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.

Free radical view on aging starting under physiological conditions

Authors: I.B. Afanas'ev

Free radical theory of aging pointed out at major rogues responsible for human aging - reactive oxygen and nitrogen species. This conclusion was supported by many studies, but one of the most important question is still remaining unanswered: How aging processes start in healthy humans who do not suffer from any pathological disorders and all the stimuli of pathological disorders are excluded? Of course it is a purely hypothetical question, but if we can select "the physiological component" of aging initiation, it could be of importance for the understanding of a mechanism of aging.

Keywords: Aging, Free Radicals, Physiological State

The role of mtDNA deletion mutations in sarcopenia

Authors: J.M. Aiken, D. McKenzie
Audio: (Audio)

Considerable muscle fiber loss occurs in quadriceps muscles of mammals with age. Our studies indicate that the molecular basis of this fiber loss is the accumulation of mtDNA deletion mutations within a muscle fiber to levels that result in mitochondrial electron transport system (ETS) abnormalities, intra-fiber atrophy, fiber breakage and fiber loss. If mtDNA deletion mutations play a role in muscle fiber loss with age, a number of testable hypotheses would have to be valid.

Keywords: mtDNA, sarcopenia, muscle, calorie restriction, ETS abnormalities

Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Illness and a Novel Phospholipid Fraction for Clinical Use for Reversing RTF Shift

Authors: Majid Ali, Gary Viole

A large body of evidence links the species of life span and oxidative stress. Not unexpectedly, mitochondria have drawn much attention as the site of that oxidative stress in the aging process. To cite a specific example, extension of murine life span with overexpression of catalase targeted to mitochondria has been shown.

Sex as a division of labour between mitochondria

Authors: J.F. Allen, C.A. Allen
Audio: (Audio) (Slides)

Why is senescence not inherited? We propose that ageing arises from redox chemistry in mitochondria in somatic cells and male gametes, while passive, "template" mitochondria are sequestered in female germ-lines, allowing an indefinite number of accurate mitochondrial replications without damage to the mitochondria, their genomes, or to the cells that carry them [1].

Keywords: aging, mitochondrion, oxidative-phosphoryation, sex, cloning

The Intergenerational Project: Preserving Heritage in a Technological Society

Authors: E. Aphek

For the last six years I have been implementing a program I initiated: The Intergenerational Program: Preserving Heritage in a Technological Environment. In this program young students, grades 5-11, tutor senior citizens at computer and Internet skills and learn from their older students, a chapter in the latter's personal history. Together they write a digital version of the story, scan pictures, albums, and documents, and search for information on the Net as well as in other sources.

Protective efficacy of alpha lipoic acid on acetylcholinesterase activity in aged rat brain regions

Authors: P. Arivazhagan

The purpose of the present investigation was to measure the activity of acetylcholiesterase in discrete regions of young and aged rat brain before and after DL-a-lipoic acid supplementation. Two groups of male albino rats were used in this study (4 and 24 months of age). DL-a-lipoic acid was administered intraperitoneally with a regimen of 100 mg/kg body weight/day using alkaline saline as a vehicle for 7 and 14 days.

Keywords: lipoic acid, ageing, brain and acetylcholinesterase

Tissue Engineering, Stem Cells and Cloning: Current Concepts and Changing Trends

Authors: A. Atala

Selective cell growth and novel biomaterials have led to the engineering of tissues and organs that may be used to restore and maintain normal function. Cells for tissue reconstitution can be derived from the native organ to be replaced, thus avoiding rejection. In situations where normal native tissues are not available, different stem cell sources may be explored. In addition, recent advances in the field of cloning have made it possible to retrieve cells using nuclear transfer techniques.

Poly(ADP-Ribosyl)ation and Telomere Dynamics in Mammalian Cells

Authors: S. Beneke, P. Boukamp, A. Bürkle

We have previously described a positive correlation between poly(ADP-ribosyl)ation capacity of mononuclear blood cells with longevity of mammalian species. Our comparison of purified recombinant human and rat PARP-1 revealed that this correlation might be explained in part by evolutionary sequence divergence. We have also developed molecular genetic approaches to modulate the poly(ADP-ribosyl)ation status in living cells.

