Abstract Archive

This searchable list includes the abstracts of all presentations given at a conference organised as part of the SENS series. We regret that the videos recorded at SENS3 and SENS4 are currently unavailable.

Association Of GSTM1 And GSTT1 Gene Deletions With Susceptibility To DNA Damage In The Pesticide Exposed Workers Of Punjab

Authors: S. Abhishek, N. Kaur, S. Kaur, M. Lata, J.K. Sharma, A. Sharma

The main aim of the present study was to evaluate genotoxic effects of pesticides in association with GST polymorphism. To achieve this aim DNA damage and genotypes of GSTM1 and GSTT1 genes were studied from blood lymphocytes of pesticide exposed and unexposed (control) agricultural workers of Punjab (north-west India). The blood samples were collected from 40 exposed and 27 unexposed subjects from Kakrala and Sanour villages of district Patiala. The DNA damage was evaluated by using alkaline comet assay.

Keywords: Pesticide, Comet Assay, % DNA in tail, GSTT1 and GSTM1

Modulation of wound healing in vitro by iP-associated factors

Authors: A. Abramovich, N. Aizenberg, A. Luria, A. Braiman, H. Yanai, M. Wolfson, V.E. Fraifeld

Induction of Pluripotency (iP) has been shown to produce autologous stem cells that are viable for cell replacement therapy, with potential rejuvenative effect. Yet, the biological consequences of this process or iP-associated factors have scarcely been explored. Wound healing (WH) in adults, unlike early embryos, is usually a non-regenerative process in which the end-result is scar formation and a reduction in tissue function. iP and associated factors may have implications on the pathway of wound healing (e.g., scar-free or scar-formation).

Keywords: wound healing, fibroblasts, induction of pluripotency

Retrodifferentiation and Aging: Harnessing Youth through Induction of Pluripotency in mature adult cells via Cell Surface Receptor Contact

Authors: I.S. Abuljadayel

Organiser's Note: The presenter of this talk withheld their permission for video to be published.

Keywords: Retrodifferentiation, Dedifferentiation, aging, Pluripotent Stem Cells, Regenerative Medicine

Differences in gene expression in the hippocampus of aged rats associated with better performance in inhibitory avoidance memory formation

Authors: G. Di Stefano, T. Casoli, D. Platano, P. Fattoretti, M. Balietti, B. Giorgetti, C. Bertoni-Freddari, F. Lattanzio, G. Aicardi

Alterations of long-term declarative memory formation occur to different degrees among individuals during normal aging, but the genetic basis for such differences are not yet fully understood. Aim of the present study was the identification of genes differently expressed in the hippocampus of aged (26-27 month old) rats showing diverse cognitive performance in a single trial inhibitory avoidance (IA) task. IA is a hippocampal-dependent aversive learning, based on contextual fear conditioning.

Keywords: inhibitory avoidance, memory formation, microarray, aging, hippocampus

Lets complete mitosens at first

Authors: M. Aoshima

Clearing damaged biomolecules is important, however our bodies do it normally. Even amyloid proteins are degraded by native cells. Previous study showed some extension of mouse life span by mitochondrial catalase. According to the result, however, there still is a significant damage in mtDNA. This might be because mtDNA is attached to matrix side of the inner membrane, thus decreasing the effectiveness of the catalase.

Keywords: membrane, oxidative, mtDNA, mitosens, mitochondria

Possible Novel RNA-Mediated Transcriptional Activation Mechanism, called "RNA memory" Involved in Cell Identity

Authors: W. Arancio, D. Corona

Position-effect variegation (PEV) was discovered in Drosophila melanogaster in 1930 in a study of X-ray-induced chromosomal rearrangements. If a rearrangement places euchromatic genes adjacent to a region of centromeric heterochromatin, it gives a variegated phenotype that results from the random inactivation of genes by heterochromatin spreading from the breakpoint. After the establishment, the inactivation is henceforth clonally inherited.

Keywords: PEV, RNA, Transinduction, Cell Identity, Transdifferentiation

Engineered Mesenchymal Stem Cells - The Road to Skeletal Tissue Regeneration

Authors: H. Aslan, D. Gazit

One of the leading causes for low back pain is the age-related degeneration of the intervertebral disc (IVD). Mesenchymal Stem Cells (MSCs) are excellent candidates for skeletal tissue engineering, and therefore we aimed to investigate stem cell-based platforms towards the treatment of IVD disorders. We have engineered MSCs to express the osteogenic gene, rhBMP-6, using a novel electroporation-based system, and injected them into the lumbar region of mice. The cells were able to fuse 2-3 vertebrae within 5 weeks, as indicated by quantitative, in vivo, micro CT analysis.

