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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.

p53: A little more, a little less... Still screwed

Authors: G. Hinkal, C. Gatza, L.A. Donehower

The transcription factor p53 has been described as the guardian of the genome. It responds to a wide range of cellular stressors, and its response reflects the degree of said stress that a cell endures. The response ranges between activation of pathways responsible for apoptosis, cell cycle arrest, or senescence. Predictably, p53 knockout mouse models, both p53+/- and p53-/-, exhibit a dominant early death-by-tumor phenotype.

Keywords: p53, senescence, antagonistic pleiotropy , ,

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

Molecular mechanisms of telomerase regulation in genetically defined human stem cell models

Authors: Hockemeyer D.

The essential role of telomerase in stem cell maintenance has long been recognized. Nevertheless, we still have little understanding of the molecular mechanisms by which human cells regulate telomerase activity to ensure tissue homeostasis and how its dysfunction can lead to aging and tumorigenesis. The natural regulation of telomerase activity in human tissue and the impact of telomere shortening on untransformed human cells can only be studied in a primary human stem cell system.

Keywords: ZFN, TALEN, telomerase, stem cells, site-specific nuclease

Revitalization and life span extension by xenogenic fetal materials: laboratory rodent and cell culture studies

Authors: G. Hofecker, A. Strasser, H. Niedermüller, C. Gabler

Parenteral administration of xenogenic fetal materials to old rats had been shown by Kment and coworkers in the 1960ies and 1970ies to compensate for at least some age-related losses of physiological capacity in aged rats.

Keywords: revitalization, xenogenic fetal mesenchyme, Yac-1, life span ,

Global Loss of Imprinting in Embryonic Stem Cells Leads to Widespread Tumorigenesis in Adult Mice

Authors: T.M. Holm, L. Jackson-Grusby, T. Bambrick, Y. Yamada, W.M. Rideout 3rd, R. Jaenisch
Audio: (Audio)

Imprinting is a mammalian adaptation whereby subsets of genes are differentially expressed depending on their parental origin; this monoallelic expression is maintained by DNA methylation. Loss of imprinting (LOI) is a common feature of many human tumors, yet whether LOI directly promotes tumorigenesis or is merely a consequence of epigenetic deregulation in transformed cells is unclear.

Keywords: Cancer, Stem cells, Loss of Imprinting , ,

High efficiency human genome editing using designed zinc finger nucleases

Authors: F.D. Urnov, M.C. Holmes, J.C. Miller, D.E. Paschon, D.Y. Guschin, K.A. Kim, J. Wang, N.S. Wang, R.C. DeKelver, V.M. Choi, H.C. Sun, E.A. Moehle, A. Waite, E.J. Rebar, P.D. Gregory

Two distinct pathways, homology-directed repair (HDR) and non-homologous end joining (NHEJ), have evolved to eliminate double-strand breaks in eukaryotic cells. Work by Jasin et al. on the homing endonuclease I-SceI demonstrated that a DSB stimulates HDR in mammalian cells. The invention of zinc finger nucleases (ZFNs) by Chandrasegaran et al. paved the way for pioneering work by the Carroll et al. on the use of ZFNs in Xenopus and Drosophila, which was followed by studies from the Baltimore lab on ZFN-driven reporter gene targeting in human cells.

Keywords: zinc finger nuclease, genome editing, targeted integration, gene disruption ,

Naturally long-lived animal models for the study of slow aging and longevity

Authors: D.J. Holmes
Audio: (Audio) (Slides)

Arguably, the most effective 'engineer' of long life spans and anti-aging mechanisms thus far has been evolution by natural selection. Senescence theory predicts that organisms with effective protections against mortality will evolve delayed reproduction, efficient mechanisms of long-term somatic maintenance, and slow aging. A substantial body of literature supports this prediction. Vertebrate species now known to have remarkably slow or negligible rates of aging-related fitness declines in nature include certain fishes, turtles, birds, and flying, gliding or subterranean mammals.