Keywords: Poly(ADP-ribosyl)ation, Telomere, Inhibition , ,

Synaptic pathology in the brain cortex of old monkeys as an early alteration in senile plaques formation

Authors: C. Bertoni-Freddari, P. Fattoretti, T. Casoli, G. Di Stefano, B. Giorgetti, Y. Grossi, M. Balietti, G. Perretta

Senile plaques (SP) are alterations of the senile brain particularly prominent in Alzheimers disease (AD). The classical plaque appears as a roughly spherical area in the neuropil consisting of a compact core or of narrow bundles of beta amyloid (bA), between abnormal neurites. Although SP formation is reported to occur over years, in the human brain this process can be studied only at autopsy and this constitutes a great limit to obtain results specifically regarding the steps of SP build up.

Keywords: Plaques, Synapses, Morphometry, Alzheimer disease, Macaca fascicularis

Cytochemical estimation of cytochrome oxidase activity as a morphofunctional mitochondrial check up

Authors: C. Bertoni-Freddari, P. Fattoretti, T. Casoli, G. Di Stefano, B. Giorgetti, Y. Grossi, M. Balietti

A growing body of experimental results is supporting the critical role played by mitochondrial damage in physiological aging and age-related pathologies. This clear awareness has prompted the need of checking the functional state of mitochondria in order to plan adequate intervention strategies to counteract mitochondrial dysfunctions. In this context, the activity of cytochrome oxidase (COX) is presently considered as a reliable marker of neuronal metabolism.

Keywords: Mitochondrial metabolic competence, Cytochrome oxidase, Megamitochondria, COX cytochemistry, Mitochondrial morphometry

Testing mitochondrial metabolic competence by cytochrome oxidase preferential cytochemistry vs. immmunoreactivity of subunit I and IV

Authors: P. Fattoretti, C. Bertoni-Freddari, T. Casoli, G. Di Stefano, B. Giorgetti, Y. Grossi, M. Balietti

Cytochrome oxidase (COX), complex IV of the mitochondrial respiratory chain, is composed of 13 subunits: three encoded by mitochonmdrial DNA (mtDNA) and ten encoded by nuclear DNA. The coordinated expression of both genomes constitutes an early step in the synthesis of the COX enzyme complex, conceivably quantitative estimations of the level of expression of COX subunits may provide clues to identifying precocious alterations of mitochondrial dysfunction.

Keywords: Mitochondrial metabolic competence, Cytochrome oxidase, COX subunit I, COX subunit IV, COX immunohistochemistry

Level and distribution of microtubule associated protein-2 (MAP2) as an index of dendritic structural dynamics

Authors: G. Di Stefano, T. Casoli, P. Fattoretti, M. Balietti, Y. Grossi, B. Giorgetti, C. Bertoni-Freddari

In the fully differentiated adult central nervous system (CNS) neuronal processes need to maintain a fine balance between stability and plasticity. In addition to being very plastic to adapt to the changing environmental stimulation, neuronal wiring diagrams must be also sufficiently stable to accomplish specific functional tasks on which they are tuned. In this dynamic status, the neuronal cytoskeleton and its components (actin filaments, neurofilaments and microtubules together with the respective associated proteins) are reported to play a major and critical role.

Keywords: MAP2, Dendritic structural dynamics, CNS plasticity, Hippocampus, Olfactory bulb

Structural synaptic remodelling in the perirhinal cortex of adult and old rats following object-recognition training

Authors: C. Bertoni-Freddari, D. Platano, P. Fattoretti, B. Giorgetti, Y Grossi, M. Balietti, T. Casoli, G. Di Stefano, G. Aicardi

A computer-assisted morphometric study has been carried out on the synaptic junctional areas of perirhinal cortex isolated from adult (4-6 month-old) and old (25-27 month-old) Wistar rats exposed to an object-recognition training. The paradigm consisted of 6 sessions in which the animals could explore two identical objects. Rats were divided into the following groups: trained animals: adult trained (AT) and old trained (OT); untrained animals: adult control (AC) and old control (OC).

Keywords: Synaptic plasticity, Object-recognition test, Perirhinal cortex, E-PTA, Synaptic morphometry

Computer Simulation of Telomere Dynamics and Senescence

Authors: K.B. Blagoev, E.H. Goodwin

In normal human somatic cells, telomeres become shorter with each cell cycle until their chromosome end protection function fails causing the cells to senesce. Previously telomere loss was thought to be gradual, and the approach to cellular senescence was likened to a mitotic clock in which the shortest telomere of a progenitor cell determined the maximum number of cell doublings. In addition to the basal loss, recent evidence indicates that there are occasional large gains, losses and exchanges of telomeric DNA collectively called telomere dynamics.