Keywords: Mesenchymal Stem Cells, Skeletal Tissue Engineering, Gene Therapy, Disc Degeneration

Currently Available Therapies with Autologous Stem Cells - From Basic Principles to Clinical Application

Authors: A. Bader, W. Brehm, C. Weber

Organiser's Note: The presenter of this talk withheld their permission for video to be published.

Keywords: Regenerative Medicine, Bioreactors, Liver, Biological Implants, Tissue Engineering

Synthesis of programmable integrases

Authors: R.M. Gordley, C.A. Gersbach, T. Gaj, C.F. Barbas III

The post-genomic era of medicine will be defined by our ability to achieve biological control through genetic reprogramming. New tools are needed to accurately rewrite the three billion base pair human genomic script and specifically alter genes, gene expression, and epigenetic state at any desired loci. To date, no enzyme - natural or synthetic - has been able to accurately modify only a single targeted site within the human genome. Recently, our studies have focuses on the development of a general strategy for the design of enzymes that target a single site within the genome.

Keywords: integrases, zinc finger, recombinase, ,

Femtosecond laser nanosurgery from shedding light on nerve regeneration to aiding in cancer diagnosis and therapy

Authors: A. Ben-Yakar

Organiser's Note: The presenter of this talk withheld their permission for video to be published.

Keywords: laser nanosurgery, microfluidics, nerve regeneration, cancer, C. elegans

Effects of mitochondrial gene deletion on tumorigenicity of metastatic melanoma: reassessing the Warburg effect

Authors: M.V. Berridge, A.S. Tan

The ability to switch energy production from oxidative phosphorylation to glycolysis in the presence of oxygen, the Warburg effect, has been observed in many tumours and is thought to represent a major biochemical switch associated with malignant transformation. Cells devoid of mitochondrial DNA that are deficient in aerobic respiration (ρo cells) have been used in our laboratory to model glycolytic switching.

Keywords: aerobic glycolysis, mitochondria, ROS, melanoma, metastasis

Influence of age-related protein modifications to prion protein aggregation

Authors: G. Panza, C. Dumpitak, D. Willbold, E. Birkmann

Protein glycation was viewed originally as a post-translational modification that accumulated mostly on extracellular proteins. Specifically, advanced glycation endproducts (AGEs) were thought to be formed slowly throughout life and the concentrations of AGEs found represent a life-long accumulation of the glycation adduct (1).

Keywords: prion, advanced glycation endproducts, protein aggregation, protein glycation,

Role of Shelterin in Cancer and Aging

Authors: M.A. Blasco

Shelterin is a highly conserved chromosome end-capping complex, which encompasses TRF1, TRF2, TPP1, POT1, TIN2 and RAP1. Although extensive cell culture studies suggest that shelterin is essential for telomere regulation, its role in telomere biology and disease in the context of the organism remained elusive due to lack of viable loss-of-function mouse models. I will first report here on mice and cells conditionally deleted for TRF1, TPP1 and RAP1.

Keywords: telomeres, shelterin, DNA damage, cancer, aging

Positive effect of HSP70 on lifespan of old NMRI mice

Authors: N.V. Bobkova, I.V. Artyuhov, N.I. Medvinskaya, N.N. Okladnikova, A.N. Samokhin, A.G. Peregudov

The properties of heat shock proteins (HSPs) and especially HSP70 draw attention for a number of reasons. HSP70 is an endogenous intracellular protein that has a variety of functions. HSP70 protects cells from cell death induced by various noxious stimuli and inhibits various cellular death pathways, decreases the infarction area after ischemia, (Klettner, 2004), and significantly increases the lifespan in drosophila and nematodes. A similar effect of HSP70 in mammals has not been described so far.

Keywords: Heat shock protein, HSP70, life span, mus musculus,

Comparison of oxidative stress status in patients with cardiogenic shock due to severe left ventricular dysfunction

Authors: J.C. Charniot, C. Cosson, X. Castellon, V. Bogdanova, D. Bonneflont-Rousselot, F. Chemouni, J.J. Monsuez, J.Y. Artigou, J.P. Albertini

Background: Oxidative stress (OS) implication is paramount in pathology: ischemia reperfusion sequence (acute coronary syndrome, cardiac surgery, transplantation). Involvement of OS in heart failure (HF) is less known but is increased in the failing heart, and this might contribute to the pathogenesis of myocardial remodeling and HF.

