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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.

SRF Education: Training Future SENS Researchers

Authors: Chin G.

One of the major focuses of SRF Education is training new biomedical scientists in the SENS damage repair approach to studying the diseases and disabilities of aging. Through a collaboration with several top research institutions in the world, SRF Education has expanded its support of summer interns from seven last year to twelve this year. SRF-funded interns, both old and new, have proven to be very productive members of the SENS community.

Keywords: SENS, internships, education, aging, damage repair

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

Induction of morphological restoration of senescent

Authors: H. Choi, J.H. Rhim, S.J. Lee, K.A. Cho, S.C. Park

The Arg-Gly-Asp (RGD) peptide sequence is the cell attachment site of a large number of adhesive extracellular matrix as well as blood cells, and nearly half of the over 20 known integrins recognize this sequence. The biological effect of this peptide has been well studied for its influences on migration, growth and morphological changes especially concerning its impact on cancer cells. But its effect on senescent cells has not been thoroughly studied. We report here a novel aspect of RGD effect on the senescent phenotype.

Keywords: HDF, Human diploid fibroblasts, Replicative senescence, RGD, Arg-Gly-Asp

Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I

Authors: Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cochemé HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS, Murphy MP.

Oxidative damage from elevated production of reactive oxygen species (ROS) contributes to ischemia-reperfusion injury in myocardial infarction and stroke. The mechanism by which the increase in ROS occurs is not known, and it is unclear how this increase can be prevented. A wide variety of nitric oxide donors and S-nitrosating agents protect the ischemic myocardium from infarction, but the responsible mechanisms are unclear.

Technologies for reading, writing & interpreting omes

Authors: Church G.

New technologies for sequencing human diplotypes, transcriptomes, immunomes, microbiomes  include Fluorescent in situ Sequencing (FISSEQ), LFR (CGI) and wearable sequencing devices (Genia).   To improve interpretation of such omes from extreme youth-span individuals and to improve precision medicine requires highly integrated and comprehensive  Environmental and Trait data (GET) and cohorts  properly consented for global sharing (PGP).

Keywords: genome, technologies

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 controversal relationship between immunosenescence and apoptosis

Authors: Ciccarelli F, De Martinis M, Ginaldi L

Programmed cell death or apoptosis is a complex process that allows cells to die in a controlled fashion, On the basis of the nature of the apoptosis-inducing stimuli, an activation-induced apoptosis and a damage-induced apoptosis can be identified. The balance between removal of damaged cells via apoptosis and proliferation of needed cells is a central process in body homeostasis and its derangement is involved in many physiopathological conditions, including ageing and immunosenescence.

Keywords: Apoptosis, Activation-induced cell ceath, Damage-induced cell death, Immunosenescence, Ageing

Caenorhabditis elegans lifespan is profoundly modulated by its diet of E. coli: What are the roles of E. coli metabolism and coenzyme Q?

Authors: Saiki R, Lunceford AL, Bixler T, Dang P, Lee W, Larsen PL, Clarke CF.

Coenzyme Qn is a fully substituted benzoquinone containing a polyisoprene tail of distinct numbers (n) of isoprene groups. Q is an essential component of respiratory electron transport and a potent lipid soluble antioxidant. Extended lifespans are observed in C. elegans clk-1 mutants with defects in Q biosynthesis. Intriguingly, mice heterozygous for a clk-1 gene disruption also show increased lifespan. C. elegans fed E. coli devoid of Q8 have a significant life span extension when compared to C. elegans fed a standard Q-replete E. coli diet.

Keywords: Coenzyme Q, Ubiquinone, Dietary restriction, Caenorhabditis elegans

Isotope-Reinforced Polyunsaturated Fatty Acids Protect Yeast Cells from Oxidative Stress

Authors: K. Hirano, V. V. Shmanai, B. N. Marbois, R. Molinari, S. Morvaridi, M. Shchepinov, C. F. Clarke

Polyunsaturated fatty acids (PUFAs) are exquisitely sensitive to autoxidation damage. The autoxidation products include peroxyl and alky radicals, and small molecule aldehydes that form cross-links to other membrane components, or diffuse to other cellular sites and damage proteins and nucleic acids. Cells protect themselves from these autoxidation products by maintaining an arsenal of enzymes designed to keep reactive oxygen species in check, as well as a defensive system of small molecule antioxidants that terminate radical chain reactions.

Keywords: Isotope Effect, Lipid Autoxidation, Coenzyme Q, Ubiquinone, Fatty Acid

Collective consequences of a very long life. The right to life extension could / should be considered a human right.

Authors: Coeurnelle D.

A longer and healthier life is enjoyed by the citizens who can benefit from it. This evolution is also positive for the whole society. It is better for the economy, for a sustainable environment, for a peaceful planet, for the level of well-being in the society.This speech gives a description of positive political, economic and sociological aspects of a world with a largely delayed senescence.The question of the moral necessity of health research funding will be discussed.