Keywords: modeling, telomere dynamics, Monte Carlo , ,

Telomeres and human disease: a matter of bad ends

Authors: M.A. Blasco
Audio: (Audio)

Telomeres are chromosome end-capping structures, which protect the chromosome ends from unscheduled DNA repair and degradation. Telomeres are composed of repetitive DNA (TTAGGG repeats) bound to an array of specialized proteins. The length of telomere repeats and the integrity of telomere-binding proteins are both important for telomere protection. In addition, telomeres are regulated by a number of epigenetic modifications, thus pointing to a higher-order control of telomere length and function.

Keywords: telomeres, stem cells, cancer, aging, TRF2

Current and Future Stategies for the Treatment of Metabolic Storage Disorders

Authors: R.O. Brady
Audio: (Audio) (Slides)

Following the unprecedented success of enzyme replacement therapy (ERT) in patients with Type 1 (non-neuronopathic) Gaucher disease, this therapeutic approach has been applied to a number of other hereditary metabolic storage disorders of humans. I shall discuss the responses to ERT in patients with Fabry disease, Hurler disease, Maroteaux-Lamy disease and Pompe disease. Because impairment of the central nervous system does not improve with ERT alone, additional therapeutic modalities have been initiated to treat patients with brain involvement.

Keywords: Enzyme replacement, substrate reduction, chaperone , ,

From disease-oriented to aging/longevity-oriented studies

Authors: A. Budovsky, K. Muradian, V. Fraifeld

Aging should be considered a major risk factor for life-threatening degenerative pathologies including atherosclerosis, cancer, neurodegenerative diseases, diabetes type II, osteoporosis, and sarcopenia. Although an apparent paradox, it appears that the most effective way to delay or even to avert the age-related pathology is to live longer. This is definitely exemplified by the phenomena of negligible senescence observed in certain species, exceptional longevity in humans, and by different experimental models of extended life span.

Keywords: Aging, diseases, epigenetics, lifespan extension,

Mitochondrial genome anatomy and species-specific lifespan

Authors: G. Lehmann, A. Budovsky, K. Muradian, V. Fraifeld

Several lines of evidence implicate mtDNA in the control of aging and longevity. Yet, there is a limited number of studies attempting to compare the basic mtDNA characteristics with species-specific (maximum) lifespan (MLS). Therefore, we examined correlative links between mtDNA composition and MLS of multicellular eukaryotes. For this purpose, we built a new database containing 144 species from 11 classes.

Keywords: mtDNA, maximum lifespan , , ,

Memory B-cell subpopulations in aged

Authors: G. Colonna-Romano, M. Bulati, A. Aquino, S. Vitello, G. Clesi, C. Caruso

The literature on immunosenescence has focused mainly on the roles of T cells in the induction of the immune response and in the generation of the immunological memory. On the other hand, little is known about the B cell memory. According to the expression of sIgD and CD27 as markers for B memory cells (1), we have studied nave and memory B lymphocytes in our aged population. Our data show a decrease of nave IgD+CD27- B cells and a slight (not statistically significant) increase of memory IgD-CD27+ B cells.

Keywords: Ageing, CD27, IgD, B memory ,

Poly(ADP-ribosyl)ation capacity of human T lymphocytes in vitro and in vivo as a function of age

Authors: Kathryn Annett [1], Alexander Bürkle [2], Muriel Malaisé [2], Orla Duggan [1], Robin Freeburn [1], Paul Hyland [3], Christopher Barnett [3], Anders Wikby [4], Graham Pawelec [5], Yvonne Barnett [1,3]
Audio: (Audio)

Poly(ADP-ribosyl)ation is an immediate response to DNA damage. This post translational modification of nuclear proteins is mostly catalysed by poly(ADP-ribose) polymerase-1 (PARP-1), and has been implicated in several crucial cellular processes including DNA repair, recombination and genomic stability.

