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ETS domain-containing transcription factor ERF (Ets2 repressor factor) (PE-2)


Angiotensin-Converting Enzyme Gene D/I Polymorphism in Relation to Endothelial Function and Endothelial-Released Factors in Chinese Women.

Many studies have investigated the relationship between angiotensin-converting enzyme ([i]ACE[/i]) D/I polymorphism and cardiovascular disease or endothelial dysfunction; however, hardly any of these studies has taken aging or menopause into consideration. Furthermore, despite that many studies have examined the regulatory effects of endothelial-released factors (ERFs) on endothelial function, no study has evaluated the relationship between ERFs and endothelial function with respect to [i]ACE[/i] D/I polymorphism and menopause status. To answer these questions, 391 healthy Chinese women over a wide range of ages (22-75 years) were enrolled and divided into pre-menopause group and post-menopause group. After [i]ACE[/i] D/I genotype being identified, the women were then classified into either DI/II or DD genotype. Flow-mediated dilatation (FMD) of brachial endothelium and plasma levels of ERFs: nitric oxide (NO), endothelin-1 (ET-1), and angiotensin II (Ang II) were measured. The results showed that frequencies of [i]ACE[/i] D/I genotypes were in accordance with the Hardy-Weinberg equilibrium, and the frequency of I allele was higher than D allele. In pre-menopause group, FMD was significantly higher in women of DI/II than DD ([i]P[/i] = 0.032), and age-dependent in both genotypes (DD, [i]P[/i] = 0.0472; DI/II, [i]P[/i] < 0.0001). In post-menopause group, FMD was similar between women of DI/II and DD, and age-dependent only in women of DI/II ([i]P[/i] < 0.0001). In pre-menopause group, Ang II level was significantly higher in women of DD than DI/II ([i]P[/i] = 0.029), and FMD was significantly correlated with all ERFs in women of DD (NO, [i]P[/i] = 0.032; ET-1, [i]P[/i] = 0.017; Ang II, [i]P[/i] = 0.002), but only with Ang II in women of DI/II ([i]P[/i] = 0.026). In post-menopause group, no significant difference was observed in any ERF between women of DI/II and DD, and FMD was only significantly correlated with ET-1 in women of DD ([i]P[/i] = 0.010). In summary, FMD in women of DI/II was superior to DD in pre-menopause and more age-dependent than DD in post-menopause, and FMD was closely associated with ERFs. In conclusion, Chinese women of DI/II seem to have lower risk than DD in pre-menopause, but similar risk as DD in post-menopause in developing cardiovascular disease.


  • ACE D/I gene polymorphism
  • Chinese women
  • aging
  • endothelial function
  • endothelial-released factors
  • menopause

Projections of Ambient Temperature- and Air Pollution-Related Mortality Burden Under Combined Climate Change and Population Aging Scenarios: a Review.

Climate change will affect mortality associated with both ambient temperature and air pollution. Because older adults have elevated vulnerability to both non-optimal ambient temperature (heat and cold) and air pollution, population aging can amplify future population vulnerability to these stressors through increasing the number of vulnerable older adults. We aimed to review recent evidence on projections of temperature- or air pollution-related mortality burden (i.e., number of deaths) under combined climate change and population aging scenarios, with a focus on evaluating the role of population aging in assessing these health impacts of climate change. We included studies published between 2014 and 2019 with age-specific population projections. We reviewed 16 temperature projection studies and 15 air pollution projection studies. Nine of the temperature studies and four of the air pollution studies took population aging into account by performing age-stratified analyses that utilized age-specific relationships between temperature or air pollution exposures and mortality (i.e., age-specific exposure-response functions (ERFs)). Population aging amplifies the projected mortality burden of temperature and air pollution under a warming climate. Compared with a constant population scenario, population aging scenarios lead to less reduction or even increases in cold-related mortality burden, resulting in substantial net increases in future overall (heat and cold) temperature-related mortality burden. There is strong evidence suggesting that to accurately assess the future temperature- and air pollution-related mortality burden of climate change, investigators need to account for the amplifying effect of population aging. Thus, all future studies should incorporate age-specific population size projections and age-specific ERFs into their analyses. These studies would benefit from refinement of age-specific ERF estimates.


