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.

The Microbiological Foundation for Bioremediating Intracellular Aggregates

Authors: B.E. Rittmann
Audio: (Audio)

Several major diseases of old age, including atherosclerosis, macular degeneration, and neurodegenerative diseases, are associated with the intracellular accumulation of substances that impair cellular function and viability. A radically new approach is to augment humans' natural catabolic machinery with microbial enzymes, since natural environments contain microorganisms with a wide range of biodegradation capabilities. Completely biodegrading complex organic materials demands many steps of hydrolysis and oxidation.

Keywords: Bioremediation, Microarray, Fingerprinting, Intracellular, Aggregates

Macroautophagy upregulation - a candidate therapeutic strategy to enhance clearance of toxic intracellular aggregate-prone proteins

Authors: D.C. Rubinsztein
Audio: (Audio)

The deposition of protein aggregates in specific target organs is a feature of many human diseases referred to as Protein Conformation Disorders (PCD). These include Alzheimer's disease, Parkinson's disease, Huntington's disease (HD) and Oculopharyngeal muscular dystrophy (OPMD). The role of aggregates in these diseases has been a subject of vigorous debate. However, irrespective of the nature(s) of the toxic species, it is desirable for cells to be able to control the levels of these toxic proteins and restrict their accumulation.

Keywords: Huntington's disease, macroautophagy, autophagy, polyglutamine ,

Enhanced reprogramming to facilitate production of somatic cell NT ES cell lines

Authors: A. Rybouchkin, Y. Kato, Y. Tsunoda
Audio: (Audio)

One of the limiting factors in production of the human somatic cell nuclear transfer embryonic stem (ntES) cell lines is the paucity of the donor oocyte source and furthermore rather ineffective use of these oocytes for production of NT blastocysts (starting material for ES cell derivation). Indeed, while currently available culture media allow obtaining about 60-70% of blastocysts from in vitro fertilized human oocytes, at present only 25-30% of NT blastocysts obtained after transfer of fibroblast or cumulus cell nuclei can develop to blastocyst stage.

Keywords: therapeutic cloning, nuclear transfer, embryonic stem cells, ,

Telomere dynamics and telomerase-inhibitor cancer therapy

Authors: C.K. Sanders, K.B. Blagoev and E.H. Goodwin

Normal human somatic cells have little or no telomerase activity. Consequently their telomeres grow shorter with each cell division. These cells senesce when their telomeres become too short to protect chromosome ends. In contrast to normal cells, nearly all human tumors avoid senescence by maintaining adequate telomere length. About 85% of tumors reactivate telomerase, and ~15% utilize a poorly understood mechanism called "alternative lengthening of telomeres (ALT)" that is associated with elevated recombination rates particularly within telomeric DNA.

Keywords: telomere, telomerase, ALT , ,

Telomerase decreases ROS levels but does not counteract telomere shortening under oxidative stress

Authors: S.S. Ahmed, J. Passos, T. von Zglinicki, G.C. Saretzki
Audio: (Audio)

Oxidative damage is thought to be a major cause for replicative senescence and human ageing. We and others have shown that external modulation of oxidative stress levels can modify telomere shortening rates and the replicative life span of a given cell culture. Hyperoxia (40% oxygen partial pressure) accelerates production of reactive oxygen species mitochondrial respiration and increases telomere shortening dramaticly.

Keywords: senescence, oxidative stress, telomerase, hTERT, mitochondria

Aging Research Enabled by Patient-Specific Embryonic Stem Cells Derived from Human SCNT-Blastocysts

Authors: W.S. Hwang, S.I. Roh, B.C. Lee, S.K. Kang, D.K. Kwon, S. Kim, S.J. Kim, S.W. Park, H.S. Kwon, C.K. Lee, J.B. Lee, J.M. Kim, C. Ahn, S.H. Paek, S.S. Chang, J.J. Koo, H.S. Yoon, J.H. Hwang, Y.Y. Hwang, Y.S. Park, S.K. Oh, H.S. Kim, J.H. Park, S.Y. Moon, G. Schatten
Audio: (Audio)

Aging research and the biology of sensence may benefit from the efficient derivations of human embryonic stem cells derived from cloned blastocysts. Patient-specific, immune-matched human embryonic stem cells (hESC) are anticipated to be of great biomedical importance for studies of disease and development, and to advance clinical deliberations for stem cell transplantation. Eleven hESC lines were established by nuclear transfer (SCNT; NT) of skin cells from patients with disease or injury into donated oocytes.