Keywords: ageing, immunosenescence, T cells, poly(ADP-ribosyl)ation, PARP-1

Cellular senescence, cancer and aging

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

Normal cells respond to DNA damage, dysfunctional telomeres and other potentially oncogenic events by entering an essentially irreversible state of arrested growth and altered function termed senescence. The senescence response, like the apoptotic response, is an important tumor suppressive mechanism for mammals. In addition, there is increasing evidence that the senescence response may be an example of evolutionary antagonistic pleiotropy and contribute to aging.

Keywords: , , , ,

Association between the HLA-A2 allele and Alzheimer disease

Authors: F. Listì, G. Candore, C.R. Balistreri, S. Vasto, M.P. Grimaldi, G. Colonna-Romano, A. Giacalone, V. Orlando, D. Lio, C. Franceschi, C. Caruso

The progressive neurodegenerative inflammatory age-related disease, Alzheimers disease (AD), is the most common cause of dementia in the elderly. Several factors, genetic and environmental, are involved in the onset of AD. Epidemiological data suggest that some genetic determinants of AD might reside in those polymorphisms for the immune system genes that regulate immune inflammatory responses, such as the Major Histocompatibility Complex (MHC). Therefore, MHC polymorphisms have been the focus of a large number of AD association studies.

Keywords: AD, HLA, immune response, ,

Biology of longevity: role of the immune system

Authors: G. Colonna-Romano, G. Candore, A. Aquino, M. Bulati, S. Vitello, D. Lio, I.M. Rea, C. Caruso
Audio: (Audio) (Slides)

Ageing is an inexorable intrinsic process that affects all cells, tissues, organs and organisms. In fact, humans, as well as the other animals, are designed as a compromise to guarantee optimal survival until the time of reproduction based on natural selection that is effective until that age, so the post-reproductive physiology of an organism (i.e., ageing) is an epigenetic and pleiotropic manifestation of the optimisation for early fitness.

Keywords: Centenarians, Immunogenetics, Immune Response, Inflammation, Longevity

Tissue-specific effect of age and caloric restriction diet on mitochondrial DNA content

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

The decay of mitochondrial function is considered one among the major contributors of the age-related degenerative processes. Caloric restriction (CR) diet is widely known as the only treatment able to delay aging, increasing both the mean and maximum lifespan in a wide phylogenic range of animals including rodents and non human primates. Several evidences show that CR diet is able to prevent or reduce the age-dependent accumulation of oxidative damages to mitochondrial DNA (mtDNA) in different rodent tissues, mainly reducing the OH8dG content and the number of mtDNA deleted species.

Keywords: caloric restriction diet, aging, mitochondrial DNA content, Real Time PCR ,

Parthenogenetic Embryonic Stem Cells in Primates

Authors: J.B. Cibelli
Audio: (Audio)

Mammalian parthenogenetic or androgenetic embryos, when transferred into the uterus of a recipient animal, cannot develop to term. This lack of developmental competence is attributed to imprinted genes, expressed only if contributed by the mother or by the father.

Keywords: Parthenogenesis, embryonic stem cells, primate, imprinting ,

The decay of extra-cellular matrix proteins; an inevitable consequence of old age?

Authors: M.J. Collins, S. Ritz-Timme
Audio: (Audio) (Slides)

Our twin research groups (Collins, York; Ritz-Timme Düsseldorf) focus on the recovery of proteins from aged remains; often very aged remains - from forensic and archaeological samples. Our peculiar focus on the persistence and decay of proteins in these old samples has given us particular insights into the key degradation reactions which occur to proteins post-synthesis.

Keywords: Collagen, Elastin, Osteocalcin, Racemization, Forensic Medicine

Understanding and reversing aging of muscle precursor cells

Authors: I.M. Conboy
Audio: (Audio)

Molecular regulation of muscle repair recapitulates the mechanisms operating in embryonic organogenesis. Namely, the evolutionary conserved Notch and Wingless (Wnt) molecular pathways regulate the cell-fate determination of the stem and progenitor cells in adult skeletal muscle regenerating after injury. Recent data strongly suggest that the decline in regeneration-specific signaling and deteriorated regenerative potential are not irreversible signatures of stem-cell aging.

