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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.

Vascular ageing: causes, mechanisms, complications and possible therapeutic strategies

Authors: Balistreri CR, Candore G, Colonna-Romano G, Forte GI, Benedetto F, Spinelli F, Ruvolo G, Caruso C, Lio D.

Ageing is increasingly considered as an independent factor for the development of cardiovascular diseases (CDs). During ageing, there are structural and functional changes in the vasculature, including dilated lumen, altered intimal-medial thickness, vascular stiffness, endothelial dysfunction, increased endothelial apoptosis, matrix metalloproteinase dysregulation, increased expression of inflammatory molecules, aggravated oxidative stress and shortened telomere length.

Keywords: ageing, vascular ageing , cardiovascular diseases, new therapeutic strategies

TLR2 and age-related diseases: potential effects of Arg753Gln and Arg677Trp polymorphisms in acute myocardial infarction

Authors: C.R. Balistreri, G. Candore, F. Listi, M.P. Grimaldi, E. Incalcaterra, M. Caruso, E. Hoffmann, G. Colonna-Romano, D. Lio, C. Caruso

Inflammation is a key mechanism in the onset of age-related diseases. Variations in genes encoding molecules involved in inflammatory responses may therefore influence the risk for age-related diseases, as atherosclerosis, possibly through interaction with chronic infections and pro-inflammatory environmental risk factors such as smoking, diabetes and obesity. The TLR2 and TLR4 genes, both involved in the inflammatory process, are potential candidates and TLR4 has been previously associated with cardiovascular disease, although other studies have failed to confirm this.

Keywords: inflammation, atherosclerosis, AMI, TLR2,

Can the blood leukocyte telomere length predict sporadic thoracic aortic aneurysm?

Authors: C.R. Balistreri, C. Caruso, C. Pisano, G. Bianco, K. Fattouch, M. Caruso, E. Maresi, G. Ruvolo, G. Candore

The prevalence of cardiovascular diseases (CVD) rises with ageing and is one of the main causes of mortality in Western countries. In view of the progressive population ageing, there is an urge for a better understanding of age-associated diseases, such as sporadic thoracic aortic aneurysm (S-TAA), and their underlying molecular mechanisms. Several cardiovascular risk factors (i.e. hypertension, oxidative stress, smoking, etc.) seem to explain most of risk of S-TAA in general population. However, little is known about its precise cellular, molecular mechanisms and genetic determinants.

Keywords: S-TAA, biological ageing, mean blood leukocyte telomere length, ,

Effect of Dehydroepiandrosterone and Related Steroids on Neurogenesis in Adult Rat Brain

Authors: Z. Bandpey, J. Herbert

Most neurons in adult central nervous system (CNS) are terminally differentiated and are not replaced when they die. Evidence now exist that small populations of neurons are formed in the adult olfactory bulb and hippocampus. In adult hippocampus, newly born neurons originate from putative stem cells that exist in the subgranular zone of the dentate gyrus. Progeny of these putative stem cells differentiate into neurons in the granular layer within a month of the cells birth, and this late neurogenesis continues throughout the adult life of all mammals.

Keywords: neurogenesis, hippocampus, DHEA, 7-OXO-DHEA ,

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, ,

Oxygen Radicals and Aging

Authors: G. Barja
Audio: (Audio) (Slides)

Reactive oxygen species (ROS), continuously generated in the mitochondria of healthy post-mitotic tissues, are thought to contribute significantly to aging. Studies from our laboratory dealing with the relationship between oxidative stress and aging will be presented. ROS can damage cellular lipids, proteins and, most importantly, DNA. Although antioxidants help to control oxidative stress in cells in general, they do not increase the maximum life span of mammals and their levels are lower in long-lived than in short-lived animals.

Keywords: aging, oxygen radicals, DNA damage, caloric restriction, Ames dwarf mice

Accelerating translational research processes from bench to clinic

Authors: Barker RW.

