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.

Have we reached the point for in vivo rejuvenation?

Authors: A. Abramovich, V. Fraifeld

To date, the efficacy of replacement therapy by means of autologous stem cells is hindered by at least 3 factors: (i) the lack of sufficient number of autologous stem cells; (ii) the existence of stem cells with aged-phenotype of reduced repair capacity; (iii) the reduced potential of replacement therapy to repair non- or slow-turnover tissues. Lately, groundbreaking research has shown that somatic cells may be reprogrammed to a pluripotent state by the induction of a specific set of genes in vitro – creating induced pluripotent stem cells (iPS).

Keywords: aging, cell reprogramming, induced pluripotent stem cells, rejuvenation in vivo

Use of a parasite-derived protein complex to modulate the function of mitochondria in human cells

Authors: S. Mukherjee, B. Mahata, B. Mahato, S. Adhya

Recent advances have highlighted the crucial role played by mitochondria in the etiology of a variety of rare maternally inherited disorders, in common complex diseases, as well as in normal physiological processes such as aging. One approach to the management of mitochondrial diseases would be to develop reagents to modulate mitochondrial function in vivo. Work in our laboratory is focused on the characterization of a multi-protein complex (the RNA Import Complex or RIC) from the kinetoplastid protozoon Leishmania tropica that transports tRNAs across mitochondrial membranes.

Keywords: mitochondria, RNA delivery, protein complex

Retarding immune senescence and reducing infections in ageing

Authors: A. Akbar

Human memory T cell pools proliferate and differentiate at varying rates that are determined by the frequency of lifelong antigenic re-encounter with different specific antigens. An important question is whether certain specific pools of memory T cells may be driven to exhaustion in elderly subjects, a pertinent point in view of the increasing human life expectancy. An emerging consensus is that cytomegalovirus (CMV), a b-herpesvirus with a prevalence of 60-90% worldwide, is an agent that induces specific T cells to extreme differentiation.

Microbial degradation of 7-ketocholesterol

Authors: P.J. Alvarez, J.M. Mathieu

Medical bioremediation is the proposed approach of augmenting human catabolic machinery with microbial enzymes in order to prevent the accumulation of deleterious intracellular substances associated with increasing age. It has been hypothesized that one of the substances of interest, 7-ketocholesterol (7KC), could at least be partially responsible for the progression of atherosclerosis. Although only found in small quantities in atherosclerotic lesions, oxidized sterols nevertheless have potent biological effects that are only partly understood at this time.

Keywords: medical bioremediation, 7-ketocholesterol, atherosclerosis, LysoSENS

Hemoglobin levels influence exercise tolerance but not the benefits of exercise training in chronic heart failure patients

Authors: M. Balice Pasquinelli, V. Bogdanova, P. Cristofini, P. Sellier, M.C. Iliou

We regret that the details of this abstract are currently unavailable.

The effect of the ketogenic diet on rat brain aging

Authors: M. Balietti, B. Giorgetti, P. Fattoretti, Y. Grossi, F. Orlando, M. Solazzi, D. Platano, G. Aicardi, C. Bertoni-Freddari

Ketogenic diets (KD), successfully used in the treatment of some forms of pediatric epilepsy, have recently been tested in the therapy of other diseases, including traumatic brain injuries, hypoxia-ischemia, mitochodriopathies, and cancer. To date, little is known about their consequences on aging.

Keywords: ketogenic diet, synaptic morphology, synaptic mitochondria, hippocampus, brain aging

TLR2 and age-related diseases: potential effects of Arg753Gln and Arg677Trp polymorphisms in acute myocardial infarction

Authors: C.R. Balistreri, G. Candore, F. Listi, M.P. Grimaldi, E. Incalcaterra, M. Caruso, E. Hoffmann, G. Colonna-Romano, D. Lio, C. Caruso

Inflammation is a key mechanism in the onset of age-related diseases. Variations in genes encoding molecules involved in inflammatory responses may therefore influence the risk for age-related diseases, as atherosclerosis, possibly through interaction with chronic infections and pro-inflammatory environmental risk factors such as smoking, diabetes and obesity. The TLR2 and TLR4 genes, both involved in the inflammatory process, are potential candidates and TLR4 has been previously associated with cardiovascular disease, although other studies have failed to confirm this.

