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.

Observation of Preventive and Therapeutic Effects of Antithrombin-Ⅲ on Experimental Disseminated Intravascular Coagulation

Authors: H. Dong, S. Zhang, L. Li

Objective: To observe the preventive and therapeutic effects of antithrombin-III (AT-III) on experimental disseminated intravascular coagulation (DIC) in rabbits. Methods: Rabbits were at random divided into the control and AT-III plus lipopolysaccharide (LPS) or AT-III plus thromboplastin (Tp) groups. Experimental DIC was induced by injection of LPS or Tp. AT-III was intravenously injected after the injection of LPS or Tp. 2.5 hours later, blood sample were drawn and the concentration of fibrinogen, prothrombin time (PT), 3P test, platelet count, AST and CK was measured.

Keywords: Antithrombin-III, Lipopolysaccharide, Disseminated intravascular coagulation, Throm-boplastin, Rabbit

T cell replicative senescence: pleiotropic effects on human aging

Authors: R.B. Effros
Audio: (Audio) (Slides)

Elderly persons have been exposed to a myriad of pathogens over their lifespan. This life-long immunological history leads, in many cases, to the generation of expanded populations of memory T cells that have reached the end stage of replicative senescence.

Keywords: T cells, immune system, telomerase, replicative senescence ,

Telomere-initiated cellular senescence is a DNA damage checkpoint-mediated response

Authors: F. d'Adda di Fagagna, P.M. Reaper, L. Clay-Farrace, T. von Zglinicki, G. Saretzki, S.P. Jackson
Audio: (Audio)

Telomere-initiated cellular senescence is triggered when telomeres, the ends of linear chromosomes, cannot fulfil their normal protective functions. Although changes in several cellular markers have been shown to be associated with senescence, the mechanisms that control it are largely unknown. In order to gain a better molecular understanding of this phenomenon, we studied the molecular markers associated with senescence in primary human MRC5 and BJ fibroblasts. Since their life span can be extended by the expression of telomerase, senescence is telomere-initiated in these cells.

Keywords: Telomeres, senescence, DNA damage, checkpoints, human fibroblasts

Camptothecin sensitivity in Werner's syndrome fibroblasts as assessed by the COMET technique

Authors: J. Lowe, A. Sheerin, K. Jennert-Burston, J. Bird, M.H.L. Green, R.G.A. Faragher
Audio: (Audio)

Werner's syndrome (WS) is an inherited genetic disease in which individuals display the premature ageing of a selected subset of tissues. The disorder results from loss of function mutations in the wrn gene. Wrn codes for a member of the RecQ helicase family with a unique nuclease domain. There is significant evidence that the role of wrn is to assist in the repair and reinitiation of DNA replication forks that have stalled.

Keywords: Werner's syndrome, drug sensitivity, COMET assay , ,

Chronic aluminum administration to old rats results in increased levels of brain metal ions and enlarged hippocampal mossy fibres

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

The effect of chronic aluminium intake has been investigated in the central nervous system of aged male Wistar rats to assess the potential role of the accumulation of this metal ion on the development of neurodegenerative features observed Alzheimer's disease. Aluminum dichloride hexahydrate (2g/L) was administered for 6 months in the drinking water.

Keywords: Aluminum administration, brain metal ions, hippocampus, Timm's reaction, Alzheimer's disease

Senescence Marker Protein-30 (SMP30) as a novel anti-ageing molecule

Authors: D. Feng, Y. Kondo, A. Ishigami, M. Kuramoto, T. Machida, N. Maruyama

The expression of SMP30 having multifunctions is decreased with ageing in almost all organs. The amino acid sequence of SMP30 is highly conserved among various species. Intracellular localization of SMP30 is both in cytoplasm and nucleus. Since a part of SMP30 is phosphorylated , we determined phosphorylation sites by proteomic analysis. In addition SMP30 catabolizes organophosphates in the presence of cationic ions except calcium ion. Although SMP30 has been thought to be a calcium-binding protein, our study showed no eveidence on its binding to calcium ion.