Keywords: Human Embryonic Stem Cells, Nuclear Transfer, Aging , ,

Sustained Stromal Stem Cell Self-Renewal and Osteoblastic Differentiation During Aging

Authors: P.C. Schiller, G. D'Ippolito, G.A. Howard, B.A. Roos
Audio: (Audio)

We have identified and partially characterized a population of normal marrow-isolated adult multilineage inducible (MIAMI) cells from males and females 3- to 72-years-old. These primitive cells are characterized by the expression of Oct4, Rex1, cMet, Nrtk3, BMPR1B, CD29, CD63, CD81, CD122, and CD164 among other molecules. Although the frequency of MAIMI cells, among all marrow nucleated cells, decreases from 0.01% at age 3 to 0.0018% at age 45, their numbers appear to remain unchanged after this age.

Keywords: , , , ,

Immunomodulatory vaccines against autoimmune diseases

Authors: M. Sela
Audio: (Audio) (Slides)

Vaccines are for healthy people, to prevent them from becoming ill. Such prophylactic vaccines have been a great success. Therapeutic vaccines become more and more important, especially as life expectancy rises. Efforts to develop such vaccines against cancer, AIDS, hepatitis, tuberculosis, Alzheimers disease, mad cow disease, etc. have not yet reached the stage where they can be successfully used on a daily basis.

Keywords: , , , ,

Mice with improved systems for cellular quality control: super-p53 and super-p16/ARF mice

Authors: M. Serrano, I. Garcia-Cao, M. Garcia-Cao, A. Matheu, M.A. Blasco
Audio: (Audio)

We are interested in testing the effects of increasing the gene dosage of critical tumor suppressors in mice to evaluate the consequences on cancer, aging and general organismal fitness. The tumor suppressors p53 and p16/ARF are among the most important sensors of stress, their activation is meant to eliminate damaged cells and thus prevent the appearance of tumors. Aging has long been considered to be the result of the accumulation of cellular damage.

Keywords: p53, p16INK4a, ARF, cancer, stress

Tissue Engineering Teeth

Authors: P.T. Sharpe
Audio: (Audio)

Most organs start their development in the early embryo from interactions between epithelial and mesenchymal cells. The nature of the signalling pathways and their downstream targets that mediate these interactions are increasingly well-understood. Mammalian teeth develop from a reciprocal series of interactions between embryonic oral epithelium and neural crest-derived mesenchyme. The first instructive signals come from the epithelial cells which act to initiate the tooth forming process and to regulate the temporo-spatial expression of transcription factor genes in the mesenchyme.

Keywords: stem cells, teeth, tissue engineering , ,

Ageing and oral health related to quality of life

Authors: N. Shtereva

Oral health is more than healthy teeth. Oral diseases and disorders can affect general health, well-being and quality of life.

The goal of this investigation is to establish oral health related to quality of life of geriatric patients.

Keywords: oral health, quality of life, geriatric patients, assessment, ageing

Microheteroplasmy and protofection - the why and how of mtDNA replacement therapy

Authors: R. Smigrodzki
Audio: (Audio)

Doubts about the relevance of mitochondrial mutations for aging and disease usually concentrate on their low frequency found in some studies. Recently, an enormous mutation burden (microheteroplasmy) was discovered with more sensitive detection methods. In the aged adult the vast majority (more than 99%) of mitochondrial genomes are mutated. The biochemical pathways linking them to the aging phenotype are increasingly being elucidated as well.

Keywords: , , , ,

Clinical Application of Umbilical Cord Blood Mesenchymal Stem Cells

Authors: C.H. Song
Audio: (Audio)

A stem cell is a special kind of cell that has a unique capacity to renew itself and to give rise to specialized cell types. Although most cells of the body,such as heart cells or skin cells,are committed to conduct a specific function, a stem cell is uncommitted and remains uncommitted, until it receives a signal to develop into a specialized cell. Their proliferative capacity combined with the ability to become specialized makes stem cells unique. Researchers have for years looked for ways to use stem cells to replace cells and tissues that are damaged or diseased.

