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.

Cryptobiosis, ageing and cancer: yin-yang balancing of signalling networks

Authors: Z. Huang, A. Tunnacliffe

On experiencing a persistent, severe and unavoidable stress, a cell or an organism will either establish a new equilibrium and continue to exist, or perish if it fails to do so. To overcome such unfavourable conditions, some organisms can tip the delicate balance to survival by entering cryptobiosis, a quiescent state in which metabolism essentially comes to a reversible standstill. The most well-known cryptobiosis is anhydrobiosis, which enables certain organisms to survive in the absence of water.

Keywords: ageing, anhydrobiosis, cancer, cell signalling, cryptobiosis

Patient-Specific Embryonic Stem Cells Derived from Human SCNT-Blastocysts

Authors: W.S. Hwang
Audio: (Audio)

Many human injuries and diseases result from defects in a single cell type. If defective cells could be replaced with appropriate stem cells, progenitor cells, or cells differentiated in vitro, it might be possible to treat disease and injury at the cellular level in the clinic, providing that immune rejection of transplanted cells could be avoided. By generating hESC from human NT-blastocysts in which the somatic cell nucleus comes from the individual patient, it might obviate the possibility of immune rejection if these cells were to be used for human treatment.

Keywords: , , , ,

Alzheimer's, Huntington's and Prion Diseases - why are misfolded proteins so interesting, but so destructive?

Authors: V.M. Ingram, B.J. Blanchard, A. Ahmad, L. Zhang, L. Rozeboom
Audio: (Audio)

A misfolded protein can lead to neurodegeneration when the new peptide or protein conformation acquires a new physiological activity that is deleterious to cells or to organelles. The amino acid sequence may be perfectly normal, but the new conformation has new properties. We become aware of these events, if the misfolded protein is harmful and causes a disease, a gain of (unwanted) function. Alzheimer's Disease. A current hypothesis holds that in this disease the Alzheimer peptides, Aß1-40 and especially Aß1-42, are overproduced from the precursor protein for one of several reasons.

Keywords: Alzheimer's, Huntington's, Prion, misfolded peptides,

Herpes simplex virus type 1 in brain and apolipoprotein E type 4 allele: a dangerous liaison for Alzheimer's disease.

Authors: R.F. Itzhaki, S. J. Shipley, C.B. Dobson, M.A. Wozniak
Audio: (Audio) (Slides)

Infectious agents have been proposed as factors in several chronic diseases, especially the age-associated ones, heart disease and Alzheimer's disease (AD). We have implicated herpes simplex virus type 1 (HSV1) in the aetiology of AD. We discovered, using solution PCR, that HSV1 DNA resides latently in brain of a high proportion of elderly people, and that in brain of carriers of the type 4 allele of the apolipoprotein E gene it confers a strong risk of AD (Itzhaki et al., 1997).

Keywords: Alzheimer's disease, herpes simplex virus type 1, apolipoprotein E, amyloid, inflammation

Oxygen free radicals production and DNA damage/repair activity in lymphocytes of elderly subjects

Authors: J. Jajte, J. Grzegorczyk, J. Błasiak, A. Sapota

Purpose: A growing body of experimental data indicates that increased levels of DNA damage is associated with aging process. It has been also hypothesized that reactive oxygen species play an important role in the aging and cellular senescence. The aim of our study was to examine the relationship between oxygen free radicals production and DNA damage/repair in lymphocytes with age and selective diagnostic parameters in elderly subjects.

Keywords: ROS, DNA damage, DNA repair, lymphocytes, elderly subjects

Abnormal Lysosomal Processing of Internalized Cholesteryl Esters In Macrophages

Authors: W.G. Jerome
Audio: (Audio) (Slides)

Progressive lysosomal dysfunction has been associated with aging. One cause of this dysfunction is build up of indigestible material within lysosomes and a resultant inhibition of lysosome function. In the case of lysosomal storage diseases with well characterized genetic defects, the link between defect and dysfunction is clear and usually occurs early in life. It is generally associated with mutations in particular enzymes responsible for lysosomal digestion of internalized or autophagic material.