Keywords: SMP30, phosphorylation, organophosphatase , ,

Motor and cognitive recovery induced by bone marrow stem cells grafted to striatum and hippocampus of impaired aged rats: functional and therapeutical considerations

Authors: C.I. Fernandez, E. Alberti, Y. Mendoza, J. Collazo, L. Martinez, J.C. Rosillo

Impairments in motor coordination and cognition in normal and pathological aging are often accompanied by structural changes i.e. loss of synapses and neurons. Also, it has been recently shown that bone marrow stem cells can give origin to cells of different tissues, including neural cells. Given the therapeutic implications of increasing health and functional possibilities in the aged brain, we have tested the effects of rat femur bone marrow stem cells, rBMSCs, grafting to the striatum hippocampus of aged rats with motor or cognitive deficits respectively.

Keywords: stem cells, aging, neural grafting, sensorimotor function, cognition

Environmental enrichment-behavior-oxidative stress interactions in the aged rat: issues for therapeutical approach in human aging

Authors: C.I. Fernandez, J. Collazo, Y. Bauza, O. Lopez

The effects of environment enrichment on motor activity, exploration and cognitive performances were studied in aged rats. Both, non-impaired (NI) and impaired (I) rats were submitted to daily training in complex-enriched environment (cEE) for 60 days. Animal were examined at spatial water maze task, passive avoidance test, open field test and sensorimotor coordination tasks (bridges test and Marshall scales). At the end of experiment animal were sacrificed for brain biochemical determinations (gluthatione content and specific-ChAT activity).

Keywords: aging, environmental enrichment, cognition, motor function, neurorehabilitation

Evidence and identification of preferential protein targets for age-related modifications in peripheral blood lymphocytes

Authors: S. Poggioli, J. Mary, H. Bakala, B. Friguet
Audio: (Audio)

Oxidatively modified proteins have been analyzed in aging human peripheral blood lymphocytes since protein modification by oxidation and other related pathways are believed to contribute to the intracellular age-related accumulation of damaged proteins, a process that has been associated with the cellular functional deficits that occur with age.

Keywords: protein modification, oxidation, lymphocytes, proteomics, mass spectrometry

2003 Flow chart of biochemical and physiological interactions in human aging

Authors: J.D. Furber

The many observable signs and symptoms of human senescence have been hypothesized by various researchers to result from several primary causes. Close inspection of the biochemical and physiological pathways associated with each of the hypothesized causes reveals several parallel cascades of events with multiple interactions and feedback loops among them.

As an aid to keeping track of the many processes and interactions, a flow chart is presented. Promising intervention points for the development of new therapeutics are also highlighted on the flow chart.

Keywords: aging, biochemistry, physiology, interactions, network

In vivo demonstration of anti-senescence effect of natural hydrophilic antioxidant carnosine

Authors: S. Gallant, A. Boldyrev

Carnosine (b-alanyl-L-histidine) is known to be a natural neuropeptide with a variety of protecting properties preventing neuronal cell death under conditions of oxidative stress. Its antioxidant (Severin et al, 1984; Aruoma et al, 1989; Boldyrev et al, 1999), immunomodulating and wound healing (Nagai and Suda, 1989) as well as radioprotective and anti-ischemic (Boldyrev and Severin, 1990; Gallant et al, 2000; Stvolinsky et al, 2002) abilities could be useful tool to prevent accumulation of senescence features (Hipkiss, 1998).

Keywords: carnosine, oxidative stress, life-span , ,

Oxidative stress and TGF-beta1: triggers of premature senescence in adult human prostate fibroblasts?

Authors: R. Gander, G. Untergasser, H. Rumpold, E. Plas, L. Tadic, P. Berger

Previous reports emphasize that oxidative stress-induced premature senescence (SIPS) of human diploid fibroblasts (HDFs) is mainly triggered by transforming growth factor beta 1 (TGF-b1). In the human prostate TGF-b1 mediates the differentiation of fibroblasts to myofibroblasts within a gradual process leading to a reactive stroma that favours epithelial cell tumorigenesis.