Keywords: Public funding of life extension, Collective advantages of life extension, Human rights

Collective advantages of Life Extension

Authors: D. Coeurnelle
Video: (Video)

A longer and healthier life is a good thing for individuals, but it is also positive for the whole society. This speech will give a quick description of positive political, economical and sociological aspects of a world with a largely delayed senescence: lower health costs, lower level of violence, higher level of happiness...

Keywords: , , , ,

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

Secrets of the oldest old

Authors: L.S. Coles

No abstract was filed for this talk.

Keywords: , , , ,

Combined chemical and brain stimulation induction of neurogenesis in brain injury and brain degeneration of aging.

Authors: M. Colgan, L.A. Colgan

Current science elucidates several consequences of normal metabolism within the neuron that partly determine aging damage to brain function; uncontrolled oxidation, chronic inflammation, and glycation. These consequences are influenced by several exogenous chemicals; R+ lipoic acid, acetyl-L carnitine, cytidine-diphosphate choline, N-acetyl cysteine, idebenone, docosahexaenoic acid, L carnosine, nicotine-adenine-dinucleotide hydrogen, turmeric, and salicylic acid, which may inhibit damage and facilitate neurogenesis.

Keywords: neurogenesis, fMRI, brain injury, senility, neuroimaging

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

Neuroplasticity and Connectivity in the Aging Brain

Authors: T. Collura, B. Steffert, T. Steffert

While molecular and cellular strategies have a vital place in regenerative medicine to prevent the accumulating damage of aging bodies, the most important frontier is the mind, which prevails over the physical, external boundaries that confront humans. This paper describes a technique to prolong the neurological pathways in the brain that have executive control over all body processes.

Keywords: Neurofeedback, Aging Brain, , ,

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 , ,

Aging of signal transduction in stem cells

Authors: Carlson ME, Conboy MJ, O'Connor M, Silva H, Hsu M, Conboy IM.

While the underlying reasons and molecular mechanisms of physiological aging are not identical in various adult organ systems, one common characteristic is insufficient or failed regenerative processes. This age-specific lack of tissue repair, which leads to degeneration and loss of function, is perfectly exemplified in skeletal muscle and we are attempting to understand this aging process in cellular and molecular terms.

Keywords: Muscle stem cell, Niche aging, Signal transduction

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, , ,

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

Modulating Biological Events by Biophysics: An innovative Molecular Methodology using Ion Cyclotron Resonance.

Authors: Corbellini E, Corbellini M, Licciardello O, Marotta F

It has been known since long time that electromagnetic fields characterized by extremely low frequency (ELF) and intensity are able to trigger Molecular Cyclotronic Ion Resonance phenomena. However, only in the last decades, biophysical studies have shown that Molecular Cyclotronic Ion Resonance, thanks to the ELF waves, activates some fundamental elements (proteins, vitamins, mineral salts..) and makes them enter more easily through the cellular membrane thus guiding all the biochemical reactions essential for the normal cellular activity.

Keywords: Ion Cyclotronic Resonance , extremely low frequency magnetic field , Quantum Electrodynamics Coherence

Low risk for coronary artery disease and findings in the TERC region on 3q26

Authors: Corder EH

The TERC region on chromosome 3q26 was investigated for British coronary artery disease patients (n=1487) and for UK blood service donors (n=1430). The aim was to identify region-wide patterns associated with telomere length and their prevalence in the two subject groups. The 131 SNPs distributed over 200,000 bp were represented by 41 variables, either SNP genotype or multilocus genotype for highly correlated SNPs; quantile of leucocyte telomere length (T/S ratio adjusted for age and sex) was used in model estimation.

Keywords: grade-of-membership analysis, coronary artery disease, TERC gene, telomere length, telomere set point

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 ,

A distinct gene-wide pattern in LRRK2 may identify a third of Parkinson's cases

Authors: Corder EH

Parkinson’s disease is becoming tractable. Risk is robustly associated with a short list of genes: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, SYT11/RAB24, and ITGA8 (Lill et al, 2012). Allelic frequencies for multiple SNPs located in these genes differ among PD cases as compared to control groups derived from the general population. However, association is a long way from an adequate description of risk and causation.

Keywords: grade-of-membership analysis, LRRK2, genetic epidemiology, Parkinson's disease

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

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: , , , ,

Optimized allotopic expression of mitochondrial genes: a strategy for treating mitochondrial DNA diseases

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

Mitochondrial diseases due to mutations in mitochondrial DNA can not be ignored anymore in most medical areas. With prevalence certainly higher than one in 6000, they probably represent the most common form of metabolic disorders. Despite progress made in identification of their molecular mechanisms, little has been done regarding therapy. We have recently optimized the allotopic expression for the mitochondrial genes ATP6, ND1 and ND4 and obtained a complete and long-lasting rescue of mitochondrial dysfunction in human fibroblasts in which these genes were mutated.