Keywords: , , , ,

Ex vivo gene delivery of NGF in Alzheimer's Disease

Authors: M.H. Tuszynski, J.M. Conner
Audio: (Audio)

In animals, Nerve Growth Factor (NGF) stimulates cholinergic neuronal function, improves learning and memory, and prevents cholinergic degeneration caused by injury or aging. NGF may therefore ameliorate cholinergic cell loss and reduce cognitive decline in Alzheimer's disease (AD). Using ex vivo gene delivery primary autologous fibroblasts from eight early-stage Probable AD patients were genetically modified to produce and secrete human NGF.

Keywords: NGF, cholinergic, gene therapy, cllinical trial, basal forebrain

Membership in high-risk genetic groups predicts Alzheimer's disease and age-at-onset

Authors: E.H. Corder, R. Huang, H.M. Cathcart, I.S. Lanham, G.R. Parker, D. Cheng, S.E. Poduslo
Audio: (Audio) (Slides)

Neurodegeneration is a brickwall when considering extreme longevity. Alzheimer’s brain changes, i.e. the accumulation of neurofibrillary tangles and senile plaque, can begin in early adulthood and are almost universal by age 80. The continued loss of pyramidal neurons in early-affected brain areas, i.e. the hippocampus, and the sequential regional brain spreading of lesions predicts that eventually there will be compromised cognition.

Keywords: , , , ,

The neurosecretory system is hypertrophied in senescence-accelerated mice

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

The neurosecretory system (NSS) of the hypothalamus acts as a pivotal area that regulates important endocrine functions. The NSS has been studied from different points of view and its anatomical, cellular, and electrophysiological features have become important areas of research. Furthermore, the NSS has been related to some ageing processes in which its activity could play an important role in regulating the overall-ageing process. The NSS is formed by the paraventricular and supraoptic nuclei whose neurons synthesize the neurohormones oxytocin and arginine-vasopressin.

Keywords: ageing, neurohormones, senescence-accelerated mouse, hypothalamus ,

Analysis of HLA-DQA, HLA-DQB frequencies in a group of Sardinian centenarians

Authors: A. Crivello, D. Lio, G. Candore, G.I. Forte, L. Scola, G. Colonna-Romano, M.G. Pes, C. Carru, L. Ferrucci, L. Deiana, G. Baggio, C. Franceschi, C. Caruso

Some studies suggest that genetic determinants of longevity might reside in the polymorphisms for genes that regulate immune responses as HLA genes. Some HLA alleles or haplotypes that confer resistance to infectious disease respectively via peptide presentation or via antigen non specific stimulation, have been selected all through evolution. Some of the highly conserved haplotypes are composed by the HLA-DRDQ alleles and in some instances HLA-DQ alleles play a central role in the association to disease.

Keywords: HLA, longevity, Sardinia, centenarians,

Reactivating chaperone-mediated autophagy: the advantages of preserving a selective autophagy

Authors: A.M. Cuervo
Audio: (Audio) (Slides)

We have previously identified a decrease with age in the activity of a lysosomal pathway involved in the selective degradation of soluble cytosolic proteins in most types of mammalian cells. This autophagic pathway, known as chaperone-mediated autophagy (CMA), is preferentially activated under stress conditions such as nutritional stress or exposure to different toxic derivatives. Under these conditions, an amino acid motif in the substrate proteins is recognized by a cytosolic chaperone complex, which targets the substrate to the lysosomal membrane.

Keywords: autophagy, lysosomes, oxidation, chaperones, proteolysis

Tripterine inhibits the expression of adhesion molecules in activated endothelial cells

Authors: Deng-hai Zhang [1,2], Anthony Marconi, Li-Min Xu, Chun-xin Yang [3], Guo-wu Sun [4], Xiao-ling Feng [4], Shu-min Xu [2], Chang-quan Ling [5], Wan-zhang Qin [3], Georges Uzan [1], Patrizia d'Alessio [1]

Introduction: Chemical compounds derived from plants used in traditional medicine to cure disease, are an important source for the development of new active pharmaceutical molecules. Using such a strategy, tripterine, a triterpenoid from the Celastrae family, extracted from the Chinese herbal plant Tripterygium wilfordii Hook F (TWHF) (Chou and Mei, 1936), has attracted much interest (Calixto et al, 2004).

Keywords: , , , ,

WILT: still crazy after both these years?

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

Two years ago, at the first SENS conference (IABG 10), I presented a decidedly ambitious proposal for combating cancer much more thoroughly than can realistically be expected from any therapy currently existing or under development.