  • Air pollution
  • Climate change
  • Mortality
  • Population aging
  • Projection
  • Temperature

Exome Sequencing Analysis Identifies Rare Variants in [i]ATM[/i] and [i]RPL8[/i] That Are Associated With Shorter Telomere Length.

Telomeres are important for maintaining genomic stability. Telomere length has been associated with aging, disease, and mortality and is highly heritable (∼82%). In this study, we aimed to identify rare genetic variants associated with telomere length using whole-exome sequence data. We studied 1,303 participants of the Erasmus Rucphen Family (ERF) study, 1,259 of the Rotterdam Study (RS), and 674 of the British Heart Foundation Family Heart Study (BHF-FHS). We conducted two analyses, first we analyzed the family-based ERF study and used the RS and BHF-FHS for replication. Second, we combined the summary data of the three studies in a meta-analysis. Telomere length was measured by quantitative polymerase chain reaction in blood. We identified nine rare variants significantly associated with telomere length ([i]p[/i]-value < 1.42 × 10 , minor allele frequency of 0.2-0.5%) in the ERF study. Eight of these variants (in [i]C11orf65[/i], [i]ACAT1[/i], [i]NPAT[/i], [i]ATM[/i], [i]KDELC2[/i], and [i]EXPH5[/i]) were located on chromosome 11q22.3 that contains [i]ATM[/i], a gene involved in telomere maintenance. Although we were unable to replicate the variants in the RS and BHF-FHS ([i]p[/i]-value ≥ 0.21), segregation analysis showed that all variants segregate with shorter telomere length in a family. In the meta-analysis of all studies, a nominally significant association with LTL was observed with a rare variant in [i]RPL8[/i] ([i]p[/i]-[i]value[/i] = 1.48 × 10 ), which has previously been associated with age. Additionally, a novel rare variant in the known [i]RTEL1[/i] locus showed suggestive evidence for association ([i]p[/i]-value = 1.18 × 10 ) with LTL. To conclude, we identified novel rare variants associated with telomere length. Larger samples size are needed to confirm these findings and to identify additional variants.


  • ATM
  • RPL8
  • aging
  • meta-analysis
  • telomere
  • whole exome sequencing

Extensive transcriptome changes during seasonal leaf senescence in field-grown black cottonwood (Populus trichocarpa Nisqually-1).

To better understand the molecular control of leaf senescence, we examined transcriptome changes during seasonal leaf senescence in Populus trichocarpa Nisqually-1, the Populus reference genome, growing in its natural habitat. Using monthly (from May to October) transcriptomes for three years (2009, 2015, and 2016), we identified 17,974 differentially expressed genes (DEGs; false discovery rate <0.05; log-fold change cutoff = 0) from 36,007 expressed Populus gene models. A total of 14,415 DEGs were directly related to transitions between four major developmental phases - growth, senescence initiation, reorganization, and senescence termination. These DEGs were significantly (p < 0.05) enriched in 279 gene ontology (GO) terms, including those related to photosynthesis, metabolic process, catalytic activity, protein phosphorylation, kinase activity, pollination, and transport. Also, there were 881 differentially expressed transcription factor (TF) genes from 54 TF families, notably bHLH, MYB, ERF, MYB-related, NAC, and WRKY. We also examined 28 DEGs known as alternative splicing (AS) factors that regulate AS process, and found evidence for a reduced level of AS activity during leaf senescence. Furthermore, we were able to identify a number of promoter sequence motifs associated with leaf senescence. This work provides a comprehensive resource for identification of genes involved in seasonal leaf senescence in trees, and informs efforts to explore the conservation and divergence of molecular mechanisms underlying leaf senescence between annual and perennial species.

