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.

Formation and damaging effects of superoxide in mitochondria: relevance to mitochondrial aging

Authors: I.B. Afanas'ev
Audio: (Audio) (Slides)

Mitochondrial formation of superoxide has been recognized for a long time: it is believed to be equal to about 3% of total electron flux, although this amount has never been experimentally proven. It is also frequently accepted that ubiquinone is a source of superoxide production in mitochondria. However, comparison of the one-electron reduction potentials of ubiquinones and dioxygen and a great excess of ubiquinone relatively to the other mitochondrial electron carriers suggest that the equilibrium of reaction between ubiquinone and dioxygen must be shifted to the left, i.e.

Keywords: superoxide, mitochondria, aging

Adrenal cortex macrophages during ageing and after dexamethasone administration

Authors: H. Almeida, J. Ferreira, D. Neves

A known function of macrophages is to remove dead cells. In the adrenal cortex (AC), macrophages are mainly observed in the zona reticularis (ZR), situated deep in the gland. This finding is in agreement with the theory that AC parenchyma cells originate in the outer layers and migrate to the ZR where they die and are eliminated.

Keywords: adrenal, macrophage, ageing, dexamethasone

Delaying the Mitochondrial Decay of Aging

Authors: B.N. Ames
Audio: (Audio) (Slides)

Mitochondria decay with age due to oxidation of RNA/DNA, proteins, and lipids. Oxidative mitochondrial decay is a major contributor to aging. We are making progress in reversing some of this decay in old rats by feeding them normal mitochondrial metabolites (acetyl carnitine and lipoic acid) at high levels (1-3). The principle behind this effect appears to be that with age increased oxidative damage to protein causes a deformation of structure of key enzymes, with a consequent lessening of affinity (Km) for the enzyme substrate.

Absolute Versus Relative Caloric Intake: Clues To The Mechanism Of Calorie/Aging-rate Interactions

Authors: R.M. Anson

Two fundamental questions confront biogerontologists working with caloric or dietary restriction: (1) How does food intake influence the rate of aging? (2) Should people practice caloric restriction while awaiting the answer to question #1? (In other words: does it work in humans, and if so, is it safe and practical?) This presentation will review the evidence from several laboratories that absolute caloric intake does not matter in terms of aging rate and will discuss ways in which this evidence suggests approaches to finding the answers to these questions.

Keywords: lifespan , calories, restriction , aging , longevity

The biomedical relevance of microbial catabolic versatility

Authors: J.A.C. Archer
Audio: (Audio) (Slides)

Degenerative metabolic markers such as lipofuscin or atheroma may be considered as classes of 'dead-end' substrates within the limited mammalian metabolism. However, some microbial enzyme pathways are very much more diverse and in some cases may be able to convert such substrates into metabolically useful products. Recent genomic studies and cell assays indicate that mycolic acid bacteria from the genus Rhodococcus can metabolise such compounds.

Keywords: lipofuscin , atherosclerosis , Rhodococcus , catabolism

Alpha lipoic acid increases sodium potassium ATPase and reduces lipofuscin accumulation in discrete brain regions of aged rats

Authors: P. Arivazhagan, D. Ayusawa, C. Panneerselvam

A convincing link between oxidative stress and neurodegenerative condtions has been made with the knowledge that oxidative changes may actually trigger deterioration in cellular functions. We analysed the effect of DL-alpha-lipoic acid on the level of lipofuscin and the activity of sodium pottasium ATPase in discrete brain regions of young and aged rats. In aged rats, the level of lipofuscin was high, while the activity of sodium potassium ATPase was low.

Keywords: alpha lipoic acid, ageing, lipofuscin

Gene Networks, Individual Senescence, and Timeless Aging

Authors: R. Arking, C.N. Giroux

The genetic analysis of aging has dramatically improved our understanding of the aging process by highlighting the role of longevity determinant mechanisms (e.g., the insulin-like signaling pathway). But there are important remaining difficulties. We need to explain how the aging process can utilize highly conserved common mechanisms, yet still be expressed as a highly individual process. We need to better understand how these mechanisms interact with the environment and the individual life history. We need to develop an alternative to the use of time as a measure of aging.

