Lectin-like ox-LDL receptor-1 (LOX-1) plays an important role in inflammatory diseases, such as atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates LDL receptor degradation and influences serum levels. The present study was designed to investigate the possible interaction between PCSK9 LOX-1. In first set of experiments, human vascular endothelial cells smooth muscle were studied at baseline after lipopolysaccharide (LPS) treatment (to create state). Both LOX-1...

Summary The great majority of lifespan‐augmenting mutations were discovered in the nematode Caenorhabditis elegans . In particular, genetic disruption insulin‐like signaling extends longevity 1.5‐ to 3‐fold nematode, and lesser degrees other taxa, including fruit flies mice. C. strains bearing homozygous nonsense age‐1 gene, which encodes class‐I phosphatidylinositol 3‐kinase catalytic subunit (PI3K CS ), produce progeny that thought undergo obligatory developmental arrest. We now find that,...

Mitochondrial DNA was quantitated in total of various normal and mutant strains human diploid fibroblasts (finite replicative lifespan) permanent cell lines, using Southern-transfer hybridization to 32P-labeled pure mtDNA probe saturation 'H-labeled cRNA copied from mtDNA.In six fibroblast strains, copy number increased during serial passage roughly proportion volume or protein content, whereas normalized content per pg depended upon uiuo donor age but not level ("in uitro" age).Copy numbers...

Genes that play a role in the senescent arrest of cellular replication are likely to be overexpressed human diploid fibroblasts (HDF) derived from subjects with Werner syndrome (WS) because these cells have severely curtailed replicative life span. To identify some genes, cDNA library was constructed WS HDF after they had been serum depleted and repleted (5 days medium containing 1% followed by 24 h 20% serum). Differential screening 7,500 colonies revealed 102 clones hybridized...

Many lifespan-modulating genes are involved in either generation of oxidative substrates and end-products, or their detoxification removal. Among such metabolites, only lipoperoxides have the ability to produce free-radical chain reactions. For this study, fatty-acid profiles were compared across a panel C. elegans mutants that span tenfold range longevities uniform genetic background. Two lipid structural properties correlated extremely well with lifespan these worms: length susceptibility...

Abstract Introduction Alzheimer apolipoprotein E ( APOE ) ɛ4/ɛ4 carriers have earlier disease onset and more protein aggregates than patients with other genotypes. Autophagy opposes aggregation, important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to “coordinated lysosomal expression regulation” (CLEAR) DNA motifs. Methods Autophagic gene was assessed in brains of controls Alzheimer's (AD) parsed genotype a glioblastoma cell line expressing either...

Normal diploid cells have a limited replicative potential in culture, with progressively increasing interdivision time. Rarely, cell lines arise which can divide indefinitely; like tumor cells, such "immortal" display frequent chromosomal aberrations may reflect high rates of recombination. Recombination frequencies within plasmid substrate were 3.5-fold higher nine immortal human than six untransformed strains. Expression HsRAD51, homolog the yeast RAD51 and Escherichia coli recA...

Oxidative stress and inflammation are leading risk factors for age-associated functional declines. We assessed aspirin effects on endogenous oxidative-stress levels, lifespan, age-related declines, in the nematode Caenorhabditis elegans.Both its salicylate moiety, at nontoxic concentrations (0.5-1 mM), attenuated levels of reactive oxygen species (p<0.001), upregulated antioxidant genes encoding superoxide dismutases (especially sod-3, p<0.001), catalases ctl-2, p<0.0001), two...

Neurodegenerative diseases are largely defined by protein aggregates in affected tissues. Aggregates contain some shared components as well proteins thought to be specific for each disease. Aggregation has not previously been reported the normal, aging heart or hypertensive heart. Detergent-insoluble were isolated from mouse and characterized on 2-dimensional gels. Their levels increased markedly significantly with after sustained angiotensin II-induced hypertension. Of aggregate identified...