Keywords: Umbilical Cord Blood, Mesenchymal Stem Cell , , ,

The Lipofuscin of the Retinal Pigment Epithelium

Authors: J.R. Sparrow
Audio: (Audio)

Non-degradable autofluorescence pigments that accumulate in the retinal pigment epithelium (RPE) are implicated in the death of RPE cells in juvenile onset (Stargardt) macular degeneration and in the atrophic form of age-related macular degeneration. Our efforts are directed toward understanding the structures of these compounds, their biosynthetic pathways, factors that promote their formation and mechanisms by which they may damage the cell.

Keywords: retinal pigment epithelium, lipofuscin, retinoid-adducts, retinal degeneration ,

To Make an New Intestinal Mucosa

Authors: M. Stelzner
Audio: (Audio)

A number of clinical conditions are caused by disorders affecting the mucosal lining of the gastrointestinal tract. Some patients suffer from a loss of mucosal surface area due to congenital defects or due to surgical resections ("short bowel syndrome"). Other patients have inborn or acquired defects of certain mucosal functions (e.g., glucose galactose malabsorption, bile acid malabsorption). Many patients with these mucosal disorders could be more effectively treated if healthy mucosa were available in larger quantities as a replacement or functional supplement.

Keywords: , , , ,

Senescence in mesenchymal stem cells: the effects of reduced culture temperature and media glucose concentration

Authors: A. Stolzing, A. Scutt

Mesenchymal progenitor cells (MPC) show great promise for use in a variety of cell-based therapies. As isolated primary MPC are low in numbers, in vitro expansion is necessary. However the expansion potential is limited and in vitro aging leads to loss of multipotency and to replicative senescence. Stress induced by the culture conditions is thought to be one of the driving reasons for replicative senescence and might also influence multipotency of MPC. Optimisation of culture conditions might be able to improve the expansion of MPC in cultures.

Keywords: mesenchymal stem cells, aging, senescence, ,

Apoptosis, genome maintenance, and aging

Authors: Y. Suh
Audio: (Audio)

Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Apoptosis in response to DNA damage, a major tumor suppressor mechanism, is antagonistically pleiotropic, promoting the development of specific ageing phenotypes as well as suppressing the development of cancer. This is illustrated by reduced spontaneous tumor formation and premature appearance of other aging-related phenotypes in several mouse mutants harboring genetic defects in genome maintenance.

Keywords: apoptosis, genome, aging, ageing phenotype ,

The Impact of Aging on CD4 T Cell Function

Authors: S. Swain
Audio: (Audio) (Slides)

As people age their ability to be successfully immunized by vaccination declines. We have found that the ability of naïve CD4 T cells to respond and develop into effector and memory cells declines markedly with age. To analyze the extent of the CD4 defect, we have used an adoptive transfer model so that we can focus on the defect in the naïve T cell population. We transfer T cell receptor transgenic naïve T cells from aged mice into young T depleted hosts and examine the response of the aged donor T cells compared young T cells.

Keywords: , , , ,

Immune Tolerance Induction: From Bench to Bedside

Authors: M. Sykes
Audio: (Audio) (Slides)

Allograft tolerance, meaning a state in which the immune system regards a donor graft as "self", is the "holy grail" of research in transplantation. Tolerance would avoid the need for chronic immunosuppressive therapy, with all of its toxicities, that is currently required to prevent graft rejection. Tolerance would also prevent chronic rejection, the major cause of late graft loss, which remains a major problem despite recent improvements in immunosuppressive drugs.

Keywords: , , , ,

Is thrombolytic therapy effective in elderly patients?

Authors: E. Taneva

Thrombolytic therapy (TT) is applied in patients with Acute Myocardial Infarction (AMI) with ST-segment elevation, but there is an age limitation - not more 75 years old. It is recommended PTCA or by-pass surgery to elderly patients. For PTCA and by-pass surgery there has to be a prepared cardio-surgery medical team, which can be find in big medical hospitals. Patients with AMI with ST-segment elevation over 75 years, which has no TT applied, are with suspicious prognosis for longevity and quality of life.