Keywords: gene networks, senescence, health span, oxidative stress networks

The Magnificent IL-7; an interleukin for rejuvenating the immune system

Authors: R. Aspinall, S. Henson, J. Pido-Lopez, P.T. Ngom
Audio: (Audio)

Infection by a virus of an individual (aged 20-30) will cause a response from the T (thymus derived) lymphocytes of which there are approximately 3 x 1011. If the individual has not met the virus before, the response will come from the naïve T cell subset (50±10% of the total T cell pool at this age) containing recent thymic emigrants produced from the thymus at approximately 108 per day. Their antigen specific receptor has a defined specificity governed by the conformation of its 2 chains (?

Social, Political, and Ethical Obstacles to Human Life Extension

Authors: S.N. Austad
Audio: (Audio) (Slides)

The Preamble to the Constitution of the World Health Organization states that "the enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being?." From that perspective, one might expect exceptional public enthusiasm and support for research into medically-induced longer, healthier human life. However, such enthusiasm and support has been marginal, especially compared to the much greater support and enthusiasm for medical research campaigns against specific late-life diseases such as cancer and diabetes.

The extent and significance of telomere loss with age

Authors: D.M. Baird, D. Kipling

By imposing a limit on the proliferative lifespan of some human cell types, telomere loss and the subsequent onset of replicative senescence has been proposed to contribute to age related disease. Whilst there is a large of body of in vitro data to reveal the mechanisms by which telomere erosion triggers senescence, technical limitations have hampered our ability to understand the full extent of telomere erosion in vivo.

Keywords: telomere, telomerase, ageing

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

Authors: Z. Bandpey, J. Herbert

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

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

Oxygen Radicals and Aging

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

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

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

Cellular Nutrient Sensing and Longevity

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

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

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

Comparative estimation of adaptation biomarkers

Authors: L.M. Belozerova

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

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

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

Decay of mitochondrial metabolic competence in the aging cerebellum

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

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

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

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

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

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

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

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

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

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

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

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

Authors: D. Broccoli
Audio: (Audio)

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

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

New limbs for old - lessons from the newt

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

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

Keywords: regeneration, urodele, heart, lens, plasticity

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

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

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

Keywords: dwarf mice, glutathione, growth hormone , ,

Testing the Free Radical Theory of Ageing in Bats

Authors: A.K. Brunet-Rossinni

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

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

Aging of cardiac myocytes and mitochondrial turnover

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

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

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

Selective vulnerability in ageing rat sympathetic neurons

Authors: K.P. Gatzinsky, C. Thrasivoulou, M. Campioni-Noack, C. Underwood, T. Cowen

We have examined the hypothesis that differences in NGF uptake and transport determine vulnerability to age-related neurodegeneration. Neurons projecting to cerebral blood vessels (CV) have been found to be more vulnerable to this kind of degeneration than those projecting to the iris. Uptake of NGF was therefore examined in sympathetic neurons projecting from the superior cervical ganglion (SCG) to CV and iris in young and old rats by treating the peripheral processes of these neurons with different doses of I125-NGF.

Keywords: neurodegeneration, SCG, iris, cerebral blood vessels, NGF

Consequences of cellular senescence and prospects for reversal

Authors: J. Campisi
Audio: (Audio) (Slides)

Normal cells can respond to DNA damage, telomere dysfunction, and other potentially oncogenic events by entering an essentially irreversible state of arrested growth and altered function termed cellular senescence. Multiple lines of evidence indicate that the senescence response is an important mechanism for preventing the development of cancer among mammals. However, there is also evidence that cellular senescence may be an example of evolutionary antagonistic pleiotropy.