MeSH Terms

  • Aging
  • Gene Expression Profiling
  • Gene Expression Regulation, Plant
  • Genome, Plant
  • Photosynthesis
  • Plant Leaves
  • Populus
  • Seasons
  • Transcription Factors
  • Transcriptome

The ERF transcription factor EPI1 is a negative regulator of dark-induced and jasmonate-stimulated senescence in [i]Arabidopsis[/i].

Identification of the factors involved in the regulation of senescence and the analysis of their function are important for both a biological understanding of the senescence mechanism and the improvement of agricultural productivity. In this study, we identified an [i]ERF[/i] gene termed [i]"ERF gene conferring Postharvest longevity Improvement 1[/i]" (EPI1) as a possible regulator of senescence in [i]Arabidopsis[/i]. We found that EPI1 possesses transcriptional repression activity and that the transgenic plants overexpressing [i]EPI1[/i] and expressing its chimeric repressor, [i]EPI1-SRDX[/i], commonly suppressed the darkness-induced senescence in their excised aerial parts. These transgenic plants additionally maintained a high level of chlorophyll, even after the methyl jasmonate (MeJA) treatment, which stimulated senescence in the dark. In addition, we found that senescence-induced and -reduced genes are down- and upregulated, respectively, in the MeJA-treated transgenic plants under darkness. Our results suggest that EPI1 functions as a negative regulator of the dark-induced and JA-stimulated senescence.


  • ERF
  • jasmonate
  • senescence
  • transcription factor

Transcriptional regulation of Lonicera japonica Thunb. during flower development as revealed by comprehensive analysis of transcription factors.

Lonicera japonica Thunb. flower has been used for the treatment of various diseases for a long time and attracted many studies on its potential effects. Transcription factors (TFs) regulate extensive biological processes during plant development. As the restricted reports of L. japonica on TFs, our work was carried out to better understand the TFs' regulatory roles under different developmental stages in L. japonica. In this study, 1316 TFs belonging to 52 families were identified from the transcriptomic data, and corresponding expression profiles during the L. japonica flower development were comprehensively analyzed. 917 (69.68%) TFs were differentially expressed. TFs in bHLH, ERF, MYB, bZIP, and NAC families exhibited obviously altered expression during flower growth. Based on the analysis of differentially expressed TFs (DETFs), TFs in MYB, WRKY, NAC and LSD families that involved in phenylpropanoids biosynthesis, senescence processes and antioxidant activity were detected. The expression of MYB114 exhibited a positive correlation with the contents of luteoloside; Positive correlation was observed among the expression of MYC12, chalcone synthase (CHS) and flavonol synthase (FLS), while negative correlation was observed between the expression of MYB44 and the synthases; The expression of LSD1 was highly correlated with the expression of SOD and the total antioxidant capacity, while the expression of LOL1 and LOL2 exhibited a negative correlation with them; Many TFs in NAC and WRKY families may be potentially involved in the senescence process regulated by hormones and reactive oxygen species (ROS). The expression of NAC19, NAC29, and NAC53 exhibited a positive correlation with the contents of ABA and H O , while the expression of WRKY53, WRKY54, and WRKY70 exhibited a negative correlation with the contents of JA, SA and ABA. Our study provided a comprehensive characterization of the expression profiles of TFs during the developmental stages of L. japonica. In addition, we detected the key TFs that may play significant roles in controlling active components biosynthesis, antioxidant activity and flower senescence in L. japonica, thereby providing valuable insights into the molecular networks underlying L. japonica flower development.

MeSH Terms

  • Chlorogenic Acid
  • Chromatography, High Pressure Liquid
  • Flowers
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Plant
  • Glucosides
  • Hydrogen Peroxide
  • Lonicera
  • Luteolin
  • Plant Proteins
  • Sequence Analysis, DNA
  • Transcription Factors


  • Flower development
  • Hormone
  • L.japonica
  • Senescence
  • Transcription factor

Impact of Alternatively Polyadenylated Isoforms of ETHYLENE RESPONSE FACTOR4 with Activator and Repressor Function on Senescence in [i]Arabidopsis thaliana[/i] L.