Keywords: longevity, evolution, reptiles, fishes, turtles

Which ages first--the chicken or the egg? A comparative test of the ovarian depletion hypothesis of female reproductive aging

Authors: D.J. Holmes, M.A. Ottinger, S.L. Thomson, J.M. Wu

Conventional wisdom holds that depletion of finite oocyte stores is the prime mover in reproductive aging in female birds and mammals. This idea remains pervasive, despite 1. published evidence that some laboratory rat strains reach infertility with a considerable pool of eggs still in reserve; and 2. little rigorous comparative testing. Ovarian declines may be secondary in some species to decaying function of the hypothalamic-pituitary-ovarian (HPO) axis or other factors.

Keywords: ovarian aging, infertility, birds, oocytes, hypothalamic-pituitary-ovarian axix

Allotopic expression: mitochondrial to nuclear gene transfer

Authors: I.J. Holt, M. Bokori-Brown, M. Hamalainen

Mitochondria contain their own genome, whose 13 protein products are essential for life. Life-long deterioration of mitochondrial DNA has been proposed to be a significant factor in the normal ageing process. In principle, transfer of the 13 mitochondrial genes to the nucleus would obviate the need to maintain a separate genome in the mitochondrion, and so could enhance longevity. Gene transfer from mitochondrial DNA to the nucleus has happened innumerable times during the course of evolution and so there does not appear to be an insuperable barrier to the process.

Keywords: , , , ,

The value of life to persons as conative processes

Authors: S. Horrobin

Any project to extend human or more particularly personal life span requires some fundamental rationale which underpins and motivates it. An understanding of the origin and nature of the motivations towards life extension for persons, arising from an analysis of the fundamental structure of personhood, is therefore warranted. This paper offers an analysis of the origin, nature and structure of the process of personhood by which this motivation may be understood, and upon which may be established the value of, and so the rationale for the project of life extension.

Keywords: ethics, value, nature, conatus, life extension

Designing enzymes ab initio

Authors: K.N. Houk, G. Kiss, F. Schoenebeck, S.A. Johnson, S. Kim, G. Nosrati

The computational design of enzymes for new reactions, and the expression of these designed proteins and measurement of catalytic activity have been carried out in collaboration with David Baker at the University of Washington and Stephen Mayo at Caltech. This protocol holds promise for the production of new therapeutic enzymes. Catalytic sites are designed through quantum mechanical calculations, and these theoretical catalytic sites ("theozymes") are incorporated into stable protein scaffolds with the Rosetta programs of Baker et al.

Keywords: catalysis, protein, quantum mechanics, molecular dynamics,

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

Polysaccharides from medicinal herbs as potential therapeutics for ageing and age-related neurodegeneration

Authors: Li HF, Hu MH, Ma FL, Xiao LY, Zhang J, Xiang YX, Huang ZB

 

Polysaccharides from medicinal herbs as potential therapeutics for ageing and age-related neurodegeneration

 

Haifeng Li1,2, Minghua Hu1, Fangli Ma1, Lingyun Xiao2, Ju Zhang2, Yanxia Xiang2 and Zebo Huang2,3

 

1 Research & Development Centre, Infinitus (China) Company Ltd, Guangzhou 510665, China

2 School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China

Detection of Parkinson's Disease associated α-synuclein fibrils by fluorescence microscopy

Authors: S. Huebinger, O. Bannach, A. Funke, D. Willbold, E. Birkmann

Introduction: Parkinson's Disease (PD) is one of the most common neurodegenerative diseases in humans, and the most common one associated with motor deficiencies [1]. It mainly affects the elderly with a peak age of onset at around 60 years [2], although familiar forms are known that show an earlier onset of disease. The symptoms are caused by the degeneration of dopaminergic neurons in the brain, which are accompanied by the misfolding and aggregation of the protein α-synuclein.