Keywords: inflammation, atherosclerosis, AMI, TLR2,

ALTernative ways to immortality. blessing or curse?

Authors: W. Berger

Cellular immortalization obtained by activation of telomere stabilisation mechanisms is believed to be essential for development of human cancer. This implies that inhibition of such mechanisms should represent an ideal strategy in cancer therapy. In most cases, tumour cells activate the telomere-elongating enzyme telomerase during malignant progression. Consequently, several experimental therapy approaches focus on targeting telomerase.

Keywords: telomere stabilisation mechanisms, lung cancer, glioblastoma, ALT, telomerase

Selective decline of the metabolic competence of oversized synaptic mitochondria in the old monkey cerebellum

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

The morphofunctional features of synaptic mitochondria positive to the activity of cytochrome oxidase (COX) were investigated in the cerebellar cortex of adult and old monkeys to seek alterations of the energy metabolism specifically occurring at the neuronal synaptic compartment with advancing age. Numeric density (Nv), volume density (Vv) as well as average volume (V) and average length (Fmax) were the mitochondrial ultrastructural parameters measured by computer-assisted morphometric methods.

Keywords: mitochondrial metabolic competence, monkey, cytochrome oxidase, megamitochondria, cerebellum

Decreased presence of perforated synapses in a triple-transgenic mouse model of Alzheimer's disease

Authors: C. Bertoni-Freddari, B. Giogetti, M. Balietti, T. Casoli, G. Di Stefano, L.M.T. Canzoniero, S. Sensi, P. Fattoretti

Transgenic mouse models of Alzheimer's disease (AD) are useful systems for understanding the genotype-phenotype interaction involved in this pathology. The innovative 3xTg-AD (APP/Tau/PS1) mouse model closely mimics the AD pathogenetic process as it develops clinically relevant pathological hallmarks, i.e. both neuritic A-beta plaques (by 6 months of age) and tangles (by 10-12 months of age).

Keywords: perforated synapses, triple-transgenic mouse, Alzheimer disease, morphometry, hippocampus

Evidence that cryonics may work

Authors: B.P. Best

Deep hypothermia can result in reversible arrest of neurological activity. The anatomical basis of mind is preserved much longer than six minutes in the absence of oxygen. Cryogenic vitrification can potentially preserve the anatomical basis of mind for many thousands of years. If future science is capable of rejuvenation, then future science should also be capable of reviving, curing and rejuvenating humans who were cryopreserved using cryonics technologies.

Keywords: cryonics, rejuvenation, vitrification, ischemia, future

A highly sensitive diagnostic assay for aggregate-related diseases e.g. prion diseases and Alzheimer's disease

Authors: E. Birkmann, S.A. Funke, F. Henke, D. Willbold, D. Riesner

In many neurodegenerative diseases e.g. Prion Diseases, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, protein aggregates are formed in the very beginning or in the progress of disease. Up to now it is not known, if these aggregates are causative or symptoms in the different diseases, but many studies show, that the aggregates or even oligomers of the according proteins are neurotoxical and therewith a reason of neurodegeneration.

Keywords: neurodegenerative diseases, diagnostic assay, aggregate-related diseases, prion diseases, Alzheimer's disease

Differentiation of radial glia cells into astrocytes is a possible ageing mechanism in mammals

Authors: O.G. Boyko

In one's time O.M. Ivanova-Kazas supposed that the senescence phenomenon can be understood only by comparison of design of primitive ageless animals with senescent forms. At comparison of ageless vertebrates forms (some fishes, tortoises, etc.) with mammals among which ageless species do not occur, it became clear that the generation of neuroblasts in adult/ embryonic phenotypes at vertebrates and the sites of their ultimate localization are disconnected.