Keywords: lysosome, cholesterol, atherosclerosis, pH,

Oxidized lipids in atherosclerotic macrophages: what role do they play in foam cell formation?

Authors: W. Jessup
Audio: (Audio)

Macrophages appear at a very early stage in the development of atherosclerosis and persist throughout evolution of the disease. Lipid-filled "foam cell" macrophages are an unusual and characteristic feature of atherosclerotic lesions. Foam cells contain massive intracellular deposits of neutral lipids, mainly cholesteryl esters (CE) and triglycerides. In early lesions the lipids are stored mainly as droplets in the cytoplasm but lysosomal lipid storage is also evident, particularly as the lesion progresses.

Keywords: macrophage, atherosclerosis, cholesterol, oxysterol, oxidation

Extracellular redox state: refining the definition of oxidative stress in aging

Authors: D.P. Jones
Audio: (Audio)

Oxidative stress in aging can result from an imbalance of prooxidants and antioxidants with excessive, destructive free radical chemistry. Thiol systems are important in the control of these processes both by protecting against the damage and serving in redox signaling mechanisms to sense the danger and repair the damage. Our studies show that the redox state of the central antioxidant, glutathione (GSH), can be quantified under clinical conditions and used as a quantitative index of oxidative stress.

Keywords: redox signaling, oxidative stress, glutathione, apoptosis, thioredoxin

Role of Insulin Action and Gene Expression in Adipose Tissue in Aging

Authors: C.R. Kahn, M. Katic, M. Bluher
Audio: (Audio)

Defects in the insulin signalling pathway in lower organisms, such as C. elegans and Drosophila, have been associated with increased longevity. Caloric restriction has also been shown to increase longevity in organisms ranging from yeast to mammals. To further explore these associations, we studied mice with a fat specific knockout of the insulin receptor (FIRKO mice), since they have reduced fat mass in the presence of normal or increased food intake and also have a selective defect in insulin action in adipose tissue.

Keywords: insulin receptor, oxidative phosphorylation, gene expression, adipose tissue ,

Manipulating the intracellular fate of an aggregate-prone protein

Authors: S. Kaushal
Audio: (Audio)

Like many inherited and acquired protein conformational diseases (PCDs), P23H opsin associated with Autosomal Dominant Retinitis Pigmentosa (ADRP) is largely a misfolded protein and retained within the cell. We had previously described a set of pharmacological chaperones, including the native chromophore 11-cis-retinal, that quantitatively promoted the in vivo folding and stabilization of P23H opsin. Like the wild-type (WT) protein, the rescued mutant formed pigment, acquired mature glycosylation, and was transported to the cell surface.

Keywords: , , , ,

Senescence as morbus reponibilis

Authors: A.V. Khalyavkin, A.I. Yashin

At the moment there is no conclusion on the origin of senescence. Recently the author of a telomere shrinkage hypothesis of aging has rejected it as explanation of an origin of aging and has put forward a new one (Olovnikov, Biochemistry 2003; Adv.Gerontol. 2003). On the other hand, one of the most commonly noted versions of the free radical theory of aging has also failed to explain non-pathological senescence (Orr, Sohal, Exp.Gerontol. 2003).

Keywords: aging plasticity, external influences, aging reversibility , ,

Statistical Issues of Regression Analysis on Development of an Age-predictive Equation

Authors: K. Kikkawa

INTRODUCTION: The ratio of biological age to chronological age could be used as the bio-marker of aging. In this study, several statistical information criteria in regression analysis were argued to establish the predictive equation of age from the measurements of simple fitness tests and other statistical issues.

