed to inform coherent international conservation strategies for these important deep-sea ecosystems.« less

Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

USDA-ARS?s Scientific Manuscript database

Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

Central roles of iron in the regulation of oxidative stress in the yeast Saccharomyces cerevisiae.

PubMed

Matsuo, Ryo; Mizobuchi, Shogo; Nakashima, Maya; Miki, Kensuke; Ayusawa, Dai; Fujii, Michihiko

2017-10-01

Oxygen is essential for aerobic organisms but causes cytotoxicity probably through the generation of reactive oxygen species (ROS). In this study, we screened for the genes that regulate oxidative stress in the yeast Saccharomyces cerevisiae, and found that expression of CTH2/TIS11 caused an increased resistance to ROS. CTH2 is up-regulated upon iron starvation and functions to remodel metabolism to adapt to iron starvation. We showed here that increased resistance to ROS by CTH2 would likely be caused by the decreased ROS production due to the decreased activity of mitochondrial respiration, which observation is consistent with the fact that CTH2 down-regulates the mitochondrial respiratory proteins. We also found that expression of CTH1, a paralog of CTH2, also caused an increased resistance to ROS. This finding supported the above view, because mitochondrial respiratory proteins are the common targets of CTH1 and CTH2. We further showed that supplementation of iron in medium augmented the growth of S. cerevisiae under oxidative stress, and expression of CTH2 and supplementation of iron collectively enhanced its growth under oxidative stress. Since CTH2 is regulated by iron, these findings suggested that iron played crucial roles in the regulation of oxidative stress in S. cerevisiae.

Effects of several environmental factors on longevity and health of the human population of Zhongxiang, Hubei, China.

PubMed

Lv, Jinmei; Wang, Wuyi; Krafft, Thomas; Li, Yonghua; Zhang, Fengying; Yuan, Fuqing

2011-11-01

Increasing human health and longevity is of global interest. Environmental, genetic, and stochastic factors all affect longevity. Among these factors, the environment is extremely important. To investigate the relationship between the environment and longevity, we studied the environment in Zhongxiang (China), where the inhabitants commonly have long life spans. Air was analyzed for negative oxygen ions, SO2, and inhalable particles, while drinking water and rice were analyzed for macro- and micro-elements. The air quality in this area was determined to be grade I with high negative oxygen ion content and low SO2 and inhalable particle contents. Apart from Fe, Mn, and F, all tested elements and the pH were within national standards and World Health Organization guidelines. The percentage of long-lived people in the area was closely related to the macro- and micro-element contents of their staple food, rice. The elements in rice could be classified into three categories according to their effect on longevity: Sr, Ca, Al, Mo, and Se, which were positively correlated with longevity; Fe, Mn, Zn, Cr, P, Mg, and K, which had a weak effect on local longevity, and Cu and Ba, which had a negative effect on longevity.

Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations

PubMed Central

Li, Yang; Wang, Wen-Jing; Cao, Huiqing; Lu, Jiehua; Wu, Chong; Hu, Fang-Yuan; Guo, Jian; Zhao, Ling; Yang, Fan; Zhang, Yi-Xin; Li, Wei; Zheng, Gu-Yan; Cui, Hanbin; Chen, Xiaomin; Zhu, Zhiming; He, Hongbo; Dong, Birong; Mo, Xianming; Zeng, Yi; Tian, Xiao-Li

2009-01-01

FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations. Here we tested the genetic contribution of FOXO1A and FOXO3A to the longevity phenotype in Han Chinese population. Six tagging SNPs from FOXO1A and FOXO3A were selected and genotyped in 1817 centenarians and younger individuals. Two SNPs of FOXO1A were found to be associated with longevity in women (P = 0.01–0.005), whereas all three SNPs of FOXO3A were associated with longevity in both genders (P = 0.005–0.001). One SNP from FOXO1A was found not to be associated with longevity. In haplotype association tests, the OR (95% CI) for haplotypes TTG and CCG of FOXO1A in association with female longevity were 0.72 (0.58–0.90) and 1.38 (1.08–1.76), P = 0.0033 and 0.0063, respectively. The haplotypes of FOXO3A were associated with longevity in men [GTC: OR (95% CI) = 0.67 (0.51–0.86), P = 0.0014; CGT: OR (95% CI) = 1.48 (1.12–1.94), P = 0.0035] and in women [GTC: OR (95% CI) = 0.75 (0.60–0.94), P = 0.0094; CGT: OR (95% CI) = 1.47 (1.16–1.86), P = 0.0009]. The haplotype association tests were validated by permutation analysis. The association of FOXO1A with female longevity was replicated in 700 centenarians and younger individuals that were sampled geographically different from the original population. Thus, we demonstrate that, unlike FOXO3A, FOXO1A is more closely associated with human female longevity, suggesting that the genetic contribution to longevity trait may be affected by genders. PMID:19793722

Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes.