Aim: Prospective study to identify OS in plasma from patients with a cardiogenic shock and to evaluate etiologies of cardiomyopathy: ischemia or no.

Keywords: Oxidative stress (OS), cardiogenic shock, thiobarbituric acid-reactive substances (TBARS), arrhythmia,

Carnosine as natural antioxidant and geroprotector: from molecular mechanisms to clinical trials

Authors: A.A. Boldyrev, S.L. Stvolinsky, T.N. Fedorova, Z.A. Suslina

Carnosine is a neuroprotective dipeptide consisting of β-alanine and L-histidine accumulating in excitable tissues of vertebrates in concentrations varied between 2-40 mM. It demonstrates a number of useful activities including stimulation of brain and muscle microcirculation, activation of muscle working capacity, wound healing action on tissues and rejuvenating effect on cells cultured.

Keywords: Oxidative stress, Neurodegenerations, Carnosine, Natural antioxidant, Clinical trials

Role of growth hormone in methionine metabolism

Authors: H.M. Brown-Borg, S.G. Rakoczy

Various types of stress including environmental stressors and endogenous and exogenous compounds have been shown to affect longevity. Resistance to stress has been identified as a factor common to many long-living organisms. Ames dwarf mice exhibit growth hormone deficiency, enhanced antioxidative defense capacity, increased insulin sensitivity and a remarkable life span extension compared to normal, wild type mice. Elevated tissue glutathione levels contribute to the enhanced antioxidative defense and detoxification activities observed in dwarf mice.

Keywords: stress resistance, methionine, dwarf mice, ,

Immune Regulation in Frail Elderly

Authors: G. Colonna-Romano, M. Bulati, S. Buffa, M. Pellicanò, G. Candore, C. Caruso

Frailty is a state of critically impaired homeostasis that results in heightened vulnerability to stressors. It is common in older persons and associated with adverse health outcomes. We have focused our attention on two different frailty systems, the first group of subjects affected by cardiovascular disease and the second one by Alzheimer's Disease. It is believed that cells with regulatory functions play a central role in the control of autoimmunity and inflammation.

Keywords: Regulatory cells, frailty, aging, ,

Association between PECAM-1 polymorphisms and atherosclerosis: results of a study on patients from Northern Italy

Authors: F. Listì, C. Caruso, C. Falcone, C. Boiocchi, M. Cuccia, G. Candore

Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leucocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule-1 (PECAM-1), involved in this migration, has been associated with the development of atherosclerosis.

Keywords: CAD, PECAM-1, CD31, polymorphism, SNP

Inflammation and oxidative stress in Alzheimer's disease: therapeutic implications

Authors: C. Caruso, C.R. Balistreri, G. Candore, G. Colonna-Romano, D. Di Bona, G. Duro, D. Lio, F. Listì, G. Scapagnini, S.Vasto

Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative inflammatory disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and oxidative stress. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Abeta, product of cleavage of a much larger protein, the beta-amyloid precursor protein (APP) and neurofibrillary tangles.

Keywords: Alzheimer's disease, inflammation, pharmacogenomic, curcumin,

Decreased numeric density of succinic dehydrogenase positive mitochondria in CA1 pyramidal neurons of 3xTg-AD mice

Authors: P. Fattoretti, M. Balietti, T. Casoli, B. Giorgetti, G. Di Stefano, C. Bertoni-Freddari, F. Lattanzio, S.L. Sensi

We employed the preferential copper ferrocyanide staining method to investigate neuronal mitochondrial metabolic competence in an animal model of Alzheimer's disease (AD). To that aim, we studied the appearance of signs of mitochondrial dysfunction in triple transgenic mice (3xTg-AD) that express mutant forms of the amyloid precursor protein (APP), presenilin-1 (PS1), and tau protein.

Keywords: energy metabolism, succinic dehydrogenase, Alzheimer's disease, mitochondria, 3xTg-AD

QIMT by radio frequency (examination of tracking). Method of evaluation thickness of the intima media among patients having cardio vasclaires risk factors

Authors: X. Castellon, V. Bogdanova, J.C. Charniot

Method: QIMT by Radio frequency.Method of the examination used is in conformity with the IMT protocol of Mannheim standarts of normal values according to age, measurements of IMT based on the radio frequency. This study has been done with 150 patients(100 men and 50 women),aged between 45 and 60 years,having cardiovascular risk factors dyslipidemy,standard diabetes II noncomplicated, hypertension and tobacco).All patients having atheroma plaque located in the carotids have been excluded from the study.