Keywords: Regression Analysis, Prediction of Age, Fitness Test, Japanese ,

For a tree time can be slowed down: Analysis of proliferation capacity of tree cells

Authors: B. E. Flanary, G. Kletetschka

Time can (apparently) be slowed down for Pinus longaeva, a pine living on West coast of United States. Trees are found to be more than 3,000 years old and several are over 4,000 years old. The cells of these trees, as well as trees with normal life span, were extracted for telomere and/or telomerase activity.

Keywords: Longevity, Telomerase, Telomere, Trees, Pinus Longaeva

Soft Strategies for Postponing Ageing and Prolonging Human Life

Authors: Ü. Kristjuhan

Increasing diseases and mortality in old age may involve many different mechanisms. So to speak about age-related changes is often more exact. There are some soft strategies for postponing age-related changes. One strategy is based on the all-cause mortality studies. These studies refer to ways to postpone age-related changes through decreasing known risk factors of these changes. It is possible to use many data of epidemiological studies about different risk factors influencing all-cause mortality.

Keywords: strategies, postponing ageing, prolonging life, humans ,

Chaperones of longevity

Authors: J. Krøll

The inherent immirtality of the embryonic stem cells imply that replicative senescence as possibly aging and longevity are epigenetic phenomena, probably resulting from changes in the expression of relatively few regulatory genes. Among those it is suggested that emphasis is placed on the genes that determines the level of expression of the "housekeeping" molecular chaperones.

Keywords: molecular chaperones, longevity, aging, methylation, cancer

Revolutionizing Transgenesis and Gene Disruptions using P-element Transposition

Authors: J.W. Larrick
Audio: (Audio)

Transposable elements have become an indispensable tool for research in many organisms. The robust integration efficiency of the P element transposon has significantly enhanced the capabilities of Drosophila researchers. However, as the P element had been unable to integrate DNA outside of the Drosophilidae family, this efficient transposon system was unavailable for use in other organisms, until now. Modified P element sequences have been engineered to enable this transposon system to effectively integrate transgenes into a variety of cells in culture, ranging from avian to human.

Keywords: transposon, transgenic, knockout, gene, therapy

A-beta Immunotherapy: Lessons From Mice, Monkeys and Men

Authors: C.A. Lemere, M. Maier, T.J. Seabrook
Audio: (Audio) (Slides)

Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective cure or preventative treatment. Amyloid-beta protein (A-beta) has become a major therapeutic target in recent years due to the genetic linkage between AD and mutations in the amyloid precursor protein (APP) in a small number of families, its presence in cerebral plaques, and its neurotoxic properties. Many efforts are underway to either reduce the production of A-beta or enhance its clearance.

Keywords: Alzheimer's disease, amyloid-beta protein, immunotherapy, vaccine, B cells

Nucleic acid delivery to mammalian mitochondria - myth or reality?

Authors: M. Koulintchenko, A. Dietrich, R.N. Lightowlers
Audio: (Audio)

All nucleated cells in the body contain mitochondria and all mitochondria contain copies of their own genome, mtDNA. This small molecule is present in hundreds or thousands of copies per cell and encodes thirteen subunits of the apparatus that couples ATP synthesis to cellular respiration. Thus, mutations of this genome can have profound consequences. This area of research has gathered new momentum with the inference that mtDNA mutations can underlie neurodegenerative disease and have been implicated in the ageing process.

Keywords: mtDNA, mitochondrial transfection, mitochondrial gene expression , ,

Analysis of candidate genes in celiac disease. A tool to identify life threatening associated genes?

Authors: D. Nuzzo, F. Cataldo, L. Scola, G.I. Forte, A. Crivello, A. Giacalone, S. Accomando, G. Candore, C. Caruso, D. Lio

Given the clear role of gluten in causing autoimmunity, celiac disease (CD) represents a unique example of an immune mediated disease for which early diagnosis and dietary treatment can prevent its severe, sometimes life threatening, complications. Patients with undiagnosed and untreated CD, as well as those diagnosed later in life, have an increased morbidity and mortality due to associated conditions. Since CD is a multisystem disorder, these patients are at risk of chronic ill health, permanent stunted growth, infertility, skeletal disorders, and malignancy.