PubMed

Alam, Shafiul; Abdullah, Chowdhury S; Aishwarya, Richa; Orr, A Wayne; Traylor, James; Miriyala, Sumitra; Panchatcharam, Manikandan; Pattillo, Christopher B; Bhuiyan, Md Shenuarin

2017-08-31

C/EBP-homologous protein (CHOP) is a ubiquitously expressed stress-inducible transcription factor robustly induced by maladaptive endoplasmic reticulum (ER) stresses in a wide variety of cells. Here, we examined a novel function of Sigma 1 receptor (Sigmar1) in regulating CHOP expression under ER stress in cardiomyocytes. We also defined Sigmar1-dependent activation of the adaptive ER-stress pathway in regulating CHOP expression. We used adenovirus-mediated Sigmar1 overexpression as well as Sigmar1 knockdown by siRNA in neonatal rat ventricular cardiomyocytes (NRCs); to induce ER stress, cardiomyocytes were treated with tunicamycin. Sigmar1-siRNA knockdown significantly increased the expression of CHOP and significantly induced cellular toxicity by sustained activation of ER stress in cardiomyocytes. Sigmar1 overexpression decreased the expression of CHOP and significantly decreased cellular toxicity in cells. Using biochemical and immunocytochemical experiments, we also defined the specific ER-stress pathway associated with Sigmar1-dependent regulation of CHOP expression and cellular toxicity. We found that Sigmar1 overexpression significantly increased inositol requiring kinase 1α (IRE1α) phosphorylation and increased spliced X-box-binding proteins (XBP1s) expression as well as nuclear localization. In contrast, Sigmar1 knockdown significantly decreased IRE1α phosphorylation and decreased XBP1s expression as well as nuclear transport. Taken together, these results indicate that Sigmar1-dependent activation of IRE1α-XBP1s ER-stress response pathways are associated with inhibition of CHOP expression and suppression of cellular toxicity. Hence, Sigmar1 is an essential component of the adaptive ER-stress response pathways eliciting cellular protection in cardiomyocytes. © 2017 The Author(s).

Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes

PubMed Central

Alam, Shafiul; Abdullah, Chowdhury S.; Aishwarya, Richa; Orr, A. Wayne; Traylor, James; Miriyala, Sumitra; Panchatcharam, Manikandan; Pattillo, Christopher B.

2017-01-01

C/EBP-homologous protein (CHOP) is a ubiquitously expressed stress-inducible transcription factor robustly induced by maladaptive endoplasmic reticulum (ER) stresses in a wide variety of cells. Here, we examined a novel function of Sigma 1 receptor (Sigmar1) in regulating CHOP expression under ER stress in cardiomyocytes. We also defined Sigmar1-dependent activation of the adaptive ER-stress pathway in regulating CHOP expression. We used adenovirus-mediated Sigmar1 overexpression as well as Sigmar1 knockdown by siRNA in neonatal rat ventricular cardiomyocytes (NRCs); to induce ER stress, cardiomyocytes were treated with tunicamycin. Sigmar1-siRNA knockdown significantly increased the expression of CHOP and significantly induced cellular toxicity by sustained activation of ER stress in cardiomyocytes. Sigmar1 overexpression decreased the expression of CHOP and significantly decreased cellular toxicity in cells. Using biochemical and immunocytochemical experiments, we also defined the specific ER-stress pathway associated with Sigmar1-dependent regulation of CHOP expression and cellular toxicity. We found that Sigmar1 overexpression significantly increased inositol requiring kinase 1α (IRE1α) phosphorylation and increased spliced X-box-binding proteins (XBP1s) expression as well as nuclear localization. In contrast, Sigmar1 knockdown significantly decreased IRE1α phosphorylation and decreased XBP1s expression as well as nuclear transport. Taken together, these results indicate that Sigmar1-dependent activation of IRE1α-XBP1s ER-stress response pathways are associated with inhibition of CHOP expression and suppression of cellular toxicity. Hence, Sigmar1 is an essential component of the adaptive ER-stress response pathways eliciting cellular protection in cardiomyocytes. PMID:28667101

Association of FOXO3A variation with human longevity confirmed in German centenarians

PubMed Central

Flachsbart, Friederike; Caliebe, Amke; Kleindorp, Rabea; Blanché, Hélène; von Eller-Eberstein, Huberta; Nikolaus, Susanna; Schreiber, Stefan; Nebel, Almut

2009-01-01

The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin–IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987–13992]. However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A. Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans. PMID:19196970

Early Life Stress: Effects on the Regulation of Anxiety Expression in Children and Adolescents.