Keywords: Parkinson, Synuclein, Detection, Fluorescence Microscopy, Diagnosis

The function of POT1 in the ALT pathway in cancer cells

Authors: Hunt T, Halvorsen D, Silva H

All cells, including cancers, have telomeres which gradually shorten as the cell divides1. Once the telomeres are too short, the cell senesces. Cancer cells divide uncontrollably and thus require telomere maintenance mechanism (TMM) to prevent telomere shortening and avoid senescence. There are two types of TMMs, the first is telomerase-based, wherein this specific polymerase gradually extends telomere ends. There are several anti-telomerase treatments that are in clinical trials2. The second TMM is known as alternative lengthening of telomeres (ALT).

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: , , , ,

Reprogramming Somatic Cells to Pluripotency Using Small Molecules

Authors: J. Ichida

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

Keywords: , , , ,

Protective effect of a sturgeon egg homogenate marine compound but not of EPA/DHA on arterial ultrastructure in spontaneously hypertensive rats

Authors: Bertuccelli G, Marotta F, Illuzzi N, Nagpal R, Zerbinati N, Naito Y, Mohania D, Milazzo M, Sapienza C, Italia A, Tomella C, Catanzaro R.

It has been reported that with hypertension there is an increase in lipid peroxidation products of erythrocytic membranes of humans and of aortas of spontaneously hypertensive rats (SHR). Indeed, SHR are considered to be a genetic model of hypertension mimicking idiopathic hypertension in humans.

Keywords: sturgeon egg preparation, arterial ultrastructure, EPA/DHA, Caviarlieri

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,

Development of calorie restriction mimetics as a prolongevity strategy

Authors: D.K. Ingram
Audio: (Audio)

By applying calorie restriction (CR) at 30-50% below ad libitum levels, studies in numerous species have reported increased lifespan, reduced incidence of age-related diseases, improved stress resistance, and decelerated functional decline. Whether this nutritional intervention is relevant to human aging remains to be determined; however, evidence emerging from CR studies in nonhuman primates suggests that response to CR in primates parallels that observed in rodents. To evaluate CR effects in humans, clinical trials have been initiated.

Keywords: nutrition, insulin, glucose, metformin, dopamine

Monkeying around with calorie restriction: is a calorie a calorie?

Authors: Ingram DK, Roth GS, de Cabo R, Mattison JA.

Dietary caloric restriction (CR) is the only intervention repeatedly demonstrated to retard the onset and incidence of age-related diseases, maintain function, and extend both lifespan and healthspan in mammals. In 70 years of study, such beneficial effects have been demonstrated in rodents and lower animals, but prior to 1987, had never been examined in primates. To determine whether CR might eventually be applied to humans, the NIA initiated a study of CR and aging in nonhuman primates.

Keywords: calorie restriction, primate, aging, NIA

Epigenetic therapy

Authors: J.P. Issa
Audio: (Audio) (Slides)

Neoplastic cells have numerous clonal changes in gene expression when compared to normal cells. Some of these differences in gene expression are permanent, unrelated to structural alterations in DNA, and have been referred to as epigenetic changes. One of the common mediators of epigenetic changes in human cells is a biochemical process termed DNA methylation that adds a methyl group to the cytosine base.

Keywords: epigenetic, methylation, aging, cancer ,

Approach to Assessing the Walking Motion of Elderly Males Based on Kinetic Parameters of Young Males

Authors: F. Ito,T. Mori,K. Kikkawa, H. Okada

This study seeks to propose a method to assess the walking motion of elderly males using criterial kinetic parameters for young males during walking and to suggest how to maintain their walking capabilities at the same level as those of young males. For this purpose, we used the coefficient of variation (= SD / MEAN * 100, CV), z-score and weighted z-score (= z-score /CV) to clarify parameters that differentiate the walking of elderly males from that of young males. The subjects were 13 healthy young Japanese males and 104 healthy elderly Japanese males.