The productivity of medical innovation has been in decline, and this threatens the commitment of both public and private funders. However, there are both disruptive technologies and disruptive ideas that promise a turnaround. CASMI (www.casmi.org.uk) is exploring both, and developing testable models for change - including new open innovation-based discovery models, adaptive licensing of medicines, the use of real world data in development, and the personalisation of therapy on both genomic and behavioural grounds.

Keywords: CASMI, Adaptive licensing, Open innovation, Real world data, Cell therapy

Cellular Nutrient Sensing and Longevity

Authors: N. Barzilai, L. Rossetti, M. Brownlee, M. Hawkins, J. Crandall
Audio: (Audio) (Slides)

Caloric restriction (CR) life span of animals, while in humans excess nutrient intake is associated with the "syndrome of insulin resistance". This syndrome represents a constellation of metabolic defects that are important risk factors for age-related diseases. Under normal circumstances, the deleterious effects of the excessive availability of nutrients are countered by the prompt activation of nutrient "counterregulatory" systems. The latter include (but is not limited to) hypothalamic neuro-circuitries partly under the control of leptin.

Keywords: caloric restriction, nutrient sensing, hexosamine biosynthetic pathway, longevity, aging

Treating age-related macular degeneration through enhanced lysosomal degradation of A2E

Authors: Beliakoff G, Yogalingam G, Goldin E.

Age Related Macular Degeneration (AMD) is the leading cause of visual loss among people 65 years and older. This disease manifests into two distinct forms, wet and dry. The pathogenesis for both forms is poorly understood and numerous hypothetical models have been studied to better understand their mechanism. The dry form of AMD involves atrophy of the retinal pigment epithelium (RPE) by the accumulation of bisretinoid lipofuscin within lysosomes as the cells phagocytose the outer membranes of the photoreceptors.

Keywords: age-related macular degeneration, AMD, lipofusin, A2E, retinal pigmented epithelium

Comparative estimation of adaptation biomarkers

Authors: L.M. Belozerova

The decrease of organism adaptive possibilities in aging is best reflected in reduction of mental and physical working capacity.

The aim of the research is to comparative analysis of three biological age determination methods by mental, physical and both kinds of working capacity and measurement of sex differences in age changes rate.

Keywords: mental and physical working capacity, biological age, , ,

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

Poly(ADP-Ribosyl)ation and Telomere Dynamics in Mammalian Cells

Authors: S. Beneke, P. Boukamp, A. Bürkle

We have previously described a positive correlation between poly(ADP-ribosyl)ation capacity of mononuclear blood cells with longevity of mammalian species. Our comparison of purified recombinant human and rat PARP-1 revealed that this correlation might be explained in part by evolutionary sequence divergence. We have also developed molecular genetic approaches to modulate the poly(ADP-ribosyl)ation status in living cells.

Keywords: Poly(ADP-ribosyl)ation, Telomere, Inhibition , ,

ALTernative ways to immortality. blessing or curse?

Authors: W. Berger

Cellular immortalization obtained by activation of telomere stabilisation mechanisms is believed to be essential for development of human cancer. This implies that inhibition of such mechanisms should represent an ideal strategy in cancer therapy. In most cases, tumour cells activate the telomere-elongating enzyme telomerase during malignant progression. Consequently, several experimental therapy approaches focus on targeting telomerase.

Keywords: telomere stabilisation mechanisms, lung cancer, glioblastoma, ALT, telomerase

Mitochondrial gene transfer to transplantable tumours lacking a mitochondrial genome

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

Mammalian cells contain multiple mitochondria with each mitochondrion containing several genomes. With few known exceptions, mitochondria are retained within their cell of origin. Nevertheless, intercellular mitochondrial transfer via membrane nanotubes has been demonstrated in cell culture systems in vitro and recent phylogenetic evidence has indicated that mitochondrial gene transfer from host to tumour cells occurs in a canine transmissible venereal tumour (Rebbeck et. al., Science 331: 303 2011). Intercellular mitochondrial gene transfer has not been demonstrated physiologically.