Leaf senescence is highly regulated by transcriptional reprogramming, implying an important role for transcriptional regulators. ETHYLENE RESPONSE FACTOR4 (ERF4) was shown to be involved in senescence regulation and to exist in two different isoforms due to alternative polyadenylation of its pre-mRNA. One of these isoforms, ERF4-R, contains an ERF-associated amphiphilic repression (EAR) motif and acts as repressor, whereas the other form, ERF4-A, is lacking this motif and acts as activator. Here, we analyzed the impact of these isoforms on senescence. Both isoforms were able to complement the delayed senescence phenotype of the [i]erf4[/i] mutant with a tendency of ERF4-A for a slightly better complementation. However, overexpression led to accelerated senescence of 35S:[i]ERF4-R[/i] plants but not of 35S:[i]ERF4-A[/i] plants. We identified [i]CATALASE3[/i] ([i]CAT3[/i]) as direct target gene of ERF4 in a yeast-one-hybrid screen. Both isoforms directly bind to the [i]CAT3[/i] promoter but have antagonistic effects on gene expression. The ratio of [i]ERF4-A[/i] to [i]ERF4-R[/i] mRNA changed during development, leading to a complex age-dependent regulation of CAT3 activity. The RNA-binding protein FPA shifted the R/A-ratio and [i]fpa[/i] mutants are pointing towards a role of alternative polyadenylation regulators in senescence.

MeSH Terms

  • Arabidopsis
  • Arabidopsis Proteins
  • Catalase
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Plant
  • Polyadenylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms
  • Repressor Proteins


  • Alternative polyadenylation
  • Arabidopsis
  • FPA
  • senescence regulation

Transcriptome analysis of leaf senescence in red clover ([i]Trifolium pratense[/i] L.).

Red clover ([i]Trifolium pratense[/i] L.) is an important cool-season legume plant, which is used as forage. Leaf senescence is a critical developmental process that negatively affects plant quality and yield. The regulatory mechanism of leaf senescence has been studied, and genes involved in leaf senescence have been cloned and characterized in many plants. However, those works mainly focused on model plants. Information about regulatory pathways and the genes involved in leaf senescence in red clover is very sparse. In this study, to better understand leaf senescence in red clover, transcriptome analysis of mature and senescent leaves was investigated using RNA-Seq. A total of about 35,067 genes were identified, and 481 genes were differentially expressed in mature and senescent leaves. Some identified differentially expressed genes showed similar expression patterns as those involved in leaf senescence in other species, such as Arabidopsis, [i]Medicago truncatula[/i] and rice. Differentially expressed genes were confirmed by quantitative real-time PCR (qRT-PCR). Genes involved in signal transduction, transportation and metabolism of plant hormones, transcription factors and plant senescence were upregulated, while the downregulated genes were primarily involved in nutrient cycling, lipid/carbohydrate metabolism, hormone response and other processes. There were 64 differentially expressed transcription factor genes identified by RNA-Seq, including ERF, WRKY, bHLH, MYB and NAC. A total of 90 genes involved in biosynthesis, metabolism and transduction of plant hormones, including abscisic acid, jasmonic acid, cyokinin, brassinosteroid, salicylic acid and ethylene, were identified. Furthermore, 207 genes with direct roles in leaf senescence were demonstrated, such as senescence-associated genes. These genes were associated with senescence in other plants. Transcriptome analysis of mature and senescent leaves in red clover provides a large number of differentially expressed genes. Further analysis and identification of senescence-associated genes can provide new insight into the regulatory mechanisms of leaf development and senescence in legume plant and red clover.


  • Early stage of leaf senescence
  • RNA-Seq
  • Red clover
  • Senescence associated gene

Molecular and functional characterization of ShNAC1, an NAC transcription factor from Solanum habrochaites.