Keywords: QIMT: calculation thickness of intima media, RF: radio frequency, IMT: thickness intima media, VIF: vasodilatation,

Analysis of endothelial function by radiofrequency coupled with two-dimensional echocardiography: the value of flow-mediated vasodilation. A study of 25 cases

Authors: X. Castellon, V. Bogdanova

Aim of the study: Endothelial dysfunction is an early indicator of cardiovascular disease which precedes clinical manifestations. The primary objective of the present study was to perform early-stage screening of patients presenting cardiovascular risk factors with endothelial dysfunction in order to optimise care provision. This will reduce the short- and medium-term occurrence of cardiovascular diseases.

Keywords: endothelial dysfunction, cardiovscular disease, radiofrequency, flow-mediated vasodilation, reactive hyper

Induction of morphological restoration of senescent

Authors: H. Choi, J.H. Rhim, S.J. Lee, K.A. Cho, S.C. Park

The Arg-Gly-Asp (RGD) peptide sequence is the cell attachment site of a large number of adhesive extracellular matrix as well as blood cells, and nearly half of the over 20 known integrins recognize this sequence. The biological effect of this peptide has been well studied for its influences on migration, growth and morphological changes especially concerning its impact on cancer cells. But its effect on senescent cells has not been thoroughly studied. We report here a novel aspect of RGD effect on the senescent phenotype.

Keywords: HDF, Human diploid fibroblasts, Replicative senescence, RGD, Arg-Gly-Asp

Isotope-Reinforced Polyunsaturated Fatty Acids Protect Yeast Cells from Oxidative Stress

Authors: K. Hirano, V. V. Shmanai, B. N. Marbois, R. Molinari, S. Morvaridi, M. Shchepinov, C. F. Clarke

Polyunsaturated fatty acids (PUFAs) are exquisitely sensitive to autoxidation damage. The autoxidation products include peroxyl and alky radicals, and small molecule aldehydes that form cross-links to other membrane components, or diffuse to other cellular sites and damage proteins and nucleic acids. Cells protect themselves from these autoxidation products by maintaining an arsenal of enzymes designed to keep reactive oxygen species in check, as well as a defensive system of small molecule antioxidants that terminate radical chain reactions.

Keywords: Isotope Effect, Lipid Autoxidation, Coenzyme Q, Ubiquinone, Fatty Acid

Combined chemical and brain stimulation induction of neurogenesis in brain injury and brain degeneration of aging.

Authors: M. Colgan, L.A. Colgan

Current science elucidates several consequences of normal metabolism within the neuron that partly determine aging damage to brain function; uncontrolled oxidation, chronic inflammation, and glycation. These consequences are influenced by several exogenous chemicals; R+ lipoic acid, acetyl-L carnitine, cytidine-diphosphate choline, N-acetyl cysteine, idebenone, docosahexaenoic acid, L carnosine, nicotine-adenine-dinucleotide hydrogen, turmeric, and salicylic acid, which may inhibit damage and facilitate neurogenesis.

Keywords: neurogenesis, fMRI, brain injury, senility, neuroimaging

Biomolecule PL1 immortalizes yeast in lethal stress conditions

Authors: H.R. Correia, S. Balseiro

It is generally assumed that all living beings die under specific and lethal stress conditions. However, here we show that a biomolecule called PL1, from one of the oldest known tree species, immortalizes yeast, the eukaryotic organism Saccharomyces cerevisiae, in fatal and combined oxidative and thermal stress conditions.

Keywords: Immortality, Yeast, Longevity, Lifespan, Lethal Stress

Selective autophagy: fueling and cleaning the aging cells

Authors: A.M. Cuervo

Autophagy is the intracellular process that mediates the digestion of cellular components in lysosomes. The autophagic system fulfills two major functions in mammalian cells, serving both as an alternative source of energy, when nutrients are scarce, and as an efficient mechanism for the removal of any intracellular damage structure. Autophagic activity has been described to decline with age in almost all organisms and tissues, as wells as in several age-related disorders.