Keywords: cellular senescence, oxidative stress, TGF-beta, prostate fibroblasts ,

Early-Life Programming of Aging and Longevity: The Idea of High Initial Damage Load (the HIDL Hypothesis)

Authors: L.A. Gavrilov, N.S. Gavrilova
Audio: (Audio)

In 1991 we suggested a scientific idea that living organisms are developing with an exceptionally high load of initial damage, which is comparable with the amount of subsequent aging-related deterioration accumulating during the rest of entire adult life (Gavrilov and Gavrilova, 1991, "The Biology of Life Span"; http://www.longevity-science.org/index.html#Book).

Keywords: Aging Theory, Early-Life Programming, Parental Age, Season of Birth, Lifespan Inheritance

Reliability-Engineering Approach to the Problem of Biological Aging

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

25 years ago we first applied the reliability theory to explain aging of biological species (Gavrilov, 1978, PMID: 624242; Gavrilov et al., 1978, PMID: 716614). Since that time we continued the development of this theory (Gavrilov and Gavrilova, 2001, Journal of Theoretical Biology 213(4): 527-545, http://www.longevity-science.org/JTB-01.pdf) and came to the following conclusions:

Keywords: Reliability Theory, Aging Theory, Redundancy, Compensation Law of Mortality, Mortality Deceleration

Does Exceptional Human Longevity Come With High Cost of Infertility? Testing the Evolutionary Theories of Aging

Authors: N.S. Gavrilova, L.A. Gavrilov, V.G. Semyonova, G.N. Evdokushkina

The purpose of this study is to test the prediction of evolutionary theory of aging that human longevity comes with the cost of impaired reproductive success (higher infertility rates, see Nature, 1998, 396: 743-746). Our validation study is based on the analysis of particularly reliable genealogical records for European aristocratic families. This dataset is appealing to use for two reasons: (1) it has high data accuracy and completeness; (2) confounding effects of socio-economic status are minimized in this socially elite group.

Keywords: Longevity, Infertility, Reproductive Cost, Evolutionary Theories of Aging, Reproductive Success

The Methuselah Mouse Prize

Authors: D. Gobel
Audio: (Audio) (Slides)

On June 8th, 2003, the inaugural Methuselah Prize was awarded to Dr. Andrzej Bartke for the "Methuselah Mouse" that lived the equivalent of 180 human years. The Methuselah Foundation is offering prizes for specific achievements in the spirit of the Longitude Prize of 1714 for advancements in the healthy lifespan of both newborn and aged mice. The series of prizes will grow to include even more ambitious life extension competitions as progress is achieved.

Keywords: life extension, prizes, mouse models , ,

Age-related muscle loss and progressive dysfunction in mechano sensitive growth factor signalling

Authors: G. Goldspink
Audio: (Audio)

Loss of muscle mass and function (sarcopenia) is one of the most marked problems associated with ageing as it has major health care as well as socioeconomic implications. The growth hormone/IGF I axis is regarded as an important regulator of muscle mass. However, it is now appreciated that other tissues in addition to the liver express IGF-I. Also there are local as well as systemic forms of IGF-I which have different functions. We cloned two different IGF-Is that are expressed by skeletal muscle and both are derived from the IGF-I gene by alternative splicing.

Keywords: Sarcopenia, muscle mass, MGF, IGF-I, Exercise

Age related endocrine disfunctions in non-human primates

Authors: N.D. Goncharova, B.A. Lapin

Endocrine system takes part in the organization of the processes and functions that are affected by aging in the first turn: complex forms of behavior, nonspecific adaptation to stress factors of environment, reproduction, homeostasis, immune states, higher nervous activity, etc. This is why it may be suggested that age endocrine disturbanses are important factors of the processes of physiological aging and age pathology.

Keywords: Aging, adrenals, testes, pineal gland ,

Longevity and survival factors implicated in human ageing and longevity

Authors: E.S. Gonos
Audio: (Audio)

We have developed conditionally immortalized cell lines and we have cloned several senescence associated genes. Analysis of the function of one of the isolated genes (ApoJ), suggests that it is a novel survival factor. ApoJ is found over-expressed in vitro under a variety of stress conditions and in vivo in patients suffering from various age-related diseases. Stable over-expression of ApoJ inhibits apoptosis and its inhibition by RNA interference sensitizes cells to cytotoxicity.