NAC transcription factors (TFs) are important regulators of plant adaptation to abiotic stress. In this study, we functionally characterized an NAC TF, ShNAC1, from Solanum habrochaites. ShNAC1 was up-regulated by drought, cold, and salt stresses, and it displayed lower expression at the late stage of stress treatments than its orthologous gene in S. lycopersicum. Overexpression of ShNAC1 in tomato resulted in reduced cold, drought, and salt tolerance. Additionally, ShNAC1 displayed the highest expression in senescent leaf, and overexpressing ShNAC1 accelerated salt- and dark-induced leaf senescence. ShNAC1 was located in the nucleus without transactivation activity. RNA-seq analysis revealed that 81% (190 out of 234) differentially-expressed genes (DEGs) showed down-regulation in the transgenic line L2 compared with wild-type, suggesting that ShNAC1 may function as a transcriptional repressor. Among these down-regulated DEGs, many were involved in stress responses, such as SlHKT1;1, SlMAPKKK59, SlJA2, SlTIL, SlALDH2B1, etc. Noticeably, one ACS gene and three ACO genes involved in ethylene biosynthesis were up-regulated, while seven ERF genes in the ethylene signal transduction pathway were down-regulated in the transgenic lines, respectively. Our results suggested that ShNAC1 negatively regulates tolerance to abiotic stress in tomato probably by modulating the ethylene biosynthesis and signal transduction pathways.

MeSH Terms

  • Chlorophyll
  • Cold-Shock Response
  • Dehydration
  • Gene Expression Regulation, Plant
  • Genes, Plant
  • Plant Proteins
  • Salt Tolerance
  • Solanum
  • Trans-Activators


  • Abiotic stress
  • Ethylene
  • NAC transcription factor
  • Senescence
  • Solanum habrochaites
  • Tomato

Anti-aging properties of Ribes fasciculatum in Caenorhabditis elegans.

The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum (ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activity of ERF was determined by lifespan assay under normal culture condition. The survival rate of nematodes under various stress conditions was assessed to validate the effects of ERF on the stress tolerance. To determine the antioxidant potential of ERF, the superoxide dismutase (SOD) activities and intracellular reactive oxygen species (ROS) levels were investigated. The ERF-mediated change in SOD-3 expression was examined using GFP-expressing transgenic strain. The effects of ERF on the aging-related factors were investigated by reproduction assay and pharyngeal pumping assay. The intestinal lipofuscin levels of aged nematodes were also measured. The mechanistic studies were performed using selected mutant strains. Our results indicated that ERF showed potent lifespan extension effects on the wild-type nematode under both normal and various stress conditions. The ERF treatment also enhanced the activity and expression of superoxide dismutase (SOD) and attenuated the intracellular ROS levels. Moreover, ERF-fed nematodes showed decreased lipofuscin accumulation, indicating ERF might affect age-associated changes in C. elegans. The results of mechanistic studies indicated that there was no significant lifespan extension in ERF-treated daf-2, age-1, sir-2.1, and daf-16 null mutants, suggesting that they were involved in ERF-mediated lifespan regulation. In conclusion, R. fasciculatum confers increased longevity and stress resistance in C. elegans via SIR-2.1-mediated DAF-16 activation, dependent on the insulin/IGF signaling pathway.

MeSH Terms

  • Aging
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Humans
  • Longevity
  • Oxidative Stress
  • Plant Extracts
  • Reactive Oxygen Species
  • Ribes
  • Signal Transduction


  • Aging
  • Caenorhabditis elegans
  • Lifespan
  • Ribes fasciculatum
  • Stress tolerance

Event-related fields evoked by vocal response inhibition: a comparison of younger and older adults.