Keywords: motion analysis, gait, aging assessment, inverse dynamics,

Herpes simplex virus type 1 in brain is a cause of the neuropathological features of Alzheimer's disease

Authors: R.F. Itzhaki, M.A. Wozniak

The causes of Alzheimer's disease (AD) have still to be elucidated, despite the huge number of studies on the main neuropathological features of the disease - amyloid plaques and neurofibrillary tangles. Our research has implicated the common virus, herpes simplex virus type 1 (HSV1), as a major factor in the condition when it is present in brain of people carrying the type 4 allele of the apolipoprotein E gene (APOE) (Jamieson et al., 1991, 1992; Itzhaki et al., 1997; Lin et al., 1998; Wozniak et al., 2005).

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

Antiviral agents inhibit Alzheimer's disease-like changes in herpes simplex virus-infected cells in culture

Authors: R.F. Itzhaki, A.L. Frost, M.A. Wozniak

The causes of Alzheimer's disease (AD) in non-familial cases, which comprise the vast majority, are unknown. We have implicated herpes simplex virus type 1 (HSV1) as a major factor, on discovering that it resides latently in many elderly brains (J. Med. Virol., 1991, et seq.), that in carriers of the type 4 allele of the apolipoprotein E gene (APOE-ε4) it confers a strong risk of AD (Lancet, 1997), and that it reactivates in brain, possibly recurrently (J. Med. Virol., 2005).

Keywords: Alzheimer's disease, herpes simplex virus type 1, antivirals, amyloid, tau

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

The role of viruses and of APOE in dementia

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

Herpes simplex virus type 1 (HSV1) has been implicated in Alzheimers disease (AD) because of its ubiquity, its propensity for neuronal latency and because in herpes simplex encephalitis (HSE), it affects the same brain regions as those mainly damaged in AD. We established, using PCR, that HSV1 DNA is present in brain of most elderly people, including AD patients. Subsequently we found that in carriers of the type 4 allele of the gene for apolipoprotein E (APOE), the virus is a major risk factor for AD [1,2].

Keywords: Alzheimer's disease, herpes simplex virus, APOE, intrathecal antibodies, amyloid precursor protein

Characterization of decellularized thymus scaffolds for use in engineering thymus tissue

Authors: Jackson JD, Ryu SW, Kim N, Busse K, Ju YM, Albanna M, Soker S, Yoo JJ

The thymus is a primary lymphoid organ that is responsible for the maturation of T lymphocytes.  During aging, the thymus undergoes a process of involution.  This results in a decrease in T cell output from the thymus as well as a change in the distribution of T cells in the periphery.  To overcome these problems of aging, we are developing an engineered thymus that may provide a method to increase the number of naive mature T cells and to enhance immune responses to pathogens.

Keywords: thymus, tissue engineering, scaffold

Free and Open Science and Technology

Authors: Jackson JP III.

There is a growing consensus that the costs of intellectual property rights threaten to undermine the very progress these rights are intended to promote. Particularly in biotechnology, where innovation depends on integrating complex chains of components, royalty stacking and "patent thickets" surrounding key technologies can cause an entire field to stagnate (eg the WARF patents). In the past 30 years, the life sciences have failed to deliver on their promise, with only a few "lottery winners" such as Amgen and Genetech, amidst a sea of "losers" that never turn a profit.

Keywords: Open Source Biotechnology, Patents

Thymic Tissue Regeneration Using Natural Scaffolds

Authors: J.D. Jackson, B. Lee, S. Soker, A. de Grey, A. Atala, J.J. Yoo
Video: (Video)

Tissue engineering offers the potential for treatment of many age related diseases. Decreased immunity is a major problem in the elderly resulting in the increase of infection related problems along with a decreased effectiveness of vaccination. T cells develop and mature in the thymus. During aging, the thymus undergoes involution resulting in a decrease in T cell production. Methods to increase T cell output from the thymus have the potential to improve the immune function of older individuals.

Keywords: thymus, tissue engineering, T cell, scaffold, immunity

Extension of Drosophila Lifespan by Rhodiola rosea Through an Anti-oxidant Independent Mechanism

Authors: Schriner SE, Abrahamyan A, Holmbeck M, Pavlov Jr A, Bussel IE, Jafari M.