Keywords: autophagy, protein homeostasis, lysosomes, protein aggregation, lipid metabolism

Intranasal delivery of cells to the brain

Authors: L. Danielyan, R. Schäfer, A. von Ameln-Mayerhofer, S. Verleysdonk, T. Klopfer, J. Geisler, M. Buadze, B. Proksch, G.H. Buniatian, C.H. Gleiter, W.H. Frey II

Organiser's Note: The presenter of this talk withheld their permission for video to be published.

Keywords: intranasal, non-invasive, delivery, stem cells, CNS

The first clinical transplantation of a tissue engineered airway

Authors: S.C. Dickinson, A.P. Hollander, S. Mantero, M.T. Conconi, M.A. Birchall, P. Macchiarini

The loss of a normal airway is devastating due to a lack of effective treatment methods for repairing large defects. However tissue engineering of an airway using a patient's own cells would create a complete, immunotolerant airway substitute. We therefore developed methods to bioengineer a tubular tracheal replacement and assessed the application of this technology in a patient with end-stage airway disease due to tuberculosis.

Keywords: Trachea Transplantation, Stem Cells, Tissue Engineering, Cartilage, Bioreactor

Organ Engineering by Bioprinting

Authors: G. Forgacs, C. Norotte, F. Marga

The general model of most tissue-engineering strategies rests on the use of exogenous biocompatible scaffolds in which cells can be seeded and matured in vitro or in vivo, to grow the tissue of interest. Scaffolds have been subject to prolific research and development over the last thirty years and, in general, offer the advantage of good biocompatibility, cell attachment and proliferation, while providing the biological, chemical, and mechanical clues to guide the eventual cell differentiation and assembly into a three-dimensional tissue construct.

Keywords: tissue engineering, scaffold, bioprinting, vascular graft, nerve graft

MicroRNA-regulated protein-protein interaction networks: how could they help in searching for pro-longevity targets?

Authors: R. Tacutu, A. Budovsky, V.E. Fraifeld

In spite of enormous efforts and accumulated knowledge, our capabilities for tackling aging and age-related diseases (ARDs), and ultimately to promote longevity are still very modest. What is lacking -- essential data on key players, efficient analytic tools, or both? Here we discuss how the existing data may be integrated and analyzed in the context of miRNA-regulated protein-protein interaction networks.

Keywords: longevity, aging, age-related diseases, networks, RNA interference

A highly sensitive diagnostic assay for early diagnosis of Alzheimer's disease

Authors: S.A. Funke, L. Wang, E. Birkmann, F. Henke, O. Bannach, P. Görtz, C. Lange-Asschenfeldt, D. Willbold

Organiser's Note: The presenter of this talk withheld their permission for video to be published.

Keywords: Alzheimer's disease, amyloid-beta, aggregate detection, early-diagnosis,

Systems Biology of Human Aging - Network Model 2009

Authors: J.D. Furber, P. Langley

The many observable signs of human senescence have been hypothesized by various researchers to result from several primary causes. Close inspection of the biochemical and physiological pathways associated with age-related changes and with the hypothesized causes reveals several parallel cascades of events that involve multiple interactions and feedback loops. We present a network diagram to aid in conceptualizing the many processes and interactions among them, including promising intervention points for therapy development.

Keywords: Systems Biology, Aging Network, Biochemistry, Physiology

Extracellular Aging: Issues for Therapy Design

Authors: J.D. Furber

Extracellular matrix (ECM) ages by several distinct mechanisms. This overview introduces the principal pathways and explores promising avenues for future therapy development. Pathways include: inflammatory glycoxidation and lipoxidation adducts: glycation crosslinks; amyloid deposits; protein residue isomerization, deamidation, and oxidation; fragmentation of collagen, elastin, laminin, and fibronectin; and loss of integrin binding sites. Promising future therapies could include drugs and enzymes that chemically repair the ECM, or cell therapies that biologically repair it.

Keywords: Extracellular matrix, integrin, glycation, elastin, cell therapy

Acetyl-L-carnitine supplementation to old rats prevents the age-related soleus muscle mitochondrial decay by activating mitochondrial biogenesis

Authors: V. Pesce, F. Fracasso, P. Cassano, M. Calvani, L. Mosconi, P. Cantatore, M.N. Gadaleta

Decay of mitochondrial function is a major contributor to aging process, particularly for those post-mitotic tissues like skeletal muscle heavily dependent on oxidative metabolism (e.g. soleus). Aim of this study was to test if long-term ALCAR supplementation to aged rats was able to activate mitochondrial biogenesis in soleus muscle.