Keywords: Celiac disease, longevity, TGF-beta2, centenarians ,

Psycho-social aspects and zinc status: is there a relationship in favour of a successful ageing?

Authors: Fiorella Marcellini, Cinzia Giuli, Roberta Papa, Eugenio Mocchegiani

The ZINCAGE Project (contract no: Food-CT-2003-506850) is supported by the European Commission in the Sixth Framework Programme.. It is a large study that evaluates the effect of the zinc metabolism in order to reach healthy ageing, with a multidisciplinar approach (genetic, biochemical and social-psychological). One of the aim of the study is the evaluation of the relationship between zinc and psychosocial conditions (such as cognitive functions, mood, perceived stress value), dietary habits and lifestyle (i.e.

Keywords: , , , ,

A novel form of ALT telomere maintenance in human cells

Authors: David Cavazos [1], Richard Montellano [1], Qijun Chen [2], F. Brad Johnson [2], and Robert A. Marciniak [1,3]
Audio: (Audio)

All cancer cells must acquire a mechanism to maintain telomeres. In the majority of immortal tumors, telomeres are maintained by activation of expression of telomerase. In approximately 5-20% of tumors, telomeres are maintained by a telomerase-independent mechanism that appears to depend on recombination, termed the alternative lengthening of telomeres (ALT). ALT cells have previously been characterized by heterogeneously sized TTAGGG telomere repeats that extend beyond 50 kb in length and by the presence of novel nuclear structures, ALT-associated PML (AA-PML) bodies.

Keywords: , , , ,

Protection and Selection for Gene Therapy in the Haemopoietic System

Authors: G. Margison, L.J. Fairbairn
Audio: (Audio) (Slides)

Myelotoxicity is a frequent complicating factor in anti-cancer chemotherapy. We have been developing a gene therapy approach to addressing this, using retroviral transfer and expression of the DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT) to bone marrow stem and progenitor cells. Using a mutant version of the protein, MGMTP140K, which is resistant to clinically useful inactivators of the wild-type protein, we have shown that this provides inactivator-insensitive protection to bone marrow in vivo.

Keywords: , , , ,

The aging gut motility decay: may symbiotics be acting as biological pace-makers?

Authors: Y. Metugriachuk, F. Marotta, O. Kuroi, K. Pavasuthipaisit, J. Tsuchiya, A. Lorenzetti, E. Fesce, E. Minelli

In recent years it has been shown how dysbiosis, through several mechanisms, may affect the gut motor and sensory activity and this hold particularly relevant during the physiological age-related microflora derangement. We investigated under well-controlled and carefully characterized conditions the influence of a symbiotic formulation on the myoelectric activity of the small intestine and colon of 18-month aged male Wistar rats. Rats were fasted for 12h before the experiments which were carried out at regular timing.

Keywords: aging gut, motility, symbiotics , ,

Liver exposure to xenobiotics: the aging factor and potentials for novel nutraceuticals

Authors: F. Marotta, P. LeCroix, M. Harada, K. Masulair, P. Safran, A. Lorenzetti, S.K. Ono-Nita, P. Marandola

It has been shown that metals undergo redox cycling resulting in the production of reactive oxygen species and a number of mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Indeed, the most important mechanism of oxidative damage to proteins is metal-catalyzed oxidation which may end up in the loss of enzymatic activity and alteration of protein structure and may participate in the induction of DNA damage and oncogenesis.

Keywords: aging liver, xenobotics, YHK, nutraceutical ,

Age-Related Susceptibility Of Red Blood Cells To Oxidative Stress: A Preliminary Nutraceutical Approach

Authors: F. Marotta, P. Marandola, C. Yoshida, L. Packer

Recent studies point out the role of oxidative damage to biomembranes in a number of chronic inflammatory and degenerative diseases. In particular, despite no overt changes have been reported in erythrocytes (RBC) with advancing age, peroxinitrite anion-related damages to platelets and RBC have been implicated in age-related neurodegenerative disease.