PubMed

Burkholder, Amanda R; Koss, Kalsea J; Hostinar, Camelia E; Johnson, Anna E; Gunnar, Megan R

2016-11-01

This study examined children's ( N = 79; 9-10 years) and adolescents' ( N = 82; 15-16 years) ability to regulate their emotion expressions of anxiety as they completed a modified version of the Trier Social Stress Test for Children (TSST-C). Approximately half in each age group were internationally adopted from institutional care ( N = 79) and half were non-adopted, age-matched peers ( N = 82). Institutional care was viewed as a form of early life stress. Coders who were reliable and blind to group status watched videos of the session to assess anxiety expressions using the Child and Adolescent Stress and Emotion Scale developed for this study. Children exhibited more expressions of anxiety than adolescents, and youth adopted from institutions showed more expressions of anxiety than their non-adopted counterparts. The role of early life stress on observed anxiety expressions remained significant after controlling for differences in age, physiological stress responses measured through salivary cortisol reactivity, and self-reports of stress during the TSST-C. This suggests possible deficits in the regulation of expressive behavior for youth with early life stress histories, which cannot be explained by experiencing the task as more stressful.

Early Life Stress: Effects on the Regulation of Anxiety Expression in Children and Adolescents

PubMed Central

Burkholder, Amanda R; Koss, Kalsea J.; Hostinar, Camelia E; Johnson, Anna E.; Gunnar, Megan R

2017-01-01

This study examined children’s (N = 79; 9–10 years) and adolescents’ (N = 82; 15–16 years) ability to regulate their emotion expressions of anxiety as they completed a modified version of the Trier Social Stress Test for Children (TSST-C). Approximately half in each age group were internationally adopted from institutional care (N = 79) and half were non-adopted, age-matched peers (N = 82). Institutional care was viewed as a form of early life stress. Coders who were reliable and blind to group status watched videos of the session to assess anxiety expressions using the Child and Adolescent Stress and Emotion Scale developed for this study. Children exhibited more expressions of anxiety than adolescents, and youth adopted from institutions showed more expressions of anxiety than their non-adopted counterparts. The role of early life stress on observed anxiety expressions remained significant after controlling for differences in age, physiological stress responses measured through salivary cortisol reactivity, and self-reports of stress during the TSST-C. This suggests possible deficits in the regulation of expressive behavior for youth with early life stress histories, which cannot be explained by experiencing the task as more stressful. PMID:28584408

Stress regulation and incision in borderline personality disorder--a pilot study modeling cutting behavior.

PubMed

Reitz, Sarah; Krause-Utz, Annegret; Pogatzki-Zahn, Esther M; Ebner-Priemer, Ulrich; Bohus, Martin; Schmahl, Christian

2012-08-01

Emotion dysregulation in Borderline Personality Disorder (BPD) is characterized by high baseline negative intensity, high reactivity, and slow return to baseline. Patients with BPD often engage in self-injurious behavior because it leads to immediate relief of stress levels. We aimed to assess stress regulation as well as the influence of tissue damage on subjective (aversive tension) and objective (heart rate) stress correlates in BPD. In 14 unmedicated patients with BPD and 18 healthy controls, a stress induction was followed by an incision into the forearm conducted by an investigator. For aversive tension, we found elevated baseline levels as well as slower return to baseline in BPD. In controls, incision resulted in a short-term increase of aversive tension, whereas tension and heart rate decreased in the BPD group. Our preliminary results support the hypothesis that tissue damage may play a role in disturbed stress regulation in BPD.

Translational genomics for improving sow reproductive longevity

USDA-ARS?s Scientific Manuscript database

Sow reproductive longevity is a composite trait that is expressed throughout life that depends on the potential of females to resume ovarian cyclicity, re-breed, and farrow multiple parities. Approximately 50% of sows are culled annually with more than one third due to poor fertility. Age at puberty...

Shear stress regulates endothelial microparticle release.

PubMed

Vion, Anne-Clémence; Ramkhelawon, Bhama; Loyer, Xavier; Chironi, Gilles; Devue, Cecile; Loirand, Gervaise; Tedgui, Alain; Lehoux, Stéphanie; Boulanger, Chantal M

2013-05-10

Endothelial activation and apoptosis release membrane-shed microparticles (EMP) that emerge as important biological effectors. Because laminar shear stress (SS) is a major physiological regulator of endothelial survival, we tested the hypothesis that SS regulates EMP release. EMP levels were quantified by flow cytometry in medium of endothelial cells subjected to low or high SS (2 and 20 dyne/cm(2)). EMP levels augmented with time in low SS conditions compared with high SS conditions. This effect was sensitive to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Rho kinases inhibitors but unaffected by caspase inhibitors. Low SS-stimulated EMP release was associated with increased endothelial Rho kinases and ERK1/2 activities and cytoskeletal reorganization. Overexpression of constitutively active RhoA stimulated EMP release under high SS. We also examined the effect of nitric oxide (NO) in mediating SS effects. L-NG-nitroarginine methyl ester (L-NAME), but not D-NG-nitroarginine methyl ester, increased high SS-induced EMP levels by 3-fold, whereas the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) decreased it. L-NAME and SNAP did not affect Rho kinases and ERK1/2 activities. Then, we investigated NO effect on membrane remodeling because microparticle release is abolished in ABCA1-deficient cells. ABCA1 expression, which was greater under low SS than under high SS, was augmented by L-NAME under high SS and decreased by SNAP under low SS conditions. Altogether, these results demonstrate that sustained atheroprone low SS stimulates EMP release through activation of Rho kinases and ERK1/2 pathways, whereas atheroprotective high SS limits EMP release in a NO-dependent regulation of ABCA1 expression and of cytoskeletal reorganization. These findings, therefore, identify endothelial SS as a physiological regulator of microparticle release.