The current study examined event-related fields (ERFs) evoked by vocal response inhibition in a stimulus-selective stop-signal task. We compared inhibition-related ERFs across a younger and an older group of adults. Behavioural results revealed that stop-signal reaction times (RTs), go-RTs, ignore-stop RTs and failed stop RTs were longer in the older, relative to the younger group by 38, 123, 149 and 116 ms, respectively. The amplitude of the ERF M2 peak (approximately 200 ms after the stop signal) evoked on successful stop trials was larger compared to that evoked on both failed stop and ignore-stop trials. The M4 peak (approximately 450 ms after stop signal) was of larger amplitude in both successful and failed stops compared to ignore-stop trials. In the older group, the M2, M3 and M4 peaks were smaller in amplitude and peaked later in time (by 24, 50 and 76 ms, respectively). We demonstrate that vocal response inhibition-related ERFs exhibit a similar temporal evolution to those previously described for manual response inhibition: an early peak at 200 ms (i.e. M2) that differentiates successful from failed stopping, and a later peak (i.e. M4) that is consistent with a neural marker of response checking and error processing. Across groups, our data support a more general decline of stimulus processing speed with age.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Evoked Potentials
  • Humans
  • Inhibition, Psychological
  • Magnetoencephalography
  • Middle Aged
  • Psychomotor Performance
  • Reaction Time
  • Young Adult


  • Ageing and stop-signal task
  • Event-related fields
  • Magnetoencephalography
  • Response inhibition
  • Speech

SlERF36, an EAR-motif-containing ERF gene from tomato, alters stomatal density and modulates photosynthesis and growth.

The AP2 domain class of transcription factors is a large family of genes with various roles in plant development and adaptation but with very little functional information in plants other than Arabidopsis. Here, the characterization of an EAR motif-containing transcription factor, SlERF36, from tomato that affects stomatal density, conductance, and photosynthesis is described. Heterologous expression of SlERF36 under the CaMV35S promoter in tobacco leads to a 25-35% reduction in stomatal density but without any effect on stomatal size or sensitivity. Reduction in stomatal density leads to a marked reduction in stomatal conductance (42-56%) as well as transpiration and is associated with reduced CO₂ assimilation rates, reduction in growth, early flowering, and senescence. A prominent adaptive response of SlERF36 overexpressors is development of constitutively high non-photochemical quenching (NPQ) that might function as a protective measure to prevent damage from high excitation pressure. The high NPQ leads to markedly reduced light utilization and low electron transport rates even at low light intensities. Taken together, these data suggest that SlERF36 exerts a negative control over stomatal density and modulates photosynthesis and plant development through its direct or indirect effects.

MeSH Terms

  • Lycopersicon esculentum
  • Photosynthesis
  • Plant Proteins
  • Plant Stomata
  • Plants, Genetically Modified


  • ERF
  • flowering
  • non-photochemical quenching
  • photosynthesis
  • repressor
  • senescence
  • stomata
  • stomatal conductance
  • tobacco
  • tomato.

Taurine enhances the sexual response and mating ability in aged male rats.

It has been demonstrated that taurine is abundant in male reproductive organs, and can be biosynthesized by testis, but the taurine concentration will reduce with aging. The levels of serum LH, T, NOS, and NO were found to be obviously increased by taurine supplementation in aged rats in our previous study. In addition, aging will result in a significant decline in sexual response and function, which may be attributed to the androgen deficiency. Furthermore, NO has been proposed as a crucial mediator of penile erection. That makes us hypothesize that there is potential relationship between taurine decline and erection dysfunction in aged males. So the primary aim of the present study was to investigate the effect of taurine on male sexuality in rats. Taurine was offered in water to male aged (20 months old) rats for 110 days. The effects of taurine on the sexual response, mating ability, levels of serum reproductive hormones, and penile NOS and NO levels were investigated. The results showed that taurine can significantly reduce the EL and ML; obviously increase the ERF, MF, IF, and EJF; stimulate the secretion of GnRH, LH, and T; and elevate penis NOS and NO level in aged rats. The results indicated that taurine can enhance the sexual response and mating ability in aged male rats by increasing the level of testosterone and NO, but the exact mechanism of which needs to be further investigated.

MeSH Terms

  • Aging
  • Animals
  • Ejaculation
  • Estradiol
  • Female
  • Follicle Stimulating Hormone
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Male
  • Mating Preference, Animal
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Penile Erection
  • Penis
  • Rats
  • Rats, Wistar
  • Sexual Behavior, Animal
  • Taurine
  • Testosterone