Keywords: mitochondrial genome, tumorigenesis , metastasis, cell metabolism, horizontal gene transfer

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

Decay of mitochondrial metabolic competence in the aging cerebellum

Authors: C. Bertoni-Freddari, P. Fattoretti, B. Giorgetti, M. Solazzi, M. Balietti

Cytochrome oxidase (COX) activity, selectively evidenced by preferential diaminobenzidine cytochemistry, has been measured by computer-assisted morphometric methods in the cerebellar cortex of adult and old rats. We calculated the ratio (R) between the area of the precipitate due to the cytochemical reaction and the overall area of each mitochondrion. The value of R is reported to provide information on the fraction (%) of the inner mitochondrial membrane actively involved in adenosine triphosphate (ATP) provision.

Keywords: mitochondrial metabolic competence, cerebellum, mitochondrial size, megamitochondria, cytochrome oxidase activity

Cytochrome oxidase activity in hippocampal synaptic mitochondria during aging: a quantitative cytochemical investigation

Authors: C. Bertoni-Freddari, P. Fattoretti, B. Giorgetti, M. Solazzi, M. Balietti

An impaired energy metabolism is reported to represent a critical condition contributing to physiological aging and predisposing to age-related pathologies. With specific reference to nerve cells, actual and adequate energy provision is a necessary prerequisite for brain performances, thus any alteration affecting the neuronal energy supply machinery may constitute a potential threat for derangements in cell-to-cell communication. To asses the mitochondrial metabolic competence, i.e.

Keywords: mitochondrial metabolic competence, synaptic mitochondria, cytochrome oxidase activity, hippocampus, morphometry

Selective decline of the metabolic competence of oversized synaptic mitochondria in the old monkey cerebellum

Authors: C. Bertoni-Freddari, M. Balietti, B. Giorgetti, Y. Grossi, T. Casoli, G. Di Stefano, G. Perretta, P. Fattoretti

The morphofunctional features of synaptic mitochondria positive to the activity of cytochrome oxidase (COX) were investigated in the cerebellar cortex of adult and old monkeys to seek alterations of the energy metabolism specifically occurring at the neuronal synaptic compartment with advancing age. Numeric density (Nv), volume density (Vv) as well as average volume (V) and average length (Fmax) were the mitochondrial ultrastructural parameters measured by computer-assisted morphometric methods.

Keywords: mitochondrial metabolic competence, monkey, cytochrome oxidase, megamitochondria, cerebellum

Decreased presence of perforated synapses in a triple-transgenic mouse model of Alzheimer's disease

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

Transgenic mouse models of Alzheimer's disease (AD) are useful systems for understanding the genotype-phenotype interaction involved in this pathology. The innovative 3xTg-AD (APP/Tau/PS1) mouse model closely mimics the AD pathogenetic process as it develops clinically relevant pathological hallmarks, i.e. both neuritic A-beta plaques (by 6 months of age) and tangles (by 10-12 months of age).

Keywords: perforated synapses, triple-transgenic mouse, Alzheimer disease, morphometry, hippocampus

Synaptic pathology in the brain cortex of old monkeys as an early alteration in senile plaques formation

Authors: C. Bertoni-Freddari, P. Fattoretti, T. Casoli, G. Di Stefano, B. Giorgetti, Y. Grossi, M. Balietti, G. Perretta

Senile plaques (SP) are alterations of the senile brain particularly prominent in Alzheimers disease (AD). The classical plaque appears as a roughly spherical area in the neuropil consisting of a compact core or of narrow bundles of beta amyloid (bA), between abnormal neurites. Although SP formation is reported to occur over years, in the human brain this process can be studied only at autopsy and this constitutes a great limit to obtain results specifically regarding the steps of SP build up.