Keywords: WILT, cancer, telomerase, ALT, gene targeting

Interspecies SCNT with ES cell mito-rescue: a proposed solution to some key ethical and logistical problems

Authors: A.D.N.J. de Grey

Despite impressive advances, adult stem cells remain less promising than embryonic stem (ES) cells for treatment of numerous human conditions, including age-related ones. The pace of ES cell research has, however, been slowed by three critical difficulties. First, the embryo from which the ES cells are derived will not be totally immunocompatible with the recipient (even if HLA alleles are matched).

Keywords: WILT, SCNT, mitochondrial DNA, mitochondrial biogenesis, oocyte availability

SMK-1, an essential regulator of DAF-16/FOXO3a mediated longevity

Authors: H. Ma, S. Wolff, D. Burch, G. Maciel, P.J. Woodring, T. Hunter, A. Dillin
Audio: (Audio)

Insulin/IGF-1 signaling (IIS) regulates the aging process in worms, flies and mice. In the nematode Caenorhabditis elegans, IIS regulates processes in addition to aging such as early developmental decisions and the reproductive status of the animal. We present evidence for the placement of the uncharacterized gene, smk-1, within the insulin/IGF-1 pathway. Genetic analysis indicates that loss of smk-1 specifically influences the aging related function of the DAF-2 (IIS) signaling pathway.

Keywords: insulin/IGF-1, C. elegans, longevity, FOXO3a, DAF-16

Antibody quality in old age

Authors: D.K. Dunn-Walters
Audio: (Audio)

There is very little change in the quantity of antibodies produced, of any isotype, with age. There is, however, a change in the quality of the antibody response. Older people produce less antibodies that are specific for the activating pathogen or vaccine. At the same time, the number of non-specific antibodies increases. Quite often these antibodies have self reactivity (such as anti-dsDNA). The appearance of these antibodies is not associated with pathogenic autoimmune disease, although it is true that the incidence of some autoimmune diseases increases with age.

Keywords: immunity, antibody, affinity maturation, ,

Cryopreservation of Complex Living Systems: The Missing Link in the Regenerative Medicine Supply Chain

Authors: G.M. Fahy

The current research effort in regenerative medicine has involved the expenditure of several billion US dollars to date, but relatively little attention has been paid to the fate of engineered tissue replacements between the time they are produced and the time they are used (inventory control and supply chain management). The problems of cryogenic banking of complex tissue replacements are much more serious than those involved in ordinary cell and tissue banking, and new technology will be required to overcome the limitations of current methods.

Keywords: cryopreservation, transplantation, life extension, vitrification, freezing

Transfection of CCE embryonic stem cells with EGFP and BDNF genes by electroporation method

Authors: F. Fathi, T. Altiraihi, J. Mowla, M. Movahedin

Unlimited self renewal and potential capacity of embryonic stem cells (ESC) in differentiating into a wide variety of cell types has made the cells an attractive source of donor cells for developmental studies and cell therapy. Blocking the differentiation of ES cells in culture and using them in clinical applications requires some genetic manipulations of the cells. The aim of the present study is to transfect CCE ES cells by EGFP and BDNF Genes. For this purpose pIRES2-EGFP and pcDNA3-hBDNF-v5 plasmids were used.

Keywords: Embryonic Stem Cells, Transfection, Electroporation, GFP, BDNF

Glucosepane Crosslink Breakers: Necessity and Prospects

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

Extracellular aging -- accumulating molecular damage by glycation, oxidation, and crosslinking of long-lived extracellular proteins, mainly collagen and elastin -- is a major cause of several important human aging pathologies. Crosslinking increases mechanical stiffness of blood vessels and urinary bladder. Crosslinking impairs functioning of kidney, heart, retina, and other tissues and organs. Glycation adducts trigger inflammatory signaling, provoking tissue damage and cancers. Crosslinking tightens up the extracellular matrix (ECM), hardening it against natural turnover processes.

Keywords: crosslinks, extracellular, glucosepane, collagen, turnover

Historical dynamics of natural death rate of the population and variations of atmospheric radiocarbon

Authors: A.A. Germanskaia

The retrospective research of death rate of the population of some Western Europe countries -Norway, Denmark, Sweden, Germany - FRG, France, Switzerland, Great Britain, Belgium-, as well as of the USA and Australia, considering the periods of 19-th and 20-th centuries was carried out. The choice of the countries and historical depth of research of the population death rate were generally conditioned by the presence of national demographic statistical databases of necessary volume and quality.