Keywords: human, longevity, proteasome, senescence, survival

Carbon-based pharmaceuticals as a novel prolongevity strategy

Authors: E.N. Gorban, V.K. Koltover

The aim of this study was to demonstrate the prospects of applications of the novel carbon-based pharmaceuticals, namely - enterosorbents and fullerenes in biomedical gerontology. We present the results of our own studies as well as the analytical review of the literature data that were available up to now. The dietary enterosorbent, SKN non-coated nitrogen-containing carbon, was found to increase the mean value of male Wistar rats' life-span by 43%, that is comparable with the life-span prolongation effects of the calorie-restricted diets (Frolkis et al., 1989).

Keywords: aging, life-span prolongation, fullerenes, eneterosorbents ,

Regular exercise: A possible anti-oxidative strategy in ageing

Authors: S. Goto, Z. Radak, H.Y. Chung, H. Naito, R. Takahashi, H. Nakamoto
Audio: (Audio)

Moderate regular exercise is thought to be good for health, to help to retard aging and reduce incidence of age-related diseases in aged animals and elderly people. Mechanisms of these beneficial influences are not fully understood. We have investigated effects of regular exercise on oxidative modifications of proteins and DNA, and proteasome activities that can degrade oxidatively modified proteins as well as oxidative status and NF-kB in aging rat tissues.

Keywords: regular exercise, oxidative stress, adaptation, proteasome, NF-kB

Protective effects of mutant ubiquitin in transgenic mice

Authors: D.A. Gray, M. Tsirigotis, J. Brun, M. Tang, M. Zhang, M. Beyers, J. Woulfe

The ubiquitin/proteasome pathway (UPP) is responsible for elimination of damaged and misfolded proteins. In yeast it has been established that mutant isoforms of ubiquitin unable to participate in ubiquitin chain assembly exert a dominant negative effect on proteolysis (in the case of a K48R substitution) or on DNA repair (in the case of a K63R substitution). To explore the consequences of analogous mutations in the context of mammalian cells in vivo, we have created transgenic mouse strains in which wild type or mutant ubiquitin is expressed at high levels in most tissues.

Keywords: ubiquitin, proteasome , transgenic , neurodegeneration ,

The effect of environmental versus genetic influences on immunosenescence

Authors: B. Grubeck-Loebenstein
Audio: (Audio)

CD8+ CD28- T cell clonal expansions frequently occur in elderly persons who fail to produce specific antibodies following immunization. These clones express effector cell markers and are mostly CD45RA+. When isolated and put into culture they are unable to proliferate, but produce IFNgamma upon stimulation. Many of the clones specifically recognize cytomegalovirus (CMV). These CD8+ type 1 effector cells seem to trigger a Th1 polarization, as CD4+ T cells from elderly persons without in vivo antibody production produce Th1, but only low amounts of Th2 cytokines upon stimulation with PHA.

Keywords: immunosenescence, CMV, genetics, T cells ,

Rockfish: Long-Lived Animals with "Negligible Senescence"

Authors: J.C. Guerin

Field observations have suggested for quite some time that certain fish, turtles and invertebrates have extremely long maximum lifespan potential. Age validation techniques have since confirmed these observations. Negligible senescence is defined in part as no observable age-related increase in mortality rate or decrease in reproduction rate after maturity, and no observable age-related decline in physiological capacity or disease resistance.

Keywords: , , , ,

Telomerase and Regenerative Medicine

Authors: C.B. Harley
Audio: (Audio)

There is now abundant experimental evidence in multiple human cell types in culture for the causal relationships between telomere loss and replicative senescence on one hand, and telomerase activation and cellular immortalization on the other. These relationships are supported by correlative data in human aging, chronic diseases, cancer, experiments in telomerase knock-out mice, and human genetic conditions of telomerase insufficiency.

Keywords: telomerase, cancer, degenerative disease, telomere ,

What Do Hormones Have to Do with Aging? What Does Aging Have to Do with Hormones?

Authors: S.M. Harman
Audio: (Audio) (Slides)

Aging changes in body composition and metabolism bear a striking resemblance to those seen in states of male and female sex hormone, thyroid, and growth hormone (GH) deficiencies and cortisol excess. This resemblance, plus observed decreases with age in testosterone in men, estrogen in women, and GH in both sexes have led some to conclude that aging is caused by hormonal alterations and to the use of hormone replacement as anti-aging therapy.