Keywords: Plaques, Synapses, Morphometry, Alzheimer disease, Macaca fascicularis

Cytochemical estimation of cytochrome oxidase activity as a morphofunctional mitochondrial check up

Authors: C. Bertoni-Freddari, P. Fattoretti, T. Casoli, G. Di Stefano, B. Giorgetti, Y. Grossi, M. Balietti

A growing body of experimental results is supporting the critical role played by mitochondrial damage in physiological aging and age-related pathologies. This clear awareness has prompted the need of checking the functional state of mitochondria in order to plan adequate intervention strategies to counteract mitochondrial dysfunctions. In this context, the activity of cytochrome oxidase (COX) is presently considered as a reliable marker of neuronal metabolism.

Keywords: Mitochondrial metabolic competence, Cytochrome oxidase, Megamitochondria, COX cytochemistry, Mitochondrial morphometry

Testing mitochondrial metabolic competence by cytochrome oxidase preferential cytochemistry vs. immmunoreactivity of subunit I and IV

Authors: P. Fattoretti, C. Bertoni-Freddari, T. Casoli, G. Di Stefano, B. Giorgetti, Y. Grossi, M. Balietti

Cytochrome oxidase (COX), complex IV of the mitochondrial respiratory chain, is composed of 13 subunits: three encoded by mitochonmdrial DNA (mtDNA) and ten encoded by nuclear DNA. The coordinated expression of both genomes constitutes an early step in the synthesis of the COX enzyme complex, conceivably quantitative estimations of the level of expression of COX subunits may provide clues to identifying precocious alterations of mitochondrial dysfunction.

Keywords: Mitochondrial metabolic competence, Cytochrome oxidase, COX subunit I, COX subunit IV, COX immunohistochemistry

Level and distribution of microtubule associated protein-2 (MAP2) as an index of dendritic structural dynamics

Authors: G. Di Stefano, T. Casoli, P. Fattoretti, M. Balietti, Y. Grossi, B. Giorgetti, C. Bertoni-Freddari

In the fully differentiated adult central nervous system (CNS) neuronal processes need to maintain a fine balance between stability and plasticity. In addition to being very plastic to adapt to the changing environmental stimulation, neuronal wiring diagrams must be also sufficiently stable to accomplish specific functional tasks on which they are tuned. In this dynamic status, the neuronal cytoskeleton and its components (actin filaments, neurofilaments and microtubules together with the respective associated proteins) are reported to play a major and critical role.

Keywords: MAP2, Dendritic structural dynamics, CNS plasticity, Hippocampus, Olfactory bulb

Structural synaptic remodelling in the perirhinal cortex of adult and old rats following object-recognition training

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

A computer-assisted morphometric study has been carried out on the synaptic junctional areas of perirhinal cortex isolated from adult (4-6 month-old) and old (25-27 month-old) Wistar rats exposed to an object-recognition training. The paradigm consisted of 6 sessions in which the animals could explore two identical objects. Rats were divided into the following groups: trained animals: adult trained (AT) and old trained (OT); untrained animals: adult control (AC) and old control (OC).

Keywords: Synaptic plasticity, Object-recognition test, Perirhinal cortex, E-PTA, Synaptic morphometry

Evidence that cryonics may work

Authors: B.P. Best

Deep hypothermia can result in reversible arrest of neurological activity. The anatomical basis of mind is preserved much longer than six minutes in the absence of oxygen. Cryogenic vitrification can potentially preserve the anatomical basis of mind for many thousands of years. If future science is capable of rejuvenation, then future science should also be capable of reviving, curing and rejuvenating humans who were cryopreserved using cryonics technologies.

Keywords: cryonics, rejuvenation, vitrification, ischemia, future

Vascular and Neuronal Damage in Cryonics Patients

Authors: B.P. Best

Cryonics patients can suffer varying degrees of ischemic damage, including both warm and cold ischemia. Although efforts to minimize warm ischemic damage for cryonics patients are often successful, most cryonics patients suffer lengthy cold ischemia during shipment in water ice to a cryonics facility for cryoprotectant perfusion. Vascular damage due to ischemia impedes perfusion with cryoprotectant solutions intended to eliminate ice formation.