Keywords: Mitochondrial DNA, Allotopic expression, mRNA sorting to the mitochondrial surface, Optic neuropathies, Gene therapy

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 ,

Biomolecule PL1 immortalizes yeast in lethal stress conditions

Authors: H.R. Correia, S. Balseiro

It is generally assumed that all living beings die under specific and lethal stress conditions. However, here we show that a biomolecule called PL1, from one of the oldest known tree species, immortalizes yeast, the eukaryotic organism Saccharomyces cerevisiae, in fatal and combined oxidative and thermal stress conditions.

Keywords: Immortality, Yeast, Longevity, Lifespan, Lethal Stress

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

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 ,

Allotopic expression of Cytochrome B to rescue mitochondrial mutations

Authors: Crampton A, Irving J, Boominathan A, Vengalam J, Vanhoozer S, O'Connor M.

Cytochrome B (CyB) is an integral part of Complex III, and in its absence the entire Complex will fail to assemble resulting in a complete inhibition of oxidative phosphorylation.  Damage to the mtDNA is unavoidable as the mitochondria need this highly reactive environment to generate energy.  We are attempting to engineer methods to safely sequester these few genes in the nucleus and protect them from damage.  Our protein import approach utilizes built-in mechanisms that are designed to translocate and import nuclear encoded proteins to the mitochondria.

Keywords: allotopic expression, Cytochrome B, mitochondria

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

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 ,

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

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,

Selective Autophagy in the Fight Against Aging

Authors: Cuervo AM.

Accumulation of altered proteins and damaged organelles is a characteristic common to most types of cells and tissues in old organisms. Although often at a very slow peace, this progressive accumulation often compromises important cellular functions and eventually becomes detrimental and leads to cell death. Cells count on two surveillance systems to handle protein alterations: chaperones and proteolytic systems. Malfunctioning of these systems contribute in large extend to the abnormal accumulation of those altered proteins in cells and tissues in numerous diseases and in aging.

Keywords: Autophagy, Proteases, Lysosomes, Chaperones

Selective autophagy: fueling and cleaning the aging cells

Authors: A.M. Cuervo

Autophagy is the intracellular process that mediates the digestion of cellular components in lysosomes. The autophagic system fulfills two major functions in mammalian cells, serving both as an alternative source of energy, when nutrients are scarce, and as an efficient mechanism for the removal of any intracellular damage structure. Autophagic activity has been described to decline with age in almost all organisms and tissues, as wells as in several age-related disorders.

Keywords: autophagy, protein homeostasis, lysosomes, protein aggregation, lipid metabolism

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

Natural Cancer Resistance in Mice and in Humans: basis for a novel cancer therapy

Authors: Cui Z, Willingham MC, Keung Y, Pomper G, Stehle J, Blanks M, Kim-Shapiro L.

Why don't intentional exposures to known carcinogens, such as cigarette smoking, always cause lung cancer for most people? Living well into very old ages with heavy smoking but without getting lung cancer is not likely due to just being lucky. It is highly likely that most humans are protected intrinsically by an innate mechanism to confront cancer cells. If cancer is associated with a decline of such a protection mechanism, restoring this activity may offer a new avenue for cancer treatment.

Keywords: Cancer resistance, Granulocyte, Cancer therapy, Clinical trial, LIFT

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

The in vitro senescence phenotype of mesenchymal stromal cells and potential ramifications for innate immune function

Authors: Curran S, Campisi J.

Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that are found in specialized tissues, such as bone marrow, adipose tissue, and the umbilical cord; as well as systemically as pericytes or in the peripheral blood. MSCs are involved in multiple important processes, such as wound healing and tissue regeneration, but are of special interest for their capacity to suppress both the innate and acquired immune systems.

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

Healthy aging: how stay bonny & transcend inflammation?

Authors: d'Alessio P.

Introduction           People are driven by their obsession to stay young, and most importantly, in a visible way. Promising healthy aging, the market of dietary supplements is growing. Inflammation is a strategic key element in major degenerative diseases and has stimulated research on “inflammaging”. It is also recognized that inflammation contributes to depression. How can inflammation be managed without treating it with anti-inflammatory drugs?

Keywords: inflammation , supplementation with anti-inflammatory molecule, low grade inflammation in the elderly, ristomed EU study, anxiety and depression

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 ,

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: , , , ,

Intranasal delivery of cells to the brain

Authors: L. Danielyan, R. Schäfer, A. von Ameln-Mayerhofer, S. Verleysdonk, T. Klopfer, J. Geisler, M. Buadze, B. Proksch, G.H. Buniatian, C.H. Gleiter, W.H. Frey II

Organiser's Note: The presenter of this talk withheld their permission for video to be published.

Keywords: intranasal, non-invasive, delivery, stem cells, CNS

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 ,

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