Keywords: aging, mammals, astrocytic hypothesis, radial glial fibres,

Use of Trichinella Railliet 1895 vaccine for prevention and treatment of immune deficiencies

Authors: V. Britov, E. Nivin

Secondary immunodeficiency is widespread in developed countries. It is mostly caused by the lack in evolutionary-shaped antigenic stimulation of immunity. The marked decline in cellular immunity (which plays the main role in the structural homeostasis) results in increased autoimmune and degenerative diseases, chronic infections and cancer, and characterizes immune aging process.

Keywords: immunity, immunodeficiency, vaccine, trichinaelle,

Regulatory T cells in frail elderly

Authors: M. Bulati, G. Colonna-Romano, A. Aquino, S. Vitello, C. Ventura, D. Lio, G. Candore, C. Caruso

Age-related diseases involve a wide range of factors such as chronic antigenic stress, inflammatory status and genetic background, which affect immune system and its homeostatic mechanisms. In the last years several types of cells involved in the regulation of the immune system have been identified. It is believed that cells with regulatory functions play a central role in the control of autoimmunity and inflammation.

Keywords: T regulatory, elderly, frailty, ,

The possibilities of use of "GRINIZATION" multinutrient functional peptide complex to prevent ageing

Authors: A.V. Bulavka, N.I. Linnik, O.G. Boyko

According to modern conception maximum life span is defined by the speed and particular qualities of organism metabolism. Metabolic disturbances cause accumulation of mutation, apoptosis, shortening of telomeres, etc. on the cell level, and on the organism level they cause ageing. The use of "GRINIZATION" multinutrient functional peptide complex, which contains digestible valuable proteins, fatty acids, vitamins and minerals in recommended quantities, ensures correction of metabolic disturbances and as a result prevents organism ageing effectively.

Keywords: GRINIZATION, aging, malignant neoplasms, hepatitis,

Zinc, copper and amyloid in Alzheimer's disease

Authors: A.I. Bush

Background: The generation, aggregation, redox activity and toxicity of amyloid beta (Abeta) are modulated by neocortical transition metals (especially copper and zinc) in Alzheimer's disease (AD). Clioquinol is an 8-hydroxyquinoline that promotes matrix metalloproteinase clearance of Abeta, inhibits metal-mediated redox activity and oligomerization of Abeta, mitigating Abeta toxicity in vitro and brain Abeta accumulation in transgenic mice. Oral clioquinol also slowed cognitive decline in patients with moderately severe AD in a pilot phase 2 clinical trial.

Keywords: amyloid, Alzheimer's disease, copper, zinc, oxidation

Identification of biomarkers of human muscle aging and senescence

Authors: G. Butler-Browne, M.-C. LeBihan, A. Bigot, D. Furling, F. Svinartchouk, D. Bechet, V. Mouly

Muscle loss is the most common phenomenon of normal healthy aging and frequently leads to frailty and loss of independance in the elderly . It is important to understand the basic cellular mechanisms underlying this impairment. Decrease in muscle strength is associated with a decrease in cross sectional area of the muscle fibres, a decrease in capillary bed density as well as an increase in fibrotic tissue. A proteomic analysis is currently being carrried on biopsies of human skeletal muscle from young and old individuals in order to identify biomarkers of normal aging.

Keywords: , , , ,

Adding beneficial genes to the body with phage integrases

Authors: M.P. Calos, A. Keravala, W.E. Jung, C.L. Chavez, L.E. Woodard, J.J. Hoyt, A. Farruggio, V. Gabrovsky

Gene therapy represents a creative strategy to correct or enhance gene products that improve health and longevity. We now possess a greatly improved understanding of the human genome. This information provides many therapeutic opportunities, but new tools are needed to manipulate the genome in safe and precise ways. Over the past several years, my lab has developed a novel strategy for adding genes to mammalian genomes by using a phage integrase, derived from the phiC31 phage of Streptomyces soil bacteria.