Keywords: the radioactive carbon, natural death rate, , ,

Radiocarbon ageing mechanism

Authors: A.M. Germansky, A.A. Germanskaia

The fluctuations of natural death rate of the population corresponding with the variations of carbon - 14С concentration in the atmosphere were found out. Considering this point, and also taking into account the already known peculiarities of 14С radiating biological functioning, the hypothetical mechanism of radiocarbon influence on a person's ageing rate was offered.

Keywords: the radioactive carbon, natural death rate, DNA, ,

Natural death rate variations of the Earth population and radiocarbon ageing mechanism

Authors: A.M. Germansky

In the work the tables describing death rate of the population of 48 European countries during the period between 1970 and 2000 years as well as the death rate statistics related to the population of 191 countries for 1999th, 2000th and 2001st years were used.

Keywords: the radioactive carbon, natural death rate, ДНК , ,

Telomere Dynamics and Cell Proliferation

Authors: E.H. Goodwin, S.M. Bailey, C.K. Sanders, and K.B. Blagoev
Audio: (Audio)

Telomere length changes are far more dynamic than previously thought. In addition to a gradual loss of ~100 base pairs per telomere in each cell division, large losses as well as gains may occur within a single cell cycle. How these processes, collectively referred to as telomere dynamics, influence cellular proliferation and the approach to senescence is poorly understood. We are investigating how telomere exchange, extension, and deletion affect the proliferative potential of telomerase-negative somatic cells.

Keywords: telomere, senescence, ALT , ,

Alagebrium: Intervention on the A.G.E. pathway modifies deficits caused by aging and diabetes

Authors: H.B. Haimes
Audio: (Audio) (Slides)

The accumulation of non-enzymatic advanced glycation endproducts (AGEs) in tissues and organs as a normal part of the aging process is accelerated by hyperglycemia. These AGEs provoke inflammatory, angiogenic and sclerotic cytokines that ultimately cause dysfunctional tissue pathology. AGEs also quench available nitric oxide, a potent vasodilator and are a potent stimulant for oxidative stress through generation of reactive oxidant species.

Keywords: Glycation, Heart failure, Erectile Dysfunction, diabetes ,

Can continuous regeneration lead to immortality? Studies in the MRL mouse

Authors: E. Heber-Katz
Audio: (Audio)

Studies in the MRL mouse have demonstrated a unique capacity to heal wounds through a process of regeneration. This has been shown in multiple tissue types including muscle, cartilage, and connective tissue and in organs such as the ear, heart, and digits. The concept that life extension may be mediated by regeneration and its associated processes is a reasonable proposal. We will present molecular and cellular evidence from the MRL which examines this possibility.

Keywords: , , , ,

Caloric Restriction Protects Mitochondrial Function with Aging in Skeletal and Cardiac Muscles

Authors: R.T. Hepple, D.J. Baker, M. McConkey, T. Murynka, and R. Norris
Audio: (Audio)

Aging is associated with impairment in mitochondrial function that has been implicated in tissue dysfunction particularly in post-mitotic tissues. We examine here the impact of long term caloric restriction (CR), begun in juvenile male Fischer 344 X Brown Norway F1-hybrid rats, on the age-associated decline in oxidative capacity and mitochondrial function across a range of metabolic and contractile phenotypes in skeletal muscles, and in the most highly aerobic muscle, heart.

Keywords: mitochondria, caloric restriction, mitochondrial DNA, mitochondrial biogenesis ,

Negligible Senescence - How will we know it when we see it?

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

The bold assertion by proponents of SENS (namely Aubrey de Grey) that "SENS is a practical, foreseeable approach to curing aging" has stirred considerable controversy among gerontologists. The reformulation of this assertion into a testable hypothesis will not only require concise definitions for the somewhat subjective terms "practical", "foreseeable", and "curing", it will require a precise definition of the term "aging". To facilitate proper experimental design, this definition must focus on the nature of aging itself, not its causes or consequences.

Keywords: Aging, functional capacity, biomarkers, longevity ,

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 , ,