Keywords: elderly, acute myocardial infarction, thrombolytic therapy , ,

Thymic Rejuvenation by Engineered Cells Secreting IL-7 in situ

Authors: J.A. Phillips, E.L. Virts, M.L. Thoman

With advancing age the mammalian thymus undergoes involution, a progressive loss of architectural integrity and lymphoid cellularity that results in reduced T lymphopoiesis. Thymic involution is frequently associated with states of immune deficiency, such as active HIV infection, or severe malnutrition as well as advanced age. Immune recovery appears to require restoration of normal thymopoiesis.

Keywords: Thymopoiesis, IL-7, Involution, ,

Leptin and Longevity: Blocking the consequences of lipid overload

Authors: R.H. Unger
Audio: (Audio)

Leptin mediates intracellular liporegulation in nonadipocytes and adipocytes, and, by maintaining intracellular homeostasis, influences the ability of cells to withstand disease-causing environmental perturbations. Leptin effectively partitions FA surplus into adipocytes through its central action, which limits the magnitude of overnutrition to fit into the slowly expanding adipocyte storage space, and through a peripheral action to increase oxidation of surplus fatty acids (FA).

Keywords: , , , ,

Cellular ageing in fibroblast cultures from elderly aged 90 years old

Authors: A.B. Maier, R.G.J. Westendorp, D. van Heemst
Audio: (Audio) (Slides)

The typical growth of primary fibroblast cultures is characterized by three different phases. After initiation of the culture (phase 1), cells rapidly proliferate (phase 2). Hereafter the growth rate starts to decline (phase 2b), followed by degeneration of the culture (phase 3). The commitment theory explains the finite lifespan and predicts that cells become senescent with some fixed probability after a specific number of cell divisions. The population growth rate drops when the first committed cell stops dividing and the culture enters senescence if the last cell becomes postmitotic.

Keywords: cellular, ageing, senescence, fibroblasts, human

nACHR4 594C/T SNP in Alzheimer Disease

Authors: S. Vasto, D. Nuzzo, F. Listì, C.R. Balistreri, D. Di Carlo, V. Ditta, M.P. Grimaldi, D. Lio, C. Franceschi, G. Candore, C. Caruso

Alzheimer disease is the most common form of dementia with complex aetiology and multifactorial origin. In the brain of Alzheimer patients there same common features like: β/A4 (APP) precipitation, tau phosphorylation, spindle and network formation, and degeneration of colinergic neurons in the basal fore brain. The nicotinic achetilcolinic receptor (nAChR) belongs to the superfamily of ionic channel activated by ligand. These proteins have pentameric trans-membrane structure with either effector either receptor function.

Keywords: Alzheimer disease, nAChR, Polymorphism , ,

Genome Structure May Control Lifespan

Authors: B. Villeponteau

Many studies have shown that the insulin pathway is critical to lifespan in all species that have been tested. The key protein in the insulin pathway is Daf16 in C. elegans or Sirt1 in humans. Daf16 and Sirt1 are histone deacetylase enzymes that promote gene silencing by altering chromatin folding. Recently, the insulin pathway has been implicated as central to the ability of caloric restriction to extend lifespan. The telomeric ends of chromosome are also critical to lifespan in C. elegans and the preliferative lifespan of human cells in culture.

Keywords: chromatin, aging, lifespan, telomeres, insulin

Deciphering Free-Radical Code of Aging

Authors: S. Volovik

Free radicals (especially ROS, RNS, RSS, and RCS) are evolutionally archetypal, ubiquitous, and omnipotent in physiological and pathophysiological processes. Classical free-radical paradigm in aging and age-related pathologies, focused in essence on oxidative cellular damage, in order to resolve the problem of free radicals physiological-detrimental dichotomy, decipher genuine triggering mechanisms of aging, and grasp subtle molecular ways of intervention, needs new expansions, conceptualization, and generalization.