Keywords: tumor suppression, antagonistic pleiotropy, cellular senescence, cancer, aging

Mouse Models and Human Aging

Authors: M.R. Capecchi
Audio: (Audio)

Gene targeting provides the means for creating strains of mice with designed alteration in any chosen genetic locus. This technology permits the evaluation of the functions of genes in the intact mammal and the systematic dissection of the most complex biological processes from embryogenesis to aging.

Keywords: mouse models of human aging , , , ,

Mr. Yuck meets the Grim Reaper: why living longer is not such a bad thing

Authors: A. Caplan
Audio: (Audio) (Slides)

Leon Kass, the Chair of President Bush's bioethics council maintains that efforts to extend human life are inherently immoral. He is not alone in this opinion. Daniel Callahan, Francis Fukuyama and Gilbert Meilander among others maintain that the drive to extend the human life span is wrong.

Keywords: finitude, ethics, life-extension, ,

Looking for immunological risk genotypes

Authors: C. Caruso, A. Aquino, G. Candore, L. Scola, G. Colonna-Romano, D. Lio

Some people live in good health to great ages while others die relatively young, though we do not understand why this is so. However several studies show that longevity may be correlated with optimal functioning of the immune system. In fact, both longitudinal and cross-sectional studies performed in the last years have indicated that several functional markers of immune system may be used either as markers of successful ageing or conversely as markers of unsuccessful ageing.

Keywords: lymphocyte, IL-10, IFN-gamma, marker ,

Vitamin E-deficiency and aging effect on expression levels of GAP-43 and MAP-2 in selected areas of the brain

Authors: T. Casoli, G. Di Stefano, A. Delfino, C. Bertoni-Freddari

The most widely accepted physiological function of vitamin E is its role as an important antioxidant in membranes, preventing oxidative damage to polyunsaturated lipids in the lipid bilayer. The brain is thought to be particularly vulnerable to oxidative stress due to its high rate of oxygen consumption along with its poor catalase activity and moderate amounts of superoxide dismutase and glutathione peroxidase. Moreover, it is known that the neurological abnormalities observed during aging are similar to those observed in vitamin E deficiency.

Keywords: MAP-2, GAP-43, aging, in situ hybridization, vitamin E-deficiency

Measurement of the 4834 bp mitochondrial DNA deletion level by Real Time PCR in aging rat liver subjected or not to caloric restriction diet

Authors: P. Cassano, A.G. Sciancalepore, A.M.S. Lezza, C. Leeuwenburgh, P. Cantatore, M.N. Gadaleta

Aging is a fascinating and highly important topic because of its great social relevance and scientific complexity. One of the most important theories to explain this multifactorial process is the free radical theory. Such theory involves the damaging role of reactive oxygen species (ROS) on mitochondrial molecular components as lipids, proteins and mitochondrial DNA (mtDNA).

Keywords: aging rat, Real Time PCR, caloric restriction, mtDNA deletion ,

A high-throughput screening system for human genes extending life-span

Authors: C. Chen, R. Contreras

We developed a high-throughput functional genomic strategy that allows identification of human genes prolonging life-span in the baker's yeast Saccharomyces cerevisiae. The method is based on isolating yeast mother cells with extended number of cell divisions as indicated by the increased number of bud scars on their surface. Screening of a human HepG2 cDNA expression library in yeast resulted in the isolation of 12 yeast transformants with a potentially prolonged life-span. The transgene in one of the lines was identified as ferritin light chain (FTL) and studied in more detail.

Keywords: aging, lifespan, stress, yeast ,

Excitotoxic neurodegeneration induced by intranasal administration of kainic acid in C57Bl/6 mice

Authors: Z. Chen, H.-G. Ljunggren, N. Bogdanovic, I. Nennesmo, B. Winblad, J. Zhu

Glutamate excitotoxicity plays a key role in inducing neuronal cell death in many neurological diseases, such as Alzheimer's disease. In mice, administration of kainic acid, an analogue of the excitotoxin glutamate, results in hippocampal cell death and seizures. Kainic-acid-induced seizures in mice provide a well-characterized model for studies of human neurodegenerative diseases. However, C57BL/6 mice, which are often used for genetic analyses and transgenic and knockout studies, are resistant to excitotoxicity induced by subcutaneous administration of kainic acid.