Keywords: erythrocytes, aging, oxidative stress, nitric oxide synthase, nutraceuticals

Increase of vaccines adjuvanticity by succinylation of vaccine antigen

Authors: A.V. Martynov, E.M. Babych, M.V. Smelyanskaya

Low adjuvanticity of vaccine antigens is one of the main problems in development of antiviral and anticancer vaccines. This situation forces researches to use a number of adjuvants. When Freundt adjuvant was used with diphtherial anatoxin (as vaccine antigen) maximum titer of induced antibodies was 1:500 at injection introducton of vaccine in accordance with Pasteur scheme. We have developed technology for increasing vaccine antigen adjuvanticity by 100 times at oral use of such antigen. Technology is based on partial chemical modification of vaccine protein antigen.

Keywords: adjuvanicity, oral vaccines, succinylation, cytomegalovirus, herpes simplex virus

Genetic modification of hematopoietic stem cells: from bench to bedside....and back

Authors: F. Mavilio
Audio: (Audio)

Transplantation of genetically modified hematopoietic stem cells (HSCs) is a potential therapy for a variety of genetic and acquired blood disorders, such as severe combined immunodeficiencies (SCIDs), thalassemia and AIDS. Recent improvements in stem cell culture and vector technology are providing new tools for obtaining clinically relevant numbers of genetically modified HSCs. A number of crucial issues, however, remain unresolved, and need to be addressed for genetic modification of HSCs to enter routine clinical practice.

Keywords: gene therapy, retroviral vectors, insertional mutagenesis, genetic diseases,

Age-dependent Mitochondrial Abnormalities and Structural Changes in Rat Kidney Are Delayed by Adult-onset Calorie Restriction

Authors: S.H. McKiernan, V.C. Tuen, J.M. Aiken

Mitochondrial and structural changes were examined in aging male Fischer 344 x Brown Norway rat kidneys and the effect of adult-onset calorie restriction on those changes determined. Kidney morphology and electron transport system (ETS) enzyme activities were analyzed in frozen histological kidney sections from 18-, 24-, 30-, and 36-month old ad libitum (AL) fed rats and 24-, 30-, and 36- month 40% calorie restricted (CR) rats. Significant age-related increases in glomerulosclerosis, tubular atrophy, interstitial fibrosis, and vascular wall thickening for the AL rats were observed.

Keywords: rat, kidney, calorie restriction, mitochondria,

Gene therapy that safely targets and kills tumor cells throughout the body

Authors: D. Meruelo, J. Tseng, A. Hurtado, B. Levin, C. Pampeno

We studied the therapeutic value of Sindbis vectors for advanced metastatic cancer by using a variety of clinically accurate mouse models and have demonstrate through imaging, histologic, and molecular data that Sindbis vectors systemically and specifically infect/detect and kill metastasized tumors in vivo, leading to significant suppression of tumor growth and enhanced survival. Use of two different bioluminescent genetic markers for the IVIS Imaging System permitted demonstration of an excellent correlation between vector delivery and metastatic locations in vivo.

Keywords: Sindbis vectors , gene therapy in vivo, tumors , ,

How Evolutionary Thinking Affects our Ideas about Aging Interventions

Authors: J. Mitteldorf

If we think that aging is caused by many parts of our bodies wearing out simultaneously, then we must address these problems one-by-one. If we think that the body is programmed to turn off its protective programs, or even to self-destruct, turning apoptosis and the immune system upon its own cells, then all we need to do is to thwart these programs, mimicking or interfering with the body's signal processes as we have done in so many other areas to good effect.