Keywords: cryonics, ischemia, edema, vascular, damage

Damage Assays Rather than Biomarkers of Aging

Authors: B.P. Best

Damage Assays Rather than Biomarkers of Aging Aging is multiple forms of damage. Aging is primarily damage to macromolecules: proteins, lipids, carbohydrates, mitochondrial DNA and nuclear DNA (including telomeres). Aging damage is primarily due to ROS, RNS, sugars (glycation), radiation, pathogens, inflammatory cytokines, and accumulated toxins (metals, PCBs, dioxins, etc.). There is no singular aging process, but each species can be characterized by a maximum lifespan.

Keywords: aging, biomarkers, damage, assays, rejuventation

Kinetics of AGE-formation on BSA with various reducing sugars and dicarbonyl compounds in equimolar ratios

Authors: L. Luers, K. Rysiewski, C. Dumpitak, D. Willbold, E. Birkmann

Reducing sugars or reactive dicarbonyl compounds play a major role in glycation of proteins in vivo. Glycation of proteins is the first step in a non-enzymatic reaction resulting in advanced glycation endproducts (AGEs). AGEs can change the biological activities or even inactivate proteins [1; 2; 3]. AGEs formed by reducing sugars are also able to crosslink proteins leading to insoluble aggregates. Therefore it is important to understand the mechanism of AGE-formation.

Keywords: advanced glycation endproducts (AGEs), kinetics, reducing sugars, methylglyoxal, glyoxal

A highly sensitive diagnostic assay for aggregate-related diseases e.g. prion diseases and Alzheimer's disease

Authors: E. Birkmann, S.A. Funke, F. Henke, D. Willbold, D. Riesner

In many neurodegenerative diseases e.g. Prion Diseases, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, protein aggregates are formed in the very beginning or in the progress of disease. Up to now it is not known, if these aggregates are causative or symptoms in the different diseases, but many studies show, that the aggregates or even oligomers of the according proteins are neurotoxical and therewith a reason of neurodegeneration.

Keywords: neurodegenerative diseases, diagnostic assay, aggregate-related diseases, prion diseases, Alzheimer's disease

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,

Computer Simulation of Telomere Dynamics and Senescence

Authors: K.B. Blagoev, E.H. Goodwin

In normal human somatic cells, telomeres become shorter with each cell cycle until their chromosome end protection function fails causing the cells to senesce. Previously telomere loss was thought to be gradual, and the approach to cellular senescence was likened to a mitotic clock in which the shortest telomere of a progenitor cell determined the maximum number of cell doublings. In addition to the basal loss, recent evidence indicates that there are occasional large gains, losses and exchanges of telomeric DNA collectively called telomere dynamics.

Keywords: modeling, telomere dynamics, Monte Carlo , ,

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

Telomeres and human disease: a matter of bad ends

Authors: M.A. Blasco
Audio: (Audio)

Telomeres are chromosome end-capping structures, which protect the chromosome ends from unscheduled DNA repair and degradation. Telomeres are composed of repetitive DNA (TTAGGG repeats) bound to an array of specialized proteins. The length of telomere repeats and the integrity of telomere-binding proteins are both important for telomere protection. In addition, telomeres are regulated by a number of epigenetic modifications, thus pointing to a higher-order control of telomere length and function.