Rhodiola rosea is an adaptogenic plant that can increase the resistance of an organism to physical, mental and environmental stresses. Previously, we found that R. rosea could extend the mean life span of the fruit fly, Drosophila melanogaster, approximately 7%. We evaluated a new formulation of R. rosea (SHR-5) which contains elevated levels of the putative active compounds (rosin, rosarin, and rosavin), and found that it could extend mean life span by 43% (P<0.0001), and maximum life span by 33% when compared to control diet fed flies. The precise mechanism of R.

Keywords: Rhodiola rosea, Drosophila, Lifespan, Anti-oxidants, Oxidative stress

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

Immunopharmacotherapy against weight gain

Authors: K.D. Janda, E.P. Zorrilla

About 1 billion people worldwide are overweight or obese (body mass index=25-30 or >30 kg/m2, respectively), with disproportionately higher prevalence rates in affluent countries. For example, in the United States, the National Health and Nutrition Examination Survey (NHANES) found that, in 2003-2004, approximately 66% of all American adults 20 years of age or older were overweight or obese. Almost 4 out of every 5 adult men aged 40-59 were so classified.

Keywords: ghrelin, obesity, body weight regulation, vaccine, immunopharmacotherapy

Respiration, coupling and ROS in senescent human fibroblasts

Authors: E. Huetter, K. Renner, E. Gnaiger, G. Pfister, P. Jansen-Duerr
Audio: (Audio)

Human cells in primary culture have a finite lifespan, a phenomenon termed "replicative senescence". After about 50 population doublings, cells stop proliferation and arrest irreversibly in the G1 phase of the cell cycle. Cellular energy metabolism is an important aspect of aging, as shown by life span extension through caloric restriction. Analysis of the glycolytic pathway in young and old cells revealed age-associated changes in the activity of several enzymes.

Keywords: , , , ,

Biospray techniques for engineering organotypic tissues

Authors: S.N. Jayasinghe

There are several approaches for developing organotypic tissues. These range of the non-jetting to the jetting methodologies. The non-jetting approaches could simply be exemplified by the manual mixing of a matrix with a given composition of cells.

Keywords: Biosprays, Viability, Mouse models, Engineering fucntional synthetic tissues, Regenerative biology and medicine

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

Aging, Exercise and Photochemicals: Promises and Pitfalls

Authors: L.L. Ji
Audio: (Audio) (Slides)

Reactive oxygen species (ROS) generation has an important implication in the etiology of many diseases and in aging. Furthermore, strenuous physical exercise has been shown to increase oxidative stress to skeletal muscle and myocardium due to increased ROS generation. In order to optimize exercise benefits in the elderly whereas to prevent oxidative damage, we seek novel antioxidant protection, via dietary supplementation of phytochemicals in vegetables, fruits, grains, herbs and other natural sources.

Keywords: antioxidant, aging, exercise, oxidative damage, phytochemical

Aging-related changes to stem cells and the stem cell niche

Authors: Boyle M, Wong C, Voog J, Rocha M, Jones DL.

Tissue stem cells reside in specialized microenvironments, or niches, that strongly influence stem cell behavior to maintain the appropriate balance of stem and progenitor cells available for tissue homeostasis and repair. The germline stem cell (GSC) niche in the Drosophila male gonad is located at the apical tip of the testis where stem cells are in contact with the hub, a cluster of approximately 10-15 somatic cells that secrete the key self-renewal factor unpaired (upd).

Keywords: Stem cells, Niche, Germ line, Drosophila

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

Fruit polyphenols in brain aging: Effects on Signaling, Neurogenesis and Behavior

Authors: J.A. Joseph, G. Casadesus, D. Ingram, B. Shukitt-Hale
Audio: (Audio)

It is becoming increasing clear that while the research involving the molecular biology of and the determination of the genetic mechanisms of aging involves elegant science associated with state of the art techniques, it is clear that practical information on how to forestall or reverse the deleterious effects of aging may be years away. If this is the case, then it becomes prudent to try to establish other methods that may be utilized today to alter the course of aging.