OPINION article Front. Genet., 20 July 2012 | https://doi.org/10.3389/fgene.2012.00134

Neurodegenerative diseases are distinguished by characteristic protein aggregates initiated disease-specific 'seed' proteins; however, roles of other co-aggregated proteins remain largely unexplored. Compact hippocampal were purified from Alzheimer's and control-subject pools using magnetic-bead immunoaffinity pulldowns. Their components fractionated electrophoretic mobility analyzed high-resolution proteomics. Although total detergent-insoluble controls had similar content, within the...

We collected 60 age-dependent transcriptomes for C. elegans strains including four exceptionally long-lived mutants (mean adult lifespan extended 2.2- to 9.4-fold) and three examples of lifespan-increasing RNAi treatments. Principal Component Analysis (PCA) reveals aging as a transcriptomic drift along single direction, consistent across the vastly diverse biological conditions coinciding with first principal component, hallmark criticality underlying gene regulatory network. therefore...

Glial fibrillary acidic protein (GFAP) is an intermediate filament structural involved in cytoskeleton assembly and integrity, expressed high abundance activated glial cells. GFAP neuroprotective, as knockout mice are hypersensitive to traumatic brain injury. cerebrospinal fluid a biomarker of Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal (FTD). Here, we present novel evidence that markedly overexpressed differentially phosphorylated AD hippocampus, especially the...

Abstract Purpose: The aim of this study was to test the efficacy telomestatin, an intramolecular G-quadruplex intercalating drug with specificity for telomeric sequences, as a potential therapeutic agent multiple myeloma. Experimental Design: We treated ARD, ARP, and MM1S myeloma cells various concentrations telomestatin 7 days evaluated telomerase activity. Myeloma were minimal effective concentration 3–5 weeks. Every 7th day fraction live determined by trypan blue exclusion, aliquots...

Summary Caenorhabditis elegans expresses a glutathione transferase (GST) belonging to the Pi class, for which we propose name CeGSTP2‐2. CeGSTP2‐2 (the product of gst‐10 gene) has ability conjugate lipid peroxidation 4‐hydroxynonenal (4‐HNE). Transgenic C. strains were generated in 5′‐flanking region and promoter placed upstream mGsta4 cDNAs, respectively. encodes murine mGSTA4‐4, an enzyme with particularly high catalytic efficiency 4‐HNE. The localization both transgenes was similar that...

Abstract Peak bone mineral density (BMD) is a highly heritable trait in humans and currently the best predictor of skeletal fragility underlying osteoporosis. The SAMP6 mouse strain displays unusually low BMD at maturity, age-dependent osteopenia associated with defective osteoblastogenesis. To identify quantitative loci (QTLs) influencing density, we constructed crosses between either AKR/J or SAMP6, two related strains higher peak BMD. Due to common ancestry these strains, intercross...

We have examined DNA methylation in diploid human fibroblasts, early and late their replicative life-span. The extent of -C-C-G-G- was measured by comparison fragment sizes after digestion with methylation-specific restriction enzyme Hpa II or Msp I, both. Methylation sites total DNA, occurring predominantly at internal (3′) cytosines, increased from 59% to 64% one cell strain passage, remained constant another, decreased four other strains (54% 48%, 58.5% 55% 51.5%, 52% 44.5%). Base...

PARP1/2 are required for single-strand break repair, and their inhibition causes DNA replication fork collapse double-strand (DSB) formation. These DSBs primarily repaired via homologous recombination (HR), a high-fidelity repair pathway. Should HR be deficient, may error-prone nonhomologous end-joining mechanisms, or persist, ultimately resulting in cell death. The combined disruption of PARP activities thus produces synthetic lethality. Multiple myeloma cells characterized by chromosomal...

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests involvement fundamental mechanisms, although these remain a subject debate. To help decipher mechanisms DR, we first compiled list genes that if genetically altered disrupt or prevent effects DR. We called DR–essential identified more than 100 model organisms such as yeast, worms,...