Mediterranean Way of Drinking and Longevity.

PubMed

Giacosa, Attilio; Barale, Roberto; Bavaresco, Luigi; Faliva, Milena Anna; Gerbi, Vincenzo; La Vecchia, Carlo; Negri, Eva; Opizzi, Annalisa; Perna, Simone; Pezzotti, Mario; Rondanelli, Mariangela

2016-01-01

The relation between alcohol consumption and mortality is a J-shaped curve in most of the many studies published on this topic. The Copenhagen Prospective Population Studies demonstrated in the year 2000 that wine intake may have a beneficial effect on all cause mortality that is additive to that of alcohol. Wine contains various poliphenolic substances which may be beneficial for health and in particular flavonols (such as myricetin and quercetin), catechin and epicatechin, proanthocyanidins, anthocyanins, various phenolic acids and the stilbene resveratrol. In particular, resveratrol seems to play a positive effect on longevity because it increases the expression level of Sirt1, besides its antioxidant, anti-inflammatory and anticarcinogenic properties. Moderate wine drinking is part of the Mediterranean diet, together with abundant and variable plant foods, high consumption of cereals, olive oil as the main (added) fat and a low intake of (red) meat. This healthy diet pattern involves a "Mediterranean way of drinking," that is a regular, moderate wine consumption mainly with food (up to two glasses a day for men and one glass for women). Moderate wine drinking increases longevity, reduces the risk of cardiovascular diseases and does not appreciably influence the overall risk of cancer.

[Effect of physical activity on longevity].

PubMed

Wilczek, Mateusz M; Krupienicz, Andrzej

2016-11-25

Multiple population studies have reported a positive correlation between higher levels of physical activity (PA) and longer lifespan. It has been generally accepted that it occurs due to PA having a direct effect on longevity. However, this idea is negated by experiments on animal models and an observational study on a twin cohort published recently by Karvinen et al. This unique study includes a pairwise comparison of monozygotic twins discordant for PA, therefore eliminating any influence of genetic factors on both mortality and tendency to take up exercise. The intriguing lack of differences in lifespan in such pairs implies that PA is not an important life prolonging factor. This discovery casts doubt on the validity of PA recommendations found in numerous medical guidelines. Nevertheless, the mentioned results apply only to the plain PA - longevity relation. They do not consider health benefits of PA, for which solid evidence exists. In particular, PA clearly reduces the risk of obesity-related diseases. This may indirectly yet significantly affect the length and quality of life, even if the direct relationship between PA and lifespan will be proven false in further research. © 2016 MEDPRESS.

Autonomic regulation in response to stress: The influence of anticipatory emotion regulation strategies and trait rumination.

PubMed

Nasso, Selene; Vanderhasselt, Marie-Anne; Demeyer, Ineke; De Raedt, Rudi

2018-05-21

According to the neurocognitive framework for regulation expectation, adaptively regulating emotions in anticipation of a stressful event should help individuals deal with the stressor itself. The goal of this study was twofold: first, the authors compared the influence of adaptive versus maladaptive anticipatory emotion regulation (ER) on the autonomic system during anticipation of, confrontation with, and recovery from a stressor; second, they explored whether trait rumination moderated this relationship. The authors collected data from 56 healthy female undergraduates during a public speaking task. The task involved 4 phases: baseline, anticipatory ER, stressor, and recovery. Participants were assigned to 1 of 2 anticipatory ER instructions (reappraisal or catastrophizing). Heart rate variability (HRV) indexed autonomic regulation. Results confirmed that HRV was higher in the reappraisal than in the catastrophizing group (over all time points, except for baseline). Trait rumination levels moderated the effect of anticipatory ER strategy on HRV during the stressor phase. Specifically, whereas for low ruminators reappraisal (versus catastrophizing) in the anticipation phase led to higher HRV when confronted to the stressor, high ruminators demonstrated lower HRV in that same condition. To conclude, over all participants, using reappraisal during the anticipation phase allowed participants to better cope with stress. However, only low, but not high ruminators could profit from the beneficial effect of anticipatory reappraisal on autonomic regulation. Even though further research is needed, this study suggests that, in female undergraduates, the tendency to ruminate is associated with abnormal anticipatory ER that might hinder an adaptive response to a stressor. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The cell non-autonomous function of ATG-18 is essential for neuroendocrine regulation of Caenorhabditis elegans lifespan