Keywords: hormones, membrane fluidity, signal transduction , ,

Immortal Ethics

Authors: J. Harris
Audio: (Audio)

This paper outlines the ethical issues involved in life extending therapies. The arguments against life extension are examined and found wanting. The consequences of life extension are explored and found challenging but not sufficiently daunting to warrant regulation or control. In short there is no doubt that immortality would be a mixed blessing, but we should be slow to reject cures for terrible diseases which may be an inextricable part of life extending procedures even if the price we have to pay for those cures is increasing life expectancy and even creating immortals.

Keywords: Immortality, Justice, ethics, ,

Regenerative Medicine: Systematic Application of Biotechnology, Bioengineering, Nanotechnology and Information Sciences for the Improvement of Human Health

Authors: W. Haseltine
Audio: (Audio)

The human body is a self-assembling machine, comprised of trillions of tiny parts, that maintains itself in good working order for decades. Damage by disease, injury by trauma and wear by time degrades our body's function.

Keywords: , , , ,

Regulation of telomerase activity throughout life: rescue effect or cancer

Authors: M.F. Haussmann, C.M. Vleck

The evolution of senescence is thought to follow from the progressive decline in the force of natural selection after the onset of reproduction. Cellular senescence caused by telomere shortening has been suggested as one potential causal agent of aging. In some tissues, telomeres are maintained by telomerase. The presence of telomerase promotes tumor formation however, suggesting a trade-off between aging and cancer. Weinstein and Ciszek's reserve-capacity hypothesis (2002) suggests that the strategies organisms have evolved to cope with this trade-off may vary with lifespan.

Keywords: bird, telomerase, telomere, aging, lifespan

Problems of health for fourth age in Albania

Authors: E.Y. Haveri, A. Xhikneli

To help older people in our country, the Albanian Association Gerontology-Geriatrics (A.A.G.G.) was established in October 1991. The Association represents Albania in the International Gerontology (I.A.G.) and in the other European and World organizations that advocate for problems of "third age". During this period, the Association has organised many activities for its members and the public at large. The tradition in Albania is that responsibility for parents' care lay firmly sons, while married daughters look afer their frail parents.

Keywords: mondi, , , ,

Modification of IL-7 and its use in the treatment of thymic involution

Authors: S.M. Henson, R. Aspinall

Thymic involution is one of many events that leads to the inefficient functioning of the elderly immune system, causing an increased susceptibility to numerous infectious diseases. This loss of immune function, can be in part characterized by the loss of the cytokine IL-7.

Keywords: IL-7, CCR9, fusion protein, therapy, thymic involution

The Role of Nutrition in Human Health, Disease, and Aging - A Practical Approach

Authors: C.B. Heward
Audio: (Audio) (Slides)

The importance of diet and nutrition in human health and disease is well established. Basic laboratory research, clinical trials, and epidemiological studies have all contributed to our understanding of the minimum daily requirements (MDR) for both micro- and macro-nutrients necessary for survival and disease prevention. Caloric restriction experiments in a variety of species have also suggested a connection between diet and aging.

Keywords: nutrition, health, longevity, oxidative stress, phytochemicals

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

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

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 ,

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

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: , , , ,

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

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

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

Genetic and environmental determinants of aging and longevity: the lesson of the life-extending mutations

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

Most studies of aging are conducted in humans and domestic or laboratory animals, i.e. in conditions where artificial environment protection is applied. This yields changes in physiology and behavior, which set up organism's state unobserved in wild life.

Keywords: Life-extending mutations, Aging plasticity, Environmental influences , ,

Telomere shortening: is it really basic cause of senescence?

Authors: A.V. Khalyavkin

Recent hypothesis connects the origin of aging with telomere loss due to "end-replication problem" of linear chromosomes. It is interesting that in some cases the mutant cells which lost all telomeric DNA sequences became immortal, because all chromosomes in these cells became circular. The mechanism of chromosome circularization is not yet known since despite progress in understanding the structure and function of individual genes, little is known about the chromatin structure beyond the level of the nucleosome.