Keywords: kainic acid, excitotoxic, neurodegeneration, hippocampus, C57BL/6 strain

Model of aging taking into account packing of cells

Authors: V.E. Chernilevsky, A.N. Zajarny

Purpose, material and methods: The numerical experiment was carried out on a model of organism for valuation mechanisms of aging. Results: The cells (C) were substituted for deformable spheres in limited volume. Proliferation simulated by the doubling of C with the given coordinates.

Keywords: Cellular packing, Aging, , ,

Generally biological approach to a problem of aging

Authors: V.E. Chernilevsky

Purpose: On a basis of the general biological approach to a problem of aging the prospects of life prolongation of the man are studied. Materials and methods:. The comparative analysis of aging of organisms of various systematic groups has been carried. Results: The aging is a decrease of viability organism owing to delay of self-renovation of cells, organs and tissues. The self-renovation - basic property alive, is provided at the expense of system stem cells (SC) during all life.

Keywords: Aging, Life span prolongation , , ,

Lowering of metabolism - a possible method of human life span prolongation

Authors: V.E. Chernilevsky

Purpose: The possibilities of lowering basal metabolism (LBM) in man with aim of longevity have been investigated. The method is based on the data that at many mammalia in state of hypobiosis BM is lowered very much and aging is delyed independently from the mechanisms, and after hypobiosis the process of self-renovation of tissues is activated, In addition the life span of some species (Microtus, Soricidae etc,) is able to increase in several times.

Keywords: Lowered metabolism, Longevity , , ,

Recovery of mitogenic signaling by reduction of caveolin-1 in senescent cells

Authors: K.A. Cho, S.J. Ryu, K.T. Kim, I.S. Jang, S.C. Park

Hyporesponsiveness to growth factors is one of the fundamental characteristics of senescent cells. We previously reported that the up-regulation of caveolin attenuates the growth factor response and the subsequent downstream signal cascades in senescent human diploid fibroblasts (HDF). Therefore, in the present experiment, we investigated the modulation of caveolin status in senescent cells to determine the effect of caveolin on mitogenic signaling efficiency and cell cycling.

Keywords: senescent, caveolin-1, mitogenic signaling, morphology, focal adhesion

Human Supercentenarian Epidemiology and the Implications for Longevity

Authors: L.S. Coles
Audio: (Audio) (Slides)

Perhaps 135,000 years ago, in Africa, the earliest known Homo sapiens were thrust into an intensely-competitive game-of-chance played according to the rules of an indifferent casino. We can only imagine, from our present vantage point, the sort of harsh world our ancestors routinely endured. The other species in this game-of-survival did not hesitate to kill and eat their prey, and we imagine that humans were no exception to this law of the jungle.

Keywords: Supercentenarian, Longevity, Morbidity, Mortality, Lifespan

Gender differences in Alzheimer's disease neuropathology

Authors: E.H. Corder, E. Ghebremedhin, D.R. Thal, T.G. Ohm, H. Braak
Audio: (Audio) (Slides)

Women are thought to have a higher risk of developing Alzheimer's disease (AD) compared to men, partly because they live longer. We investigated whether women have an accelerated pathogenesis of AD which would account for higher age-specific disease occurrence. A total of 3165 men and 2450 women were investigated. Braak stages for neurofibrillary tangles (NFT) (I-VI, recoded 1 to 6 for analysis) and senile plaque (SP) (A-C, recoded 1 to 3) were compared for men and women for each decade of age from 20-29 years onward. Men and women were equally likely to have AD changes at each age.

Keywords: dementia, gender differences, neurodegeneration, Alzheimer disease ,

Pathways to exceptional human longevity: New evidence from the 1982-1999 National Long Term Care Surveys

Authors: L.S. Corder
Audio: (Audio)

Patterns of health and functioning associated with exceptional longevity have not recently been described or analyzed in the United States at the population level. Neither the antecedents of exceptional healthy longevity nor pathways to exceptional longevity have been evaluated. Population forecasts that explicitly consider interventions have yet to be presented.