Keywords: gene therapy, hemophilia, muscular dystrophy, integration, phage integrase

Immunosenescence and anti-immunosenescence therapies in ageing

Authors: G. Candore, S. Vasto, C.R. Balistreri, F. Listi, M.P. Grimaldi, G. Colonna-Romano, L. Scola, D. Lio, C. Caruso

Ageing is a post-maturational process that, due to a diminished homeostatic capacity and increased vulnerability, reduces responsiveness to environmental stimuli and is generally associated with an increased predisposition to illness and death. Accordingly, the incidence of infections, cancers, chronic inflammatory diseases such as atherosclerosis and Alzheimer's disease increases with age. These data suggest a key role for immunity in the survival of the elderly because susceptibility to these diseases depends at least in part on immune function.

Keywords: inflammation, immunosenescence, ageing, therapy,

Genetics of successful ageing: goals and future perspectives, a pharmacogenomics approach to prevent unsuccessful ageing

Authors: G. Candore, S. Vasto, C.R. Balistreri, F. Listi, M.P. Grimaldi, G. Colonna-Romano, L. Scola, D. Lio, C. Caruso

Several data indicate the presence of a strong familial component of longevity that is largely determined by genetics, and a number of possible associations between longevity and gene polymorphisms have been described. The study of centenarians who are the best example of successful ageing is a breakthrough strategy to get insight into the genetics of longevity. In this presentation we will discuss relevant data on longevity with particular focus on inflammation gene polymorphisms which could affect an individual's chance to reach the extreme limit of human life.

Keywords: longevity, genetics, inflammation, atherosclerosis, Alzheimer

Oxidative stress implication in acute heart failure

Authors: J.C. Charniot, N. Vignat, D. Bonnefont Rousselot, V. Bogdanova, K. Zerhouni, J.J. Monsuez, J.Y. Artigou

Aim of the study: Oxidative stress implication (OS) is more important in pathology: ischemia reperfusion sequence (acute coronary syndromes, cardiac surgery, transplantation...). In heart failure, OS implication is less known. This study aimed at evaluating OS in acute heart failure.

Method: patients consecutively hospitalized in department of cardiology with a first oedema pulmonary complicated a dilated cardiomyopathy (CMD).

Keywords: oxidative stress, oxygen free radicals, acute heart failure, cardiomyopathy, arrhythmia

Secrets of the oldest old

Authors: L.S. Coles

No abstract was filed for this talk.

Keywords: , , , ,

B cell immunosenescence in the elderly

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

The elderly suffer from an increased susceptibility to infectious disease and cancer. Aging of the immune system contribute to this state of affairs due to immunosenescence. Because repeated intermittent or chronic antigen exposure may lead to lymphocytes clonal exhaustion, chronic antigenic stress plays an important role in the compromised immunity of the elderly, who have accumulated a lifetime's exposure to infectious agents, autoantigens and cancer antigens. Literature on immunosenescence has focused mainly on T cell impairment, but B cell compartment is also affected.

Keywords: B lymphocytes, elderly, memory , ,

Stem cells dividing, sister chromatids choose fate: old stays, young moves on

Authors: M.J. Conboy, A.O. Karasov, T.A. Rando

Before cells divide, they duplicate macromolecules and organelles. When they divide, sometimes they sort the older versus newer "parts" to the daughter cells. Over 35 years ago Cairns proposed the "Immortal DNA Strand hypothesis", where the stem daughter cell might retain the older or more "original" strands of DNA and thus limit accumulating errors of replication, while continuing to proliferate for the life of an organism.