Keywords: evolution, population dynamics, group selection, ,

Zinc homeostasis in aging: two elusive faces of the same metal

Authors: E. Mocchegiani, L. Costarelli, R. Giacconi, C. Cipriano, E. Muti, M. Malavolta
Audio: (Audio) (Slides)

Zinc is required for the catalytic, structural and regulatory functions of > 300 enzymes, including representatives from all six major functional classes. Moreover, zinc is also a structural cofactor for many proteins and transcription factors, including the ubiquitous zinc finger DNA binding proteins.

Keywords: zinc, zinc homeostasis, aging, metallothioneins ,

Enzymic Repair and Prevention of Chemical Aging by the Maillard reaction in Vivo

Authors: V.M. Monnier, D.R. Sell, X. Wu, D. Zhenyu
Audio: (Audio)

The Maillard Reaction is the reaction that occurs between carbonyl compounds stemming from the reaction of reducing sugars and oxidized lipids with proteins, DNA and other nucleophiles to form advanced glycation endproducts (AGEs) and crosslinks. Recent data from our laboratory has identified glucosepane, a lysyl-arginine crosslink, as the single major protein crosslink from glucose in aging human collagen.

Keywords: glycation, collagen, lens crystallins, diabetes, aging

Catechin-vanilloid synergies with potential clinical applications in cancer

Authors: D.M. Morré, D.J. Morré
Audio: (Audio) (Slides)

Demographics predict future increases in cancer burden as the global population grows and ages. These trends present challenges to develop and implement improved anticancer strategies with absolute cancer specificity and low or no toxicity to non-cancer cells and tissues. Our work has identified a cancer-specific cell surface protein, tNOX, as a target for low dose cell killing (apoptosis) of cancer cells by green tea catechin and Capsicum vanilloid combinations. This protein is unique in that it is associated with all forms of cancer and is absent from normal cells and tissues.

Keywords: tNOX, cancer target, catechin-vanilloid synergies, transgenic, green tea

Aging-related cell surface ECTO-NOX protein, arNOX, a preventive target to reduce atherogenic risk in the elderly

Authors: D.J. Morré, D.M. Morré
Audio: (Audio)

We have identified a family of constitutive cell surface ECTO-NOX proteins capable of oxidizing reduced quinones. Initially described as NADH oxidases, oxidation of external NADH was subsequently determined not to be a physiological substrate but rather a convenient method for measurement of the activity.

Keywords: aging, ECTO-NOX proteins, arNOX, atherogenic, superoxide

Refining oxidative aging theories with antioxidant enzyme knockout mice

Authors: F. Muller

The free radical theory of aging is currently one of the most popular explanations on how aging occurs at the molecular level. Our group recently published that mice partially deficient in the antioxidant enzyme manganese superoxide dismutase (Sod2+/-), have increased DNA oxidative damage (8-oxo-dG), increased tumor burden, but do not exhibit a shortened lifespan and do not exhibit acceleration of age-related biomarkers.

Keywords: , , , ,

Autophagy in Alzheimer's Disease Pathogenesis

Authors: R.A. Nixon
Audio: (Audio)

Cellular protein turnover is mediated largely by the proteasome and lysosomal system. While proteasome activity declines during aging and Alzheimers disease (AD), the lysosomal system is mobilized in vulnerable neurons early in the disease. Macroautophagy, a major pathway to lysosomes for the turnover of organelles and long-lived proteins, involves the sequestration and degradation of these cytoplasmic constituents within a series of vesicular compartments (autophagic vacuoles or AVs).

Keywords: lysosomes, proteasome, cathepsins, Alzheimer's disease, amyloid

Selective Accumulation of mtDNA Deletion Mutations in Aged Skeletal Muscle

Authors: J.W. Pak, J.M. Aiken

MtDNA deletion mutations accumulate to high levels in aged muscle fibers. This accumulation is segmental and focal; i.e., only a portion of a fiber is affected by each deletion event. Concomitant with the deletion mutations are enzyme abnormalities of the electron transport system (ETS) and intra-fiber atrophy. Quantitation of the deletion mutation abundance within ETS dysfunctional region demonstrated that greater than 90% of the mitochondrial genomes contained deletion mutations.