Keywords: exceptional longevity , physical functioning, population sample , discrete multivariate models ,

Use of zolpidem in over-75 year old patients with sleep disorders and comorbidities

Authors: A. Cotroneo, P. Gareri, S. Cabodi

Quality of sleep is one of the main quality indexes of life and is a remarkable dimension of lived life in elderly population, especially in frail elders having comorbidities and therefore, polytherapy. Sleep is often underevaluated even if it is closely related to individual well-being. This is more marked in the elderly and is often the cause of worsening in quality of life; in particular, sleep is more light, is characterized by several awakenings and is associated to a diurnal somnolence.

Keywords: zolpidem, elderly, sleep, comorbidities ,

Chronic treatment with a precursor of phosphatidylcholine ameliorates morphological and behavioural effects of ageing in the rat hippocampus

Authors: D. Crespo, M. Megias, C. Fernandez-Viadero, R. Verduga

The hippocampal formation (HF) is a brain region that has been most implicated in the age-related memory dysfunction, and it is very vulnerable to the process of ageing. There is some controversy over the structural basis of memory in the hippocampus. The recent investigations reporting the involvement of NO in memory function have paved the way for the analyses of the relations between these NO-neurons and memory.

Keywords: Hippocampus, CDP-Choline, Mice, Memory, Stereology

Non-invasive Human Oxidative Stress Profiling and its Biomedical Application

Authors: R.G. Cutler
Audio: (Audio)

Scientific evidence is steadily accumulating, supporting the general importance of oxidative damage of tissue and cellular components as a primary or secondary causative factor in many different human diseases and aging processes. However, critical evaluation of the role oxidative damage plays in the general health status of an individual and how this damage might be reduced requires better means to measure in vivo by non-evasive means in human patients, their particular status of oxidative damage and related defensive and repair processes.

Keywords: Oxidative Stress Profiling, Antioxidant Status Profiling, Dietary Supplements, Trace Metal Profiling, Inflammatory Marker Profiling

Decline in proteasome and lon protease activity with age: transcriptional dysregulation or inhibitor accumulation?

Authors: K.J.A. Davies
Audio: (Audio)

The Proteasome is an unusually large and complex proteinase found in the cytoplasm and nucleus of all eucaryotic cells. Proteasome has been shown to play several key roles in the appropriate turnover of normal proteins and the selective degradation of abnormal and damaged proteins. These activities give the Proteasome a vital place in cell cycle progression, protection from protein aggregation, antigen presentation, and maintenance of cellular homeostasis.

Keywords: Oxidative stress, Proteasome, Lon protease, Mitochondria, Aging

Collective Suttee: If Not Everyone Can Afford Life-Extension, Does That Mean No One Should Have It?

Authors: J.K. Davis
Audio: (Audio) (Slides)

Many people worry that life-extension will be available only to the prosperous. Does it follow that society should inhibit life-extension research and development, or does it follow instead that society should subsidize life-extension for the have-nots? I will briefly explain why subsidizing life-extension for the have-nots may be easier than it looks.

Keywords: access, distribution, immortality, justice, life-extension

Investigation of the signalling pathways involved in the proliferative life span barriers in Werner Syndrome fibroblasts

Authors: T. Davis, R.G.A. Faragher, C.J. Jones, D. Kipling

Werner Syndrome (WS) fibroblasts enter replicative senescence after a reduced in vitro life span. Although this has been postulated as causal in the accelerated ageing seen in this disease, controversy remains as to whether WS is showing the acceleration of a normal cellular ageing mechanism, or instead the occurrence of a novel WS-specific process. To address this we analysed the signalling pathways responsible for senescence in WS fibroblasts. Cultured WS (AG05229) fibroblasts senesced after ~20 population doublings, with the majority of the cells having a 2N DNA content.