Keywords: telomeres, stem cells, cancer, aging, TRF2

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,

Demonstration of differences in the action of several metabotropic and ionotropic glutamate agonists on intracellular reactive oxygen species and the Na-pump

Authors: A. Boldyrev, E. Bulygina, D. Carpenter, W. Schoner

Two glutamate receptor agonists, NMDA (N-methyl-D-aspartic acid) and ACPD (cis-(1S/3R)-1-aminocyclopentane-1,3-dicarboxylic acid) increase the reactive oxygen species (ROS) level in rat cerebellum granule cells whereas the third one, 3-HPG (3-hydroxyphenylglycine) decreases this parameter. The simultaneous presence of 3-HPG together with NMDA or ACPD prevents the generation of ROS by neuronal cells. A similar effect of these ligands on Na/K-ATPase was demonstrated: NMDA and ACPD inhibited the enzyme activity but 3-HPG activated Na/K-ATPase and prevented its inhibition by NMDA or ACPD.

Keywords: glutamate receptors, reactive oxygen species, Na-pump , ,

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

Combining data from evolutionarily distant species to predict long-lived mutants

Authors: B. Borgeson, C. St-Jean-Leblanc, E.M. Marcotte

Huge portions of the genomes of even the most well-studied organisms remain poorly understood. Accordingly, computational methods have attempted to predict functions and phenotypes associated with genes. Previously, our lab has constructed so-called functional networks--networks designed to predict the function of genes based on their similarity to other genes on a number of biological measures--and used these networks to show that even complex phenotypes such as longevity are relatively predictable.

Keywords: bioinformatics, networks, lifespan, ,

Differentiation of radial glia cells into astrocytes is a possible ageing mechanism in mammals

Authors: O.G. Boyko

In one's time O.M. Ivanova-Kazas supposed that the senescence phenomenon can be understood only by comparison of design of primitive ageless animals with senescent forms. At comparison of ageless vertebrates forms (some fishes, tortoises, etc.) with mammals among which ageless species do not occur, it became clear that the generation of neuroblasts in adult/ embryonic phenotypes at vertebrates and the sites of their ultimate localization are disconnected.

Keywords: aging, mammals, astrocytic hypothesis, radial glial fibres,

The role of airway Clara cell senescence in the pathogenic mechanism of COPD

Authors: Bracha S, Sagiv A, Krizhanovsky V.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation that is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. The chronic airflow limitation characteristic of COPD is caused by a mixture of small airways disease (obstructive bronchiolitis) and parenchymal destruction (emphysema). Besides cigarette smoke, aging is a major risk factor for COPD.

Keywords: COPD, Senescence, p53, Lung, Mouse

Current and Future Stategies for the Treatment of Metabolic Storage Disorders

Authors: R.O. Brady
Audio: (Audio) (Slides)

Following the unprecedented success of enzyme replacement therapy (ERT) in patients with Type 1 (non-neuronopathic) Gaucher disease, this therapeutic approach has been applied to a number of other hereditary metabolic storage disorders of humans. I shall discuss the responses to ERT in patients with Fabry disease, Hurler disease, Maroteaux-Lamy disease and Pompe disease. Because impairment of the central nervous system does not improve with ERT alone, additional therapeutic modalities have been initiated to treat patients with brain involvement.

Keywords: Enzyme replacement, substrate reduction, chaperone , ,

Aging brain mitochondrial dysfunction: metabolic rejuvenation

Authors: G.J. Brewer

Numerous reports document the decline in various aspects of mitochondrial function with physiological aging as well as the pathologic aging seen in Alzheimer’s disease, but remains unclear whether these deficits are the immediate response to an aging environment and the degree of their reversibility. By isolating neurons from the brains of rats and mice across the age-span and culturing them in a uniform environment, we eliminate the confounds of aging hormonal, vascular and immune systems.

Keywords: brain, mitochondria, ROS, estrogen, epigenetics

The Struggle to Keep our Telomeres Long

Authors: Briggs LA.

One basic quality of human life is that every time our cells divide the tips of our chromosomes get shorter. This shortening of telomeres may be the molecular clock of aging. Indeed, the shortening of telomeres has been shown to be the trigger that induces senescence of human cells grown in culture; whether this can be extrapolated to include human organismal aging itself is not yet known. The correlation between telomere length and age is very strong and shorter telomeres directly correspond to shorter human life expectancy, but "cause and effect" are still debated.