Keywords: free-radical paradigm in aging, free radicals chemical and physiological ambivalence and complementarity, free-radical dynamic redox homeostasis, redoxomics ,

Factors that might affect the allotopic replacement of a damaged mitochondrial DNA-encoded protein

Authors: S.J. Zullo J.M. Eisenstadt, C.R. Merril, H. Weiner
Audio: (Audio) (Slides)

We recently demonstrated that by changing codons of an oligomycin-resistant mutant mitochondrial DNA (mtDNA)-encoded ATPase 6 gene, it was possible to express it from the nucleus. Further, if constructed with a mitochondrial-targeting leader sequence, this protein was transported into mitochondria of CHO cells and conferred oligomycin resistance to a cell line that possessed a normal mtDNA ATPase 6 gene sequence (Zullo et al. Rejuvenation Research 8, 18-28, 2005).

Keywords: allotopic, mitochondria, protein import, mtDNA ,

Strategies for the Reversal of the Aging of Human Somatic Cells

Authors: M.D. West, I. Klimanskaya, R.P. Lanza
Audio: (Audio)

An increasing number of the manifestations of aging are being attributed to telomere shortening and/or damage. Nuclear transfer offers the possibility of transiently reactivating telomerase activity, restoring germ-line telomere length, exchanging the somatic cell mitochondria with that of the oocyte, and reprogramming the chromatin of somatic cells to an embryonic pattern of gene expression.

Keywords: Stem Cells, Telomeres, Telomerase, Nuclear Transfer, Mitochondria

Tackling the diseases of old age; progress towards an Alzheimer's therapeutic

Authors: S.M. Wilson, J. Patel, S. Dealler, R. Rosedale, C.J. Stanley
Audio: (Audio)

Any major improvements to lifespan are likely to increase the prevalence of age related diseases such as Alzheimer's Disease (AD). AD is almost exclusively a disease in those aged 65 or older and the prevalence increases with age. It is predicted that even with today's ageing population the prevalence of AD will increase significantly. In AD the brain has a number of changes that can be linked to pathology including aggregates of tau and beta amyloid proteins.

Keywords: Alzheimer's, aggregates , therapy , ligand ,

Can a single subunit NADH dehydrogenase rescue complex I defects?

Authors: T. Yagi, B.B. Seo, E. Nakamaru-Ogiso, T.R. Flotte, A. Matsuno-Yagi
Audio: (Audio)

It has been recognized that structural and functional defects of human mitochondrial NADH dehydrogenase (complex I) are involved in many diseases. Recently, sporadic Parkinson's disease and type 2 diabetes due to obesity are also considered to be related to complex I defects. Therefore, it seems important to develop therapies for complex I defects. Mitochondria of Saccharomyces cerevisiae lack complex I but instead have the rotenone-insensitive internal NADH dehydrogenase (Ndi1). The Ndi1 enzyme is composed of a single polypeptide and lacks proton pumping function.

Keywords: NADH dehydrogenase, mitochondrial disease, therapy, complex I,

Nanog changing in mouse kidneys with age

Authors: Q.-J. Yan, X.-M. Chen, Y.-M. Zhang, Y. Xie, S.-Z. Shi, B. Fu, Q. Hong, G.-S. Xu, X.-G. Zhang, H.-Y. Zhu, D. Wu, Y. Lv, Y.-H. Zhang

Nanog has been discovered that is essential for mouse and human embryonic stem cells (ESC) pluripotency and self-renewal. It also expressed in several adult murine tissues by using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. However, human Nanog transcripts have been isolated from adult bone morrow (EST, BF893620). Here, we study the Nanog gene expression profiling in the isolated mouse renal papillary cells that were confirmed by assessment of expression by Northern blots, RT-PCR.

Keywords: Nanog gene, Senescence, kidney, ,

Nuclear insulin-like growth factor binding protein-3 induces apoptosis and is targeted to ubiquitin/proteasome-dependent proteolysis

Authors: W. Zwerschke
Audio: (Audio)

Insulin-like growth factor binding protein-3 (IGFBP-3), the product of a tumor suppressor target gene, is associated with cellular senescence and can induce apoptosis by IGF-I-dependent and -independent mechanisms. IGFBP-3 controls the bioavailability of IGFs in the extracellular environment and is known to be subject to degradation by various extracellular proteases. We show here that IGFBP-3 exists as nuclear protein in situ in human osteosarcoma tissue.

Keywords: , , , ,