Keywords: immortal DNA, stem cell template, , ,

Inherited susceptibility for Alzheimer's disease and estimation of risk for individuals

Authors: E.H. Corder, S.E. Poduslo, F. Licastro, D.J. Lehmann, J.A. Prince

Age-related disorders such as Alzheimer's disease (AD) typically run in families, but it has proved difficult to identify the underlying genetic factors of importance even when plausible candidate genes have been identified. The type 4 allele for apolipoprotein E (APOE) is an established as a risk factor for AD, but it is neither necessary nor sufficient to predict AD. Since 1993 when APOE4 was identified a litany of candidate gene variants and environmental factors have been investigated but none convincingly identified via replication in independent samples.

Keywords: Alzheimer's disease, APOE E4, grade-of-membership analysis, genetic risk factors, estimation of risk for individuals

Allotopic mRNA localization to the mitochondrial surface: a tool for rescuing respiration deficiencies

Authors: S. Ellouze, C. Bonnet, S. Augustin, V. Kaltimbacher, V. Forster, M. Simonutti, J-A. Sahel, M. Corral-Debrinski

The prevalence of mitochondrial diseases is at least one in 5000, making them probably the most common form of metabolic disorders. There is currently no effective disease-modifying treatment for patients with mitochondrial disorders. Therefore, the disease course is generally relentlessly progressive, possibly leading to severe disability and death. The main limitation encoutered in the evaluation of gene therapies for treating or curing mitochondrial disorders is the absence of animals models reproducing their major features.

Keywords: allotopic expression, mitochondrial diseases, LHON disease, retinal ganglion cells ,

Genes of metallothioneins and inflammatory profile as possible biomarkers of ageing: comparison with atherosclerosis

Authors: L. Costarelli, E. Muti, R. Giacconi, C. Cipriano, M. Malavolta, D. Sartini, M. Emanuelli, E. Mocchegiani

Atherosclerosis is the main pathology present in elderly people leading often to the appearance of classical cardiovascular diseases with subsequent death of the subject. The etiopathogenesis of the disease is heterogeneous and the inflammatory status and the oxidative stress play the major role. In this context, pro-inflammatory cytokines (TNF-alpha) and their receptors and some proteins named Metallothioneins (MT) seem the more involved.

Keywords: metallothioneins, inflammation, microarray, atherosclerosis, ageing

Role of environmental and genetic factor interaction in the aging related disease development: the gastric cancer paradigm

Authors: A. Crivello, C. Cala, L. Scola, G.I. Forte, A.A. Gullo, L. Marasa, A. Giacalone, C. Caruso, C. Bonura, A. Giammanco, D. Lio

Association of Helicobacter pylori infection with gastric cancer is well known and might be considered a paradigmatic example of the role that interaction among environmental factors and the individual background might play in inducing age associated disease. The infection has a high morbidity rate, but a low mortality rate and is curable with antibiotic therapy. But if the infection is not eradicated become the most common cause of chronic gastritis, evolving in peptic ulcer disease and gastric cancer.

Keywords: gastric cancer, inflammation, cytokine polymorphisms, H. pylori, aging

From a newly discovered innate anticancer immune response in mice to a new treatment for human cancers

Authors: Z. Cui, I. Molnar, M.C. Willingham, G.J. Pomper, J.R. Stehle, M. Blanks

While most of the research attention has been focused on the question, why cancer occurs in about 25% of humans, a less frequently asked question has been why the other 75% of humans do not get cancer. Cigarette-smoking is a highly reliable way for humans to expose themselves to known carcinogens, causing a 100-fold increase of lung cancer rates from 0.08% in the general population to 8% in smokers. Why do the other 92% of smokers not get cancer? It has long been speculated that there is a cancer surveillance system in humans.

Keywords: cancer, cancer-resistance, cancer therapy, innate immunity, granulocytes

AISA ("Anti-Inflammatory Senescence Actives") 5203-L molecule to promote healthy aging and prolongation of lifespan

Authors: J.F. Bisson, C. Menut, M. Moutet, P. d'Alessio

In understanding the aging process three principles appear to play a principal role : metabolic control, resistance to stress and genetic stability. Longevity would be repeatedly found coupled with resistance to stress. Stress has always been considered as the sum of physical and mental responses to an unacceptable disparity between real or imagined personal experience and personal expectations. Mental responses to stress include adaptive stress, anxiety, and depression.