PubMed Central

Minnerly, Justin; Zhang, Jiuli; Parker, Thomas

2017-01-01

Dietary restriction (DR) and reduced insulin growth factor (IGF) signaling extend lifespan in Caenorhabditis elegans and other eukaryotic organisms. Autophagy, an evolutionarily conserved lysosomal degradation pathway, has emerged as a central pathway regulated by various longevity signals including DR and IGF signaling in promoting longevity in a variety of eukaryotic organisms. However, the mechanism remains unclear. Here we show that the autophagy protein ATG-18 acts cell non-autonomously in neuronal and intestinal tissues to maintain C. elegans wildtype lifespan and to respond to DR and IGF-mediated longevity signaling. Moreover, ATG-18 activity in chemosensory neurons that are involved in food detection sufficiently mediates the effect of these longevity pathways. Additionally, ATG-18-mediated cell non-autonomous signaling depends on the release of neurotransmitters and neuropeptides. Interestingly, our data suggest that neuronal and intestinal ATG-18 acts in parallel and converges on unidentified neurons that secrete neuropeptides to regulate C. elegans lifespan through the transcription factor DAF-16/FOXO in response to reduced IGF signaling. PMID:28557996

Organization and Regulation of Soybean SUMOylation System under Abiotic Stress Conditions

PubMed Central

Li, Yanjun; Wang, Guixin; Xu, Zeqian; Li, Jing; Sun, Mengwei; Guo, Jingsong; Ji, Wei

2017-01-01

Covalent attachment of the small ubiquitin-related modifier, SUMO, to substrate proteins plays a significant role in plants under stress conditions, which can alter target proteins' function, location, and protein-protein interactions. Despite this importance, information about SUMOylation in the major legume crop, soybean, remains obscure. In this study, we performed a bioinformatics analysis of the entire soybean genome and identified 40 genes belonged to six families involved in a cascade of enzymatic reactions in soybean SUMOylation system. The cis-acting elements analysis revealed that promoters of SUMO pathway genes contained different combinations of stress and development-related cis-regulatory elements. RNA-seq data analysis showed that SUMO pathway components exhibited versatile tissue-specific expression patterns, indicating coordinated functioning during plant growth and development. qRT-PCR analysis of 13 SUMO pathway members indicated that majority of the SUMO pathway members were transcriptionally up-regulated by NaCl, heat and ABA stimuli during the 24 h period of treatment. Furthermore, SUMOylation dynamics in soybean roots under abiotic stress treatment were analyzed by western blot, which were characterized by regulation of SUMOylated proteins. Collectively, this study defined the organization of the soybean SUMOylation system and implied an essential function for SUMOylation in soybean abiotic stress responses. PMID:28878795

A Functional Antagonistic Relationship between Auxin and Mitochondrial Retrograde Signaling Regulates Alternative Oxidase1a Expression in Arabidopsis1[W][OPEN

PubMed Central

Ivanova, Aneta; Law, Simon R.; Narsai, Reena; Duncan, Owen; Lee, Jae-Hoon; Zhang, Botao; Van Aken, Olivier; Radomiljac, Jordan D.; van der Merwe, Margaretha; Yi, KeKe; Whelan, James

2014-01-01

The perception and integration of stress stimuli with that of mitochondrion function are important during periods of perturbed cellular homeostasis. In a continuous effort to delineate these mitochondrial/stress-interacting networks, forward genetic screens using the mitochondrial stress response marker alternative oxidase 1a (AOX1a) provide a useful molecular tool to identify and characterize regulators of mitochondrial stress signaling (referred to as regulators of alternative oxidase 1a [RAOs] components). In this study, we reveal that mutations in genes coding for proteins associated with auxin transport and distribution resulted in a greater induction of AOX1a in terms of magnitude and longevity. Three independent mutants for polarized auxin transport, rao3/big, rao4/pin-formed1, and rao5/multidrug-resistance1/abcb19, as well as the Myb transcription factor rao6/asymmetric leaves1 (that displays altered auxin patterns) were identified and resulted in an acute sensitivity toward mitochondrial dysfunction. Induction of the AOX1a reporter system could be inhibited by the application of auxin analogs or reciprocally potentiated by blocking auxin transport. Promoter activation studies with AOX1a::GUS and DR5::GUS lines further confirmed a clear antagonistic relationship between the spatial distribution of mitochondrial stress and auxin response kinetics, respectively. Genome-wide transcriptome analyses revealed that mitochondrial stress stimuli, such as antimycin A, caused a transient suppression of auxin signaling and conversely, that auxin treatment repressed a part of the response to antimycin A treatment, including AOX1a induction. We conclude that mitochondrial stress signaling and auxin signaling are reciprocally regulated, balancing growth and stress response(s). PMID:24820025