Keywords: acetyl-l-carnitine, soleus muscle, mitochondrial biogenesis, aging,

Demographic consequences of defeating aging

Authors: L.A. Gavrilov, N.S. Gavrilova

A common objection against starting a large-scale biomedical war on aging is the fear of catastrophic population consequences (overpopulation). This fear is only exacerbated by the fact that no detailed demographic projections for radical life extension scenario were conducted so far. What would happen with population numbers if aging-related deaths are significantly postponed or even eliminated? Is it possible to have a sustainable population dynamics in a future hypothetical non-aging society?

Keywords: demographic projections, overpopulation, cohort-component method, war on aging, http://longevity-science.blogspot.com/

Search for mechanisms of exceptional human longevity

Authors: N.S. Gavrilova, L.A. Gavrilov

Studies on exceptional human longevity may provide important clues on possible factors and mechanisms that delay human aging and promote healthy life span. This epidemiological approach to unraveling the mechanisms of human aging and longevity is applied in this study using two different datasets.

Keywords: human longevity, maternal age, body build, farming background, fertility

Activating SIR Genes with the Cassava Root.Diet

Authors: V.K. Golay

It is well known among researchers that the SIR genes are activated by the sensing of low NADH relative to NAD a measure of cellular redox state in animals from yeast to mammals. I have found that a mono-food high cyanogenic cassava root diet will produce low NADH levels as soon as all other nutrition clears the large intestine in 5-7 days. Other survival genes may also be activated when the large intestine becomes clear of bacteria, fat, iron and high protein as the large intestine is central to other longevity gene signaling involving nutrient sensing.

Keywords: cassava, cyanogenic glucosides, NADH reduction, SIRT1-7 activation, iron chelation

Evolution of anticancer mechanisms in short- and long-lived species

Authors: A. Seluanov, C. Hine, M. Bozzella, A.A. Ribeiro, K.C. Catania, D.C. Presgraves, V. Gorbunova

In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anti-cancer mechanism that limits cell proliferation.

Keywords: Aging, cancer, telomerase, ,

An automated method of performing neuropsychological tests in studying gustatory reward circuitry.

Authors: A.M. Gouw, S.A. Garan, W. Freitag, J.D. Woolley

Dementia is prevalent in the aging population. Several studies have suggested a possible link between, limbic system anomalies and reward circuitry impairment in several forms of dementia. There are several difficulties in performing behavioral tasks with some patients due to the presence of the test administrator. Human interactions may alter patients' behavior. Thus, we have built and designed an Automated Memory Evaluation System (AMES) that measures the ability to remember geometric shapes of different colors and rewards positive patient responses as well as records response timings.

Keywords: dementia, neuropsychology, gustatory, reward, automated

Merging senescence with cellular dedifferentiation

Authors: M. Damri, H. Ben-Meir, Y. Avivi, V. Caspi, M. Wolfson, V. Fraifeld, G. Grafi

Dedifferentiation signifies the capacity of somatic cells to acquire stem cell-like properties. This process characterizes the transition of differentiated plant cells to protoplasts (plant cells devoid of cell walls), a transition accompanied by widespread chromatin decondensation. Transcriptome profiling of dedifferentiating cells revealed striking similarities with senescing cells; both display a large increase in the expression of genes of specific transcription factor (TF) families including ANAC, WRKY, bZIP and C2H2.

Keywords: Dedifferentiation, stem cell, senescence, chromatin, plants

DNA methylation in aging mice

Authors: S. Gravina, J. Vijg

Epigenetic regulation is critically important in mammalian development. Changes in epigenetic regulation have also been shown to play a role in the etiology of human disease, for example, hypermethylation of tumor suppressor genes in cancer. Epigenetic changes in aging, which have been studied much less frequently, are a concern because once established epigenetic profiles are only partially stable and can vary substantially as compared with the more static DNA sequence code.