Keywords: Telomere-related aging hypothesis, Intrachromosomal telomeric sequences , , ,

What is the age of the age-related mutations in mitochondrial DNA?

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

The Mitochondrial Theory of Aging postulates that mutations in mitochondrial DNA accumulate with age and cause various intracellular adverse effects that ultimately contribute to some age-related degenerative changes. It is usually assumed that the mutations in question are actually generated at old age. Analysis of mutational spectra (i.e. frequency distributions of mutations by kind), however, suggests that at least in some cases mutations that are observed at old age may have been originally generated early in the development.

Keywords: mitochondrial DNA, aging, mutation, clonal expansion ,

Effect of Physical Activity Levels on Bone Strength

Authors: K. Kikkawa

INTRODUCTION: Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly adequate physical activity in addition to attention to diet. A number of physical educational opinions are available to health care providers. This study examines whether regular exercise has the potential of positively affecting the aging process in Japanese adults with regard to bone strength.

Keywords: ANCOVA, Japanese, Exercise, Ultra-sound method ,

Iron Accumulation During Cellular Senescence

Authors: D.W. Killilea, S.L. Wong, H.S. Cahaya, H. Atamna, B.N. Ames

Iron accumulates as a function of age in many tissues and is associated with age-related pathologies. Although the molecular basis of this change is not known, it may be due to a loss of iron homeostasis at the cellular level. Therefore, changes in iron content in primary (IMR90) and SV-40-transformed (SV-IMR90) human fibroblast cells were studied in culture as a model of cellular senescence. Total iron content increased exponentially in IMR90s during cellular senescence, whereas iron content in SV-IMR90s remained unchanged under identical conditions.

Keywords: senescence, iron, oxidative stress , ,

Genetic correction of mitochondrial respiratory chain deficiencies

Authors: M.P. King
Audio: (Audio)

Increasing numbers of patients are being identified as suffering from mitochondrial diseases. Such diseases display great diversity in clinical symptoms and morphological and biochemical characteristics. Although mtDNA mutations have been identified in many patients, there are presently no effective treatments. A number of human diseases result from mutations in mtDNA-encoded proteins, a group of proteins that are hydrophobic and have multiple membrane-spanning regions.

Keywords: mtDNA, mitochondria, respiratory chain, mitochondrial disease ,

Intestinal stem cell ageing: role of mitochondrial mutation?

Authors: T.B.L. Kirkwood
Audio: (Audio)

We have shown that important functional changes occur with ageing in the stem cells of murine intestinal epithelium, resulting in increased susceptibility to damage-induced apoptosis, impaired regenerative capacity, and altered DNA damage responses. More recently, in studies of human colonic epithelium we have described a surprisingly high burden of mtDNA mutation that increases strongly with age and appears to originate within the stem cells.

Keywords: Ageing, Stem Cells, Intestinal Epithelium, Mitochondrial Mutation ,

Zebrafish as a novel vertebrate model of functional aging and gradual senescence

Authors: S. Kishi, J. Uchiyama

The zebrafish (Danio rerio) has been developed as a powerful model for genetic studies in developmental biology, which give insights into several human diseases such as cardiovascular disease and cancer. Because aging processes affect these and many other human disorders, it is important to compare zebrafish and mammalian senescence. However, the aging process of zebrafish remains largely unexplored, and little is known about functional aging and senescence in zebrafish.

Keywords: Zebrafish, aging, senescence, stress, telomerase

Interventions in aging and age-associated pathologies by means of nutritional approaches

Authors: K. Kitani, T. Yokozawa, T. Osawa
Audio: (Audio)

The "Free Radical Theory of Aging" (FRTA) initially proposed by Harman [1]) half a century ago has been increasingly supported in recent years. However, while there have been a number of studies demonstrating a significant effect of antioxidant treatment in preventing experimentally induced pathologies that are believed to be at least partially caused by oxygen induced tissue damage, so-called antioxidant strategies have not been shown convincingly to be effective in increasing life spans of animals [2]).

Keywords: mice, life span, tetrahydrocurcumin, green tea polyphenol, antioxidants