Why Combatting Teachers' Stress Is Everyone's Job

ERIC Educational Resources Information Center

Clement, Mary

2017-01-01

Teacher stressors and the effects of stressors on teachers' decisions to remain in the profession are reviewed in this article. A discussion of what teachers can do to combat their stress and perform their duties for longevity in the classroom includes practical and researched strategies. Teachers cannot be expected to resolve all the issues of…

Physiological Regulation of Stress in Referred Adolescents: The Role of the Parent-Adolescent Relationship

ERIC Educational Resources Information Center

Willemen, Agnes M.; Schuengel, Carlo; Koot, Hans M.

2009-01-01

Background: Psychopathology in youth appears to be linked to deficits in regulating affective responses to stressful situations. In children, high-quality parental support facilitates affect regulation. However, in adolescence, the role of parent-child interaction in the regulation of affect is unclear. This study examined physiological reactivity…

Educators' emotion regulation strategies and their physiological indicators of chronic stress over 1 year.

PubMed

Katz, Deirdre A; Harris, Alexis; Abenavoli, Rachel; Greenberg, Mark T; Jennings, Patricia A

2018-04-01

Studies show teaching is a highly stressful profession and that chronic work stress is associated with adverse health outcomes. This study analysed physiological markers of stress and self-reported emotion regulation strategies in a group of middle school teachers over 1 year. Chronic physiological stress was assessed with diurnal cortisol measures at three time points over 1 year (fall, spring, fall). The aim of this longitudinal study was to investigate the changes in educators' physiological level of stress. Results indicate that compared to those in the fall, cortisol awakening responses were blunted in the spring. Further, this effect was ameliorated by the summer break. Additionally, self-reported use of the emotion regulation strategy reappraisal buffered the observed blunting that occurred in the spring. Copyright © 2017 John Wiley & Sons, Ltd.

High throughput sequencing reveals novel and abiotic stress-regulated microRNAs in the inflorescences of rice.

PubMed

Barrera-Figueroa, Blanca E; Gao, Lei; Wu, Zhigang; Zhou, Xuefeng; Zhu, Jianhua; Jin, Hailing; Liu, Renyi; Zhu, Jian-Kang

2012-08-03

MicroRNAs (miRNAs) are small RNA molecules that play important regulatory roles in plant development and stress responses. Identification of stress-regulated miRNAs is crucial for understanding how plants respond to environmental stimuli. Abiotic stresses are one of the major factors that limit crop growth and yield. Whereas abiotic stress-regulated miRNAs have been identified in vegetative tissues in several plants, they are not well studied in reproductive tissues such as inflorescences. We used Illumina deep sequencing technology to sequence four small RNA libraries that were constructed from the inflorescences of rice plants that were grown under control condition and drought, cold, or salt stress. We identified 227 miRNAs that belong to 127 families, including 70 miRNAs that are not present in the miRBase. We validated 62 miRNAs (including 10 novel miRNAs) using published small RNA expression data in DCL1, DCL3, and RDR2 RNAi lines and confirmed 210 targets from 86 miRNAs using published degradome data. By comparing the expression levels of miRNAs, we identified 18, 15, and 10 miRNAs that were regulated by drought, cold and salt stress conditions, respectively. In addition, we identified 80 candidate miRNAs that originated from transposable elements or repeats, especially miniature inverted-repeat elements (MITEs). We discovered novel miRNAs and stress-regulated miRNAs that may play critical roles in stress response in rice inflorescences. Transposable elements or repeats, especially MITEs, are rich sources for miRNA origination.

Effects of hierarchical features on longevity of submerged superhydrophobic surfaces with parallel grooves

NASA Astrophysics Data System (ADS)

Hemeda, A. A.; Gad-el-Hak, M.; Tafreshi, H. Vahedi

2014-08-01

While the air-water interface over superhydrophobic surfaces decorated with hierarchical micro- or nanosized geometrical features have shown improved stability under elevated pressures, their underwater longevity—-the time that it takes for the surface to transition to the Wenzel state—-has not been studied. The current work is devised to study the effects of such hierarchical features on the longevity of superhydrophobic surfaces. For the sake of simplicity, our study is limited to superhydrophobic surfaces composed of parallel grooves with side fins. The effects of fins on the critical pressure—-the pressure at which the surface starts transitioning to the Wenzel state—-and longevity are predicted using a mathematical approach based on the balance of forces across the air-water interface. Our results quantitatively demonstrate that the addition of hierarchical fins significantly improves the mechanical stability of the air-water interface, due to the high advancing contact angles that can be achieved when an interface comes in contact with the fins sharp corners. For longevity on the contrary, the hierarchical fins were only effective at hydrostatic pressures below the critical pressure of the original smooth-walled groove. Our results indicate that increasing the length of the fins decreases the critical pressure of a submerged superhydrophobic groove but increases its longevity. Increasing the thickness of the fins can improve both the critical pressure and longevity of a submerged groove. The mathematical framework presented in this paper can be used to custom-design superhydrophobic surfaces for different applications.