Keywords: Aging, epigenetics, DNA methylation, ,

New Strategies for Enzyme Therapy for Lysosomal Storage Diseases

Authors: J.H. Grubb, C. Vogler, W.S. Sly

Enzyme replacement therapy (ERT) is an established means of treating lysosomal storage diseases. Infused therapeutic enzymes are normally targeted to the lysosomes of affected cells by interactions with cell-surface receptors that recognize carbohydrate moieties, such as mannose and mannose 6-phosphate (M6P), on the enzymes. We have investigated alternative strategies to deliver lysosomal enzymes to lysosomes using the lysosomal enzyme B-glucuronidase (GUS) and the enzyme deficient Mucopolysaccharidosis Type VII (MPS VII) mouse model,

Keywords: lysosomal storage disease, enzyme replacement therapy, MPS VII, ,

Deceptively simple - considerations regarding C. elegans lifespan, ageing and antioxidant studies

Authors: J. Gruber, S.K. Poovathingal, L.F. Ng, B. Halliwell

The nematode worm Caenorhabditis elegans (C. elegans) is increasingly popular as a model organism for ageing studies as well as for testing antioxidants and other compounds for effects on longevity. Not surprisingly, new investigators in the field (including ourselves) have begun to use C. elegans in this way. However, results in the literature are often confusing and contradictory. Here we discuss aspects that make C.

Keywords: Caenorhabditis elegans, antioxidant, screening, lifespan,

Origins of age-related DNA damage and dietary strategies for its reduction

Authors: P. Grúz, M. Shimizu, Y. Usui

Accumulation of DNA damage due to failing repair with advancing age is one of the key molecular pathologies in aging. Lipid peroxidation is a main source of endogenous damage in tissue DNA and is linked to chronic inflammatory processes underlying numerous degenerative diseases. Polyunsaturated fatty acids (PUFAs) are the direct source of this damage. Various PUFAs with different oxidizability are present as basic building blocks in biological membranes and serve as precursors for local signaling molecules which modulate the strength of immune response, growth and tissue maintenance.

Keywords: lipid peroxide, DNA damage, PUFA, ,

Mitochondrial translocation in young and old cells

Authors: A. Hallén

The mitochondria are constantly translocated along microtubule chains to locations in the cytoplasm where nutrients (triglyceride droplets, puryvate) are available. How the mitochondrion is directed is not known. A hypothesis is that it is transported by fluid movements to locations with a higher osmotic pressure. When a mitochondrion has absorbed puryvate and phosphate ions, the local osmotic pressure in the cytosol around the mitochondrion is decreased.

Keywords: Aging, Mitochondria, , ,

Phase I study of Seneca Valley Virus (SVV-001), a replication competent oncolytic virus, in patients with neuroendocrine (NE) cancers

Authors: P. Hallenbeck, K. Burroughs, S. Police, B. Brandenburg, D. Loesch, J. Stephenson, J. Nemunaitis, J. Poirier, C. Rudin

SVV-001 is a native non-pathogenic picornavirus that has exquisite tumor selectivity and therapeutic potential for cancers with neuroendocrine features, such as small cell lung cancer, carcinoid cancer, and most solid pediatric oncologies (Reddy et al., 2007; Wadhwa et al., 2007; Hales et al., 2008; Venkatraman et al., 2008). NTX-010 has many of the ideal properties of an oncolytic virus, including the lack of neutralizing activity by human blood, small size enabling efficient penetration and spread in tumors, stability, and ease of manufacturing.

Keywords: lung, cancer, oncolytic, seneca, pediatric

Expression of anti-fibrogenic factor, 14-3-3 sigma in active and senescent skin cells, both in vitro and in vivo

Authors: R. Hartwell, A. M. Rezakhanlou, A. Papp, M. Carr, A. Ghahary

Non-healing and chronic wounds affect 47 million patients each year in North America, a majority of whom are elderly. Wound healing is a complex and dynamic process that involves not only cell-cell communication in the form of signaling mediators, but also cell-matrix signaling. There is compelling evidence that an imbalance in any of these signaling events will lead to problematic healing.

Keywords: Non-healing wounds, 14-3-3 sigma, HIF-1, extracellular matrix, scarring

Differentiation of mouse adult bone marrow derived stem cells towards microglia

Authors: A. Hinze, A. Stolzing

Background: Microglia are the phagocytes of the brain. They have been implicated in the underlying causes of several degenerative diseases and display a loss of function and loss of balanced regulation during age. Microglia are thought to originate from special progenitor cells during embryogenesis and from myeloid progenitor cells migrating from bone marrow to the brain. Throughout life microglia are replenished at a slow rate both by limited proliferation of resident microglia and by the continuous migration of bone marrow derived progenitor cells.

Keywords: microglia, neurodegenerative diseases, aging, differentiation, cell therapy