Keywords: stress, senescence, inflammation, plant-derived actives ,

Stem cell fusion and aging

Authors: L. Dao, A. Stolzing

This project outlines strategies for using fusion in rejuvenation therapy and presents data from initial studies on modulating fusion frequency. The capacity of adult stem cell to assist with the regeneration of tissue and organs seems to decline during aging. One way on which adult progenitor cells contribute to regeneration of tissue is by initiating and participating in fusion events.

Keywords: mesenchymal stem cells, aging, fusion, regeneration ,

Might the biogerontological impact of non-specific nDNA damage be slight?

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

Since Szilard's seminal 1959 article, the role of accumulating nuclear DNA (nDNA) damage - whether as mutations, i.e. changes to sequence, or as epimutations, i.e. adventitious but persistent alterations to methylation and other decorations of nDNA and histones - has been widely touted as likely to contribute substantially to the aging process throughout the animal kingdom. Such damage certainly accumulates with age and is central to one of the most prevalent age-related causes of death in mammals, namely cancer.

Keywords: cancer, nuclear mutations, aging, pleiotropy,

The Well Breast Massage Study

Authors: C.B. Diel

The Well-Breast Massage Study is intended to be a long-range study of the effects of breast massage and self-care on breast health. The participants of the study are a non-randomized sample of women all over the world of all ages, ethnicities, and health backgrounds. The principal investigator of the study is Caryn Boyd Diel, the Director of White Cloud Institute in Santa Fe, a school and research center for Energy Medicine and Taoist studies and Chinese self-healing techniques such as Chi Gong and Chi Nei Tsang, Asian Body therapy.

Keywords: Well Breast Massage Research Study, , , ,

Fullerene-based nanotechnology: Developing strategies to study and treat oxidative stress in aging

Authors: L.L. Dugan

A number of genes and molecular pathways have been linked to the aging process in lower organisms such as fruit flies, worms, and mammals. Common among these observations is the idea that oxidative stress and altered handling of reactive oxygen species (ROS) may be critical components of aging. Reactive oxygen species (ROS), generated by normal metabolism of oxygen in cells, are clearly important for normal cellular function and physiology, but can also be toxic, a two-faced ÒJanusÓ of cell biology.

Keywords: , , , ,

Accelerated protein aggregation and amyloid fibril formation of the prion protein in the presence of glycogen

Authors: C. Dumpitak, G. Panza, J. Stohr, E. Birkmann, D. Riesner

Among protein misfolding diseases the transmissible spongiform encephalopathies like Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle or scrapie in sheep and goats, are unique neurodegenerative diseases: They can be of either sporadic, or genetic, or infectious origin. Independent of the underlying etiology they are always infectious. The infectious agents are composed primarily of a host protein, the so-called prion protein (PrP).

Keywords: protein misfolding, amyloid, prion, glycogen, corpora amylacea

Using nanotechnology to repair the body

Authors: R.G. Ellis-Behnke, Y.X. Liang, D.K.C. Tay, G.E, Schneider, K.F. So

The intersection of nanotechnology and medicine is here. While nano biomedicine has led to wildly futuristic promises, it has also presented real breakthroughs in drug research, development and formulation. Two significant nanobiomedical advances will be discussed, each with the potential for great promise in treating human conditions in the very near future.

Keywords: CNS regeneration, hemostasis, tissue repair, functional return of vision, nanomedicine

Stimulating neurogenesis in "non-neurogenic" brain regions

Authors: J.G. Emsley

Contrary to previously held beliefs about the static nature of the adult mammalian brain, it is in fact capable of generating new neurons that can integrate into its complex circuitry. The recent development of new techniques has resulted in an explosion of research demonstrating that neurogenesis, the birth of new neurons, constitutively occurs in two specific regions of the adult mammalian brain (olfactory bulb and hippocampal dentate gyrus), and that there are significant numbers of multipotent neural precursors, or "stem cells," in many parts of the adult brain.