Yeast aquaporin regulation by 4-hydroxynonenal is implicated in oxidative stress response.

PubMed

Rodrigues, Claudia; Tartaro Bujak, Ivana; Mihaljević, Branka; Soveral, Graça; Cipak Gasparovic, Ana

2017-05-01

Reactive oxygen species, especially hydrogen peroxide (H 2 O 2 ), contribute to functional molecular impairment and cellular damage, but also are necessary in normal cellular metabolism, and in low doses play stimulatory role in cell proliferation and stress resistance. In parallel, reactive aldehydes such as 4-hydroxynonenal (HNE), are lipid peroxidation breakdown products which also contribute to regulation of numerous cellular processes. Recently, channeling of H 2 O 2 by some mammalian aquaporin isoforms has been reported and suggested to contribute to aquaporin involvement in cancer malignancies, although the mechanism by which these membrane water channels are implicated in oxidative stress is not clear. In this study, two yeast models with increased levels of membrane polyunsaturated fatty acids (PUFAs) and aquaporin AQY1 overexpression, respectively, were used to evaluate their interplay in cell's oxidative status. In particular, the aim of the study was to investigate if HNE accumulation could affect aquaporin function with an outcome in oxidative stress response. The data showed that induction of aquaporin expression by PUFAs results in increased water permeability in yeast membranes and that AQY1 activity is impaired by HNE. Moreover, AQY1 expression increases cellular sensitivity to oxidative stress by facilitating H 2 O 2 influx. On the other hand, AQY1 expression has no influence on the cellular antioxidant GSH levels and catalase activity. These results strongly suggest that aquaporins are important players in oxidative stress response and could contribute to regulation of cellular processes by regulation of H 2 O 2 influx. © 2017 IUBMB Life, 69(5):355-362, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Health status and health dynamics in an empirical model of expected longevity.

PubMed

Benítez-Silva, Hugo; Ni, Huan

2008-05-01

Expected longevity is an important factor influencing older individuals' decisions such as consumption, savings, purchase of life insurance and annuities, claiming of Social Security benefits, and labor supply. It has also been shown to be a good predictor of actual longevity, which in turn is highly correlated with health status. A relatively new literature on health investments under uncertainty, which builds upon the seminal work by Grossman [Grossman, M., 1972. On the concept of health capital and demand for health. Journal of Political Economy 80, 223-255] has directly linked longevity with characteristics, behaviors, and decisions by utility maximizing agents. Our empirical model can be understood within that theoretical framework as estimating a production function of longevity. Using longitudinal data from the Health and Retirement Study, we directly incorporate health dynamics in explaining the variation in expected longevities, and compare two alternative measures of health dynamics: the self-reported health change, and the computed health change based on self-reports of health status. In 38% of the reports in our sample, computed health changes are inconsistent with the direct report on health changes over time. And another 15% of the sample can suffer from information losses if computed changes are used to assess changes in actual health. These potentially serious problems raise doubts regarding the use and interpretation of the computed health changes and even the lagged measures of self-reported health as controls for health dynamics in a variety of empirical settings. Our empirical results, controlling for both subjective and objective measures of health status and unobserved heterogeneity in reporting, suggest that self-reported health changes are a preferred measure of health dynamics.

The comparison of species longevity and size evolution in fossilized dinosaurs vs. fossilized mammals

NASA Astrophysics Data System (ADS)

Baeza, E.; Srinath, A.; Hernandez, A.; Heim, N.; Payne, J.

2016-12-01

For over 200 million years, two animal groups have been competing for dominance over Earth: the reptiles, (in this case, dinosaurs), and the mammals. At the beginning of the Triassic, mammals were small, rat-like creatures that were dwarfed by the dinosaurs. Dinosaurs progressively continued to grow larger throughout the Jurassic and Cretaceous periods, thus outweighing and outliving the current mammals. But at the end of the Cretaceous, the K-T mass extinction occurred, and that wiped out the dinosaurs from the face of the Earth. After the disappearance of dinosaurs, mammals started to grow larger to fill the niches that the dinosaurs left open. With this evolution in mammals, would they be able to match or even beat the dinosaur's previous records? To judge that, we need to utilize two significant factors to help judge our answer. The two factors that set them apart were body mass and longevity. Documenting the body mass shows us how much the animal weighed compared to other species. The heaviest animal in our data set weighed 77 tons. The other factor is longevity, which indicates how long a certain species has existed on a geologic time scale. The longest living animal species in our data set lived for over 20 million years. With all the data we have analyzed, we have conducted research on this subject to find out how terrestrial mammals contrasted dinosaurs in the terms of body mass and species longevity. Our research brought us to the conclusion that mammals could not overtake the body mass and longevity of dinosaurs. Although mammals came pretty close to overlapping the dinosaurs' body masses, they were just below them marginally. We had a similar pattern in longevity, where we found out that heavier animals tended to have longer longevity, therefore the dinosaurs came out on top. Additionally, we did another contrast between Mesozoic and Cenozoic mammals, where Cenozoic mammals were larger, but both had similar longevities.