Keywords: Cell cycle control, senescence, human ageing, telomeres, p53

WILT: an ambitious but truly un-escapable anti-cancer therapy

Authors: A.D.N.J. de Grey, S.E. Artandi, F.C. Campbell, I. Dokal, L.J. Fairbairn, G.J. Graham, C.A.B. Jahoda, A.C.G. Porter
Audio: (Audio) (Slides)

Despite enormous effort, progress in reducing mortality from cancer remains modest. Can a true cancer "cure" ever be developed, given the vast versatility that tumours derive from their genomic instability? Here we consider the efficacy, feasibility, and avoidability of side-effects of a therapy that, unlike any available or in development, could never be escaped by spontaneous changes of gene expression: the total elimination from the body of all genetic potential for telomere elongation, combined with stem cell therapies to maintain proliferative tissues despite this handicap.

Keywords: cancer, replicative capacity, telomeres, stem cells, gene targeting

Biogerontologists' duty to discuss timescales publicly

Authors: A.D.N.J. de Grey
Audio: (Audio) (Slides)

Aging is not popular with the general public, and they look to the scientists with the most detailed understanding of aging to provide credible information on how much longer humanity must endure it. Biogerontologists are acutely aware of their consequent responsibility not to suggest unrealistically optimistic timescales for the defeat of aging. However, they seem mostly to be unaware of their converse responsibility -- not to suggest or imply unrealistically pessimistic timescales.

Keywords: real anti-aging medicine, public debate, timescales , ,

Transcriptomic study of H2O2-induced premature senescence of human diploid fibroblasts using a low-density cDNA array

Authors: J.P. de Magalhaes, V. Migeot, V. Mainfroid, F. de Longueville, J. Remacle, O. Toussaint

Normal human diploid fibroblasts (HDFs) stop dividing after a certain number of population doublings (PDs) in vitro. Telomere shortening observed at each cell division eventually leads telomeres to critical lengths, which in turn trigger growth arrest. Telomerase elongates the telomeres can immortalize HDFs without transformation. Stress-induced premature senescence (SIPS) establishes several at 72 h after exposure of HDFs to subcytotoxic concentrations of oxidative stressors such as hydrogen peroxide (H2O2).

Keywords: cellular senescence, fibroblasts, telomeres, gene expression ,

Remodeling of Age- and Diabetes-Related Changes in Extracellular Matrix

Authors: R.C. deGroof
Audio: (Audio)

Organiser's Note: Dr. deGroof was unable to attend the meeting, and consequently his talk was given by Dr. Lakatta.

Keywords: extracellular matrix, AGE, collagen, crosslink, ALT-711

Mitochondrial transcription factor A (TFAM) acetylation and age-related mtDNA and TFAM contents in several rat tissues

Authors: M.M. Dinardo, C. Musicco, V. Pesce, F. Fracasso, F. Milella, A.M.S. Lezza, G. Gadaleta, P. Cantatore, M.N. Gadaleta

Replication and transcription of the mitochondrial genome depend exclusively on nuclear DNA-encoded products. One of these products, mitochondrial transcription factor A (TFAM), plays a complex role in the regulation of both processes: it is required for mtDNA mainteinance and together with two other factors, TFB1 and TFB2, stimulates mitochondrial transcription [1]. Moreover homozygous disruption of TFAM gene and tissue-specific TFAM knockout cause severe respiratory chain deficiency and increased apoptosis in mice embryos [2].

Keywords: aging rat, TFAM, acetylation, mtDNA content ,

Analysis of the Role of p53 in Aging Using Mouse Models

Authors: L.A. Donehower
Audio: (Audio) (Slides)

The p53 tumor suppressor is critical for protecting the cell against the deleterious effects of an array of stresses, including damage induced by reactive oxygen species. Stress-activated p53 can effect one of several antiproliferative outcomes, including apoptosis, cell cycle arrest, or cell senescence.

Keywords: p53, mouse aging model, stem cells, cancer, accelerated aging