Keywords: Mitochondrial DNA, deletion mutations, ETS abnormality, fiber type, sarcopenia

Delivery of enzymes and neurotrophic proteins to treat CNS disorders

Authors: W. Pan, A.J. Kastin

Regeneration of the central nervous system (CNS) encounters the obstacles of inefficient delivery and degradation of neurotrophic molecules when used as therapeutic reagents. Although the blood-brain barrier (BBB) prevents free permeation of enzymes and neurotrophic proteins, it permits selective permeation of certain peptides and proteins by way of specific transport systems.

Keywords: blood-brain barrier, neurotrophic protein, cytokine, transport, neuroregeneration

Natural substances that regenerate and heal- My 20 years experience

Authors: J.G. Paraki

Health and well-being of individuals, families and community is largely dependent on the index of chronic diseases in the community. Chronic diseases drain the vitality of communities and the extent of problem often is undetected and not amenable to measurement. However hospital statistics like number of days of hospital stay, number of drugs prescribed for each patient, number of procedures performed on patients all indicate the Quality of Life of patients and hospitals. All over the world the movement is towards Wellness, Preventive and Pro-active Healthcare.

Keywords: Entropy, Decay, nature, consciousness, substances

Mitochondrial superoxide generation causes heterogeneity in replicative senescence

Authors: J.F. Passos, K. Schäuble, G. Saretzki, T. von Zglinicki

Recently, our group has shown that heterogeneity in replicative senescence is due to stochastic cell-to-cell variation in telomere length. Now, we show for the first time that "prematurely senescent" cells from a culture of young human fibroblasts have higher ROS than proliferating cells, as do fully senescent cells. Moreover, we show that mitochondrial membrane potential declines in both prematurely and fully senescent cells, and that this is a consequence of ROS dependent expression of UCP-2.

Keywords: uncoupling, telomeres, senescence, ROS, UCP-2

Does stem cell therapy for ischemic cardiomyopathy result in the improvement of congestive heart failure?

Authors: A.N. Patel

Background: Stem cell therapy has shown to improve left ventricular function in patients with ischemic cardiomyopathy. Serum B type natriuretic peptide (BNP) has been to used to evaluate the neurohormonal status of congestive heart failure symptoms. The goal of this study was to determine if serum BNP levels improved in ischemic cardiomyopathy patients under going stem cell therapy.

Methods: After IRB and government approval, adult autologous stem cell therapy was performed in patients with coronary artery disease and an ejection fraction of

Keywords: stem cell, heart failure, adult, ,

Immunorejuvenation in the elderly

Authors: G. Pawelec, S. Koch, C. Gouttefangeas, A. Wikby
Audio: (Audio)

Dysregulated T cell-mediated immunity contributes materially to the increased susceptibility to infectious disease, and possibly cancer, in the elderly. One hallmark of this state of "immunosenescence" is the predominance of large clones of peripheral T cells with limited antigen receptor heterogeneity and a corresponding contraction of diversity in the T cell antigen recognition repertoire.

Keywords: immunosenescence, immune risk profile, clonal exhaustion, T cells, Cytomegalovirus

Ageing, amyloid and amyloidosis: from pathogenesis to therapy

Authors: M.B. Pepys
Audio: (Audio)

Amyloidosis is a clinical disorder caused by extracellular deposition of insoluble abnormal fibrils, with a pathognomonic structure, derived from aggregation of misfolded, normally soluble, protein. About twenty three different unrelated proteins are known to form amyloid fibrils in vivo, each associated with clinically distinct conditions. Systemic amyloidosis, with amyloid deposits in the viscera, blood vessel walls and connective tissue, is usually fatal and is the cause of about one per thousand deaths in developed countries.