Use of Trichinella Railliet 1895 vaccine for prevention and treatment of immune deficiencies

Authors: V. Britov, E. Nivin

Secondary immunodeficiency is widespread in developed countries. It is mostly caused by the lack in evolutionary-shaped antigenic stimulation of immunity. The marked decline in cellular immunity (which plays the main role in the structural homeostasis) results in increased autoimmune and degenerative diseases, chronic infections and cancer, and characterizes immune aging process.

Keywords: immunity, immunodeficiency, vaccine, trichinaelle,

Alternative lengthening of telomeres: a telomerase independent route to cellular immortality

Authors: D. Broccoli
Audio: (Audio)

The limited self-renewal capacity of most human cell types that contributes to aging is recapitulated in vitro by primary fibroblasts that undergo replicative senescence. Stabilization of telomeric repeat arrays is sufficient to bypass this process and confer the potential for unlimited cellular division. This cellular immortality is also critical for tumorigenesis, an escalating health problem as the average age of the population increases. Telomerase activation is the common mechanism used by stem cells and tumors for maintenance of telomeric DNA.

Keywords: alternative lengthening of telomeres, p53, recombination, telomerase ,

New limbs for old - lessons from the newt

Authors: J.P. Brockes
Audio: (Audio)

The urodele (tailed) amphibians such as the newts and salamanders are the champions of regeneration among adult vertebrates. An adult newt can regenerate its limbs and tail, upper and lower jaws, ocular tissues such as the lens and retina, as well as large sections of the heart. We tend to regard these animals as exceptional or exotic in respect of this property, but regenerative ability on this scale is widespread throughout metazoan phylogeny and it is usual to regard it as a basic attribute which is lost for reasons which are unclear.

Keywords: regeneration, urodele, heart, lens, plasticity

Growth hormone alters components of the glutathione metabolic pathway in dwarf mice

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

Reduced signaling of the growth hormone (GH)/insulin-like growth factor-1(IGF-1)/insulin pathway is associated with extended life span in several species. Ames dwarf mice are GH and IGF-1 deficient and live 50-64% longer than wild type littermates (males and females, respectively). Previously, we have shown that Ames mice exhibit elevated levels of antioxidative enzymes and lower oxidative damage.

Keywords: dwarf mice, glutathione, growth hormone , ,

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, ,

Testing the Free Radical Theory of Ageing in Bats

Authors: A.K. Brunet-Rossinni

The extended longevity of bats, despite their high metabolic rate, may provide insight to patterns and mechanisms of ageing. I tested the free radical theory of ageing as an explanation for the extreme longevity of the little brown bat, Myotis lucifugus (maximum lifespan potential "MLSP" = 34 yrs). In a comparative study, I measured whole-organism oxygen consumption and mitochondrial hydrogen peroxide production in brain, heart, and kidney tissues from M. lucifugus and short-tailed shrews, Blarina brevicauda (MLSP = 2 yrs). As predicted by the free radical theory of ageing, M.

Keywords: free radical theory, long-lived organism, bats , ,

Aging of cardiac myocytes and mitochondrial turnover

Authors: A. Terman, U.T. Brunk
Audio: (Audio) (Slides)

Aging preferentially affects postmitotic cells, such as cardiac myocytes and neurons, and is associated with intralysosomal lipofuscin accumulation and with oxidant-induced mitochondrial damage. Autophagy provides for continuous recycling of old and damaged mitochondria, and this process is hampered by lipofuscin deposition. To test whether age-related mitochondrial changes, including the formation of so-called 'giant' mitochondria, might originate from imperfect mitochondrial turnover, we inhibited autophagy in cultured neonatal rat cardiac myocytes with 3-methyladenine (3MA).

Keywords: aging, autophagy, cardiac myocytes, lysosomes, mitochondria

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