Estimation of the effects of multipoint pacing on battery longevity in routine clinical practice.

PubMed

Akerström, Finn; Narváez, Irene; Puchol, Alberto; Pachón, Marta; Martín-Sierra, Cristina; Rodríguez-Mañero, Moisés; Rodríguez-Padial, Luis; Arias, Miguel A

2017-09-23

Multipoint pacing (MPP) permits simultaneous multisite pacing of the left ventricle (LV); initial studies suggest haemodynamic and clinical benefits over conventional (single LV site) cardiac resynchronization therapy (CRT). The aim of this study was to estimate the impact of MPP activation on battery longevity in routine clinical practice. Patient (n = 46) and device data were collected from two centres at least 3 months after MPP-CRT device implantation. Multipoint pacing programming was based on the maximal possible anatomical LV1/LV2 separation according to three predefined LV pacing capture threshold (PCT) cut-offs (≤1.5 V; ≤4.0 V; and ≤6.5 V). Estimated battery longevity was calculated using the programmed lower rate limit, lead impedances, outputs, and pacing percentages. Relative to the longevity for conventional CRT using the lowest PCT (8.9 ± 1.2 years), MPP activation significantly shortened battery longevity for all three PCT cut-offs (≤1.5 V, -5.6%; ≤4.0 V, -16.9%; ≤6.5 V, -21.3%; P's <0.001). When compared with conventional CRT based on longest right ventricle-LV delay (8.3 ± 1.3 years), battery longevity was significantly shortened for the MPP ≤ 4.0 V and ≤6.5 V cut-offs (-10.8 and -15.7%, respectively; P's <0.001). Maximal LV1/LV2 spacing was possible in 23.9% (≤1.5 V), 56.5% (≤4.0 V), and 69.6% (≤6.5 V) of patients. Multipoint pacing activation significantly reduces battery longevity compared with that for conventional CRT configuration. When reasonable MPP LV vector PCTs (≤4.0 V) are achieved, the decrease in battery longevity is relatively small which may prompt the clinician to activate MPP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Longevity of highway pavements in Illinois : 2000 update

DOT National Transportation Integrated Search

2002-12-01

Results of the latest round of pavement longevity studies in Illinois provide updated performance data through 2000 for HMAC, JRCP, : and CRCP new construction as well as AC overlays (first, second, and third overlays) of these original pavements. Th...

The Influence of Work-Related Chronic Stress on the Regulation of Emotion and on Functional Connectivity in the Brain

PubMed Central

Golkar, Armita; Johansson, Emilia; Kasahara, Maki; Osika, Walter; Perski, Aleksander; Savic, Ivanka

2014-01-01

Despite mounting reports about the negative effects of chronic occupational stress on cognitive and emotional functions, the underlying mechanisms are unknown. Recent findings from structural MRI raise the question whether this condition could be associated with a functional uncoupling of the limbic networks and an impaired modulation of emotional stress. To address this, 40 subjects suffering from burnout symptoms attributed to chronic occupational stress and 70 controls were investigated using resting state functional MRI. The participants' ability to up- regulate, down-regulate, and maintain emotion was evaluated by recording their acoustic startle response while viewing neutral and negatively loaded images. Functional connectivity was calculated from amygdala seed regions, using explorative linear correlation analysis. Stressed subjects were less capable of down-regulating negative emotion, but had normal acoustic startle responses when asked to up-regulate or maintain emotion and when no regulation was required. The functional connectivity between the amygdala and the anterior cingulate cortex correlated with the ability to down-regulate negative emotion. This connectivity was significantly weaker in the burnout group, as was the amygdala connectivity with the dorsolateral prefrontal cortex and the motor cortex, whereas connectivity from the amygdala to the cerebellum and the insular cortex were stronger. In subjects suffering from chronic occupational stress, the functional couplings within the emotion- and stress-processing limbic networks seem to be altered, and associated with a reduced ability to down-regulate the response to emotional stress, providing a biological substrate for a further facilitation of the stress condition. PMID:25184294

Local Transcriptional Control of YUCCA Regulates Auxin Promoted Root-Growth Inhibition in Response to Aluminium Stress in Arabidopsis.

PubMed

Liu, Guangchao; Gao, Shan; Tian, Huiyu; Wu, Wenwen; Robert, Hélène S; Ding, Zhaojun

2016-10-01