Keywords: Amyloid, Amyloidosis, Protein misfolding, Aggregation, Therapy

Encouraging support for the funding of aging research through the use of competitive prizes

Authors: K. Perrott, D. Gobel, A.D.N.J. de Grey

The most significant roadblock to increased funding for research into the causes of aging is lack of public awareness, despite discoveries that indicate the problems associated with aging may not be as intractable as previously thought. As well, aging research still suffers from association with unscrupulous purveyors in the anti-aging industry, who use unfounded product claims as a means for profit.

Keywords: funding, competition, aging, prize,

Scientific Controversy as Farce: Disciplining Homeopathic Claims

Authors: C.J. Picart

This paper argues that the resolution of the so-called "Ghostly Molecule" hypothesis-which attempted to provide scientific evidence for the claims of homeopathic principles, and have been linked to anti-aging claims in various ways-initially employed the structure of a farce. This farcical structure blurred the boundaries separating contingent (informal) and constituent (formal) forums of scientific argument; later, via a problematic rhetorical appeal to standard canons, this case was forcefully brought to a close by the editor of Nature.

Keywords: homeopathy, scientific controversy, farce, rhetoric of science, humor

Using zinc finger nucleases to manipulate the mammalian genome

Authors: M.H. Porteus
Audio: (Audio) (Slides)

Gene targeting is the replacement of an endogenous segment of DNA with an exogenous segment by homologous recombination. Through gene targeting both small and large sequence changes can be introduced into the genome and it is the most precise method of genomic manipulation. It has been a cornerstone of research in yeast and murine embryonic stem cells. Because of its precision, gene targeting could be an ideal approach to treating monogenic diseases.

Keywords: , , , ,

The Supercentenarian Research Foundation

Authors: S.R. Primmer, E. Bergman, D. Platika, L.S. Coles, A.D.N.J. de Grey, K. Ullis, D. Gobel, R.D. Young
Audio: (Audio)

The Supercentenarian Research Foundation (SRF) is being formed as an international 501(c)(3) organization to accept tax deductible donations that will be utilized to fund research into the biology of aging. The initial focus will be on supercentenarians, their siblings, and offspring, but successively younger age groups will also be investigated.

Keywords: supercentenarians, autopsies, aging, funding ,

To Engineer a Heart

Authors: B.D. Ratner
Audio: (Audio)

A University of Washington, NIH-funded, Bioengineering Research Partnership (BRP) has the challenging goal to tissue engineer (or regenerate) heart muscle that might be useful for in vivo reparative surgery. The unique muscle cells populating the heart, cardiomyocytes, have lost the ability to replicate. The heart muscle itself is highly vascularized. Muscle tissue is also aligned, organized with a mechanically appropriate extracellular matrix and innervated. Surgical considerations must be addressed.

Keywords: Tissue Engineering, Bioengineering, Heart , ,

Immune Sensing of Latent Cytomegalovirus Reactivation and its Possible Impact on Immune Senescence

Authors: M.J. Reddehase
Audio: (Audio) (Slides)

Productive cytomegalovirus (CMV) infection is resolved and fatal disease is prevented by a functional immune system, primarily by CD8 T cells, but a magic hat appears to preserve the virus from being eliminated. The viral genome persists for the lifetime of its host in the presence of a fully developed, protective antiviral immune memory. This phenomenon,- known as virus latency -, is a hallmark that CMVs share with all other members of the herpesvirus family.

Keywords: Cytomegalovirus, Latency, Memory Cells, Silencing, Reactivation

Chromatin remodeling may enforce cell senescence

Authors: K. Riabowol
Audio: (Audio) (Slides)

Normal human cells that divide in culture undergo a limited number of populations doublings commonly referred to as the Hayflick limit. Mammalian tissues that normally replicate, acquire increasing proportions of cells that cannot divide and that are in a state of replicative senescence. Mounting evidence indicates that the rate at which these populations of cells accumulate contributes to determining biological lifespan. Many stresses contribute to limiting replicative lifespan.

Keywords: senescence, ING1, chromatin, acetylation, stress

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