Keywords: cortex, development, neural precursors, neurogenesis, stem cells

Inteins and allotopic expression of mtDNA encoded proteins

Authors: J.A. Enriquez

Expression of the 13 mtDNA-encoded proteins from nuclear transgenes (allotopic expression) might be the most effective gene-therapy strategy. However, there is an important difficulty, the extreme hydrophobicity of these proteins, which prevents their import into mitochondria from the cytosol.

The use of inteins (1), self-splicing "protein introns", might solve this problem: their insertion into such transgenes could greatly reduce the encoded proteins hydrophobicity, thus enabling import. The post-import spliced product would become the mature protein.

Keywords: , , , ,

Angiogenesis in vitro: vascular tube formation from the differentiation of murine embryonic stem cells

Authors: F. Fathi, A. Jafari Kermani, L. Pirmoradi, S.J. Mowla, T. Asahara

Introduction: In this investigation murine embryonic stem (ES) cells were used to study endothelial cell development.

Materials & Methods: Murine ES cells (CCE cell line) exposed to Alpha-MEM medium containing 10% FBS for 4 days and then cultured in endothelial basal-2 medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), and epidermal growth factor (EGF) and 5% FBS.

Keywords: embryonic stem cells, endothelial cells, tube formation, differentiation ,

Moderate physical exercise can positively modulate synaptic morphology in aging mice

Authors: P. Fattoretti, B. Giorgetti, M. Balietti, M. Solazzi, M. Malatesta, C. Zancanaro, R. Mariotti, C. Bertoni-Freddari

Current literature reports that physical exercise confers health protective benefits for both cardiovascular disease and atherosclerosis, as well as several neurological pathologies including Alzheimer's and Parkinson's diseases. However, the salutary effect of physical exercise on neuronal function remains elusive in its underlying mechanisms. In this work we sought for possible structural changes induced by moderate physical exercise (MPE) in the aging brain. Adult (12 months of age), old (27 months of age) and old-MPE (27 months of age) mice were used.

Keywords: physical exercise, synaptic morphology, synaptic plasticity, hormesis, oxidative stress

Mitochondrial dynamics in distal dendrites of hippocampal CA1 neurons of aged rats correlates with good performance in passive avoidance test

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

A progressive decline of the mitochondrial metabolic competence is associated with aging. In the brain, this phenomenon particularly affects high energy-requiring processes that take place during neuronal stimulation. Aim of the present work was to verify whether activity-dependent changes in mitochondrial parameters in distal dendrites of CA1 hippocampal neurons of aged (26-27 month old) female Wistar rats might correlate with performance differences in the passive inhibitory avoidance task.

Keywords: mitochondrial morphology, mitochondrial structural dynamics, successful aging, hippocampus, inhibitory avoidance

The metabolic syndrome: IL-10 polymorphisms influence on serological and haematological parameters in type 2 diabetes

Authors: G.I. Forte, A. Crivello, L. Scola, A. Giacalone, G. Candore, R. Testa, C. Caruso, C. Franceschi, D. Lio

Previous studies have demonstrated that genetic regulation of IL-10 production might be implied in determining the complex phenotypes of successful or unsuccessful ageing and longevity. Recently it has been reported that low IL-10 serum levels are associated to an increased susceptibility for metabolic syndrome and type 2 diabetes mellitus. As well known IL-10 secretion ability is tightly controlled at the transcription level and it seemed tempting to investigate if polymorphisms in the IL-10 gene promoter contribute to type 2 diabetes mellitus.