Keywords: polyphenolics, brain, behavior, signaling, neurogenesis

Quenching the "Fires" of Inflammatory and Oxidative Stress: Implications for Healthy Brain Aging

Authors: J. Joseph, B. Shukitt-Hale, D. Fisher, L. Willis

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

Keywords: Inflammation, Oxidative stress, Brain aging, ,

Telomere dysfunction and stem cell aging

Authors: Ju Z.

Current evidence suggest that the functional decline of adult stem cells contributes to the impaired organ homeostasis and functionality during aging. The mechanisms of stem cell aging are still poorly understood. Telomere dysfunction represent one of the molecular mechanisms limiting adult stem cell function by triggering both cell intrinsic checkpoints and cell extrinsic alterations. Deletion of DNA damage checkpoints induced by telomere dysfunction can rejuvenate the aging stem cells and improve organ function in 3rd generation telomerase knockout mice (G3Terc-/-).

Keywords: telomere, aging, stem cell

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 ,

Is there any beneficial effect of S. boulardi lysates on NK cell activity in otherwise healthy but immunocompromised elderly subjects?

Authors: Kantah MK, Takadanohara H, Marotta F, Illuzzi N, Naito Y, Celep G, Milazzo M, Sapienza C, Tomella C, Kobayashi R, Catanzaro R.

The aim of the present study was to test the effect of KC-1317, a symbiotic mixture containing microbial lysate (Saccharomyces boulardii lysate in a cranberry, colostrum-derived lactoferrin, fragaria and lactose mixture,  Named, Italy) in healthy subjects with decreased NK activity.

Keywords: Saccharomyces boulardii lysate , NK cell activity , KC-11317

Differentiation of iPS cells into NK cells to combat cancer and HIV

Authors: D. S. Kaufman

Rejuvenation of the immune system through induced pluripotent stem cell (iPSC) technology provides a fundamentally new approach to treat and cure malignancies and chronic viral infections. iPSCs have now been made by hundreds of labs using diverse starting cell populations and reprogramming methods. Our group has used both iPSCs and human embryonic stem cells (hESCs) as starting cell populations to produce natural killer (NK) cells, key components of the innate immune system.

Keywords: induced pluripotent stem cells, human embryonic stem cells, natural killer cells, immunotherapy,

A novel technique of flow measurement using thermistor with real time graphical display for anaesthesia ventilator

Authors: Kaur J, Kumar J, Kapur P, Sohi BS.

Anaesthesia ventilator is a life saving device that is quite useful in clinical applications under general anaesthesia giving respiratory support during various surgeries in the operation theatres. When respiration takes place, flow at different points of the respiratory tract changes.

Keywords: Anaesthesia ventilator, Flowmeter, Gas flow rate, Mass flow controller, Thermistor

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: , , , ,

Mechanism of telomere shortening by oxidative stress

Authors: S. Kawanishi, S. Oikawa

In humans, shortening of telomere which contains highly conserved repeats of a characteristic hexameric sequence (5'-TTAGGG-3') is believed to be associated with cell senescence. Recently, Zglinicki et al. reported an increase of the rate of telomere shortening by oxidative stress in human fibroblasts [1]. However, the mechanism for the increase of telomere shortening rate by oxidative stress remains to be clarified. We investigated whether UVA, which contributes to photoaging, accelerates the telomere shortening in human cultured cells.

Keywords: telomere, oxidative stress, DNA damage, H2O2, UVA

Telomeres and Reproductive Aging

Authors: D.L. Keefe, L. Liu

Infertility, miscarriage and aneuploid offspring increase with age in women, and meiotic dysfunction underlies reproductive aging. How aging disrupts meiotic function in women remains unclear, but as women increasingly delay attempts at childbearing, solving this problem becomes an urgent priority. Telomeres, which consist of a (TTAGGG)n repeated sequence and associated proteins at chromosome ends, mediate aging in mitotic cells, and also may mediate the effects of aging on meiosis. Telomeres shorten both during DNA replication and from the response to oxidative DNA damage.

Keywords: telomeres, aging, meiosis, reproduction, recombination

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