Keywords: metabolic syndrome, laboratory parameters, IL10 polymorphisms, unsuccessful ageing,

Common gene signature of longevity and age-related diseases

Authors: A. Budovsky, A. Abramovich, H. Yanai, V. Fraifeld

We constructed the Human Longevity Network (HLN) and the networks for the major age-related degenerative diseases (ARDs) including atherosclerosis, cancer, Altzheimer's disease, and diabetes type II, based on protein-protein interactions. There is a remarkable overlap between the HLN and the ARD networks, suggesting that common pathways stand behind both aging and age-related pathology. The common genes are highly evolutionary conserved and fall into three main categories: signal transduction, DNA maintenance and repair, and protein and energy metabolism.

Keywords: aging, age-related diseases, common gene signature, longevity, protein-protein interaction networks

The relationship between calorie restriction and the biological clock: lessons from long-lived transgenic mice

Authors: O. Froy, N. Chapnik, R. Miskin

The master clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain regulates circadian rhythms in mammals. Similar circadian oscillators have been found in peripheral tissues, such as the liver, intestine, and retina. Life span has been previously linked independently to both circadian rhythms and caloric restriction (CR). The mechanisms by which CR attenuates ageing and extends life span are virtually unknown.

Keywords: ageing, biological clock, food, caloric restriction ,

An ultra-sensitive assay for early diagnosis of Alzheimer's disease

Authors: S.A. Funke, E. Birkmann, F. Henke, D. Riesner, D. Willbold

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia, affecting more than 20 million people worldwide. Today, AD can be diagnosed with certainty only post mortem, detecting insoluble beta-amyloid peptide (Abeta) aggregates and neurofibrillary tangles in the patient's brain tissue.

Keywords: Alzheimer's disease, amyloid-beta, aggregates, early diagnosis ,

2007 network model of biological interactions causing human aging

Authors: J.D. Furber, S.A. Racunas, P. Langley

The many observable signs 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 age-related changes and with the hypothesized causes reveals several parallel cascades of events that involve multiple interactions and feedback loops. We have constructed a network diagram to aid in visualizing the many processes and interactions among them, including promising intervention points for therapy development.

Keywords: aging, network model, causes, ,

Engineering a blastema: steps toward regenerating a limb

Authors: D.M. Gardiner, A. Satoh, D. Ferris, G. Graham, S.V. Bryant, E. Rugg

Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues and organs perfectly. Given the conservation of genetic mechanisms among vertebrates, it is likely that the cellular and molecular processes that regulate urodele limb regeneration are shared among all vertebrates. It follows that since we all developed limbs as embryos, we possess the genetic program for re-making a limb (or any other organ) via these regenerative processes.

Keywords: salamander, limb, regeneration, dedifferentiation, blastema

A novel Zip2 Gln/Arg/Leu codon 2 polymorphism as risk factor for carotid artery disease in elderly

Authors: R. Giacconi, E. Muti, E. Mariani, M. Malavolta, S. Pierpaoli, C. Cipriano, L. Costarelli, S. Tesei, F. Piacenza, V. Saba, G. Boccoli, E. Mocchegiani

An impaired zinc status associated with increased pro-inflammatory cytokine production are suggested as a risk factor for carotid stenosis (CS) development. Zinc protects from atherogenesis counterbalancing the oxidative stress and preserving the integrity of the endothelial cells during inflammation. In mammals, zinc uptake appears to be mediated by members of the Zrt/Irt-like protein (ZIP) superfamily of metal ion transporters.

Keywords: Zip2, inflammation, carotid stenosis, elderly ,

Carbonylation and other modifications of histones: possible roles of epigenetics in aging

Authors: S. Goto, R. Sharma, K. Kawakam, R. Takahashi, A. Nakamura

Intra- and extra-cellular proteins are subjected to numerous forms of post-translational modifications. While most of them are physiological as in phosphorylation and glycosylation, some of them are unphysiological and potentially harmful as in oxidation and glycation. Biological aging is defined as physiological decline with time that is likely caused by alteration of proteins. Altered proteins are mostly generated by post-translational modifications.

Keywords: aging, histone, carbonylation, acetylation, dietary restriction