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.

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Conference: SENS5

A novel Autologous Stem Cell Procedure for the Treatment of Aplastic Anaemia using Reprogrammed Mature Adult Cells: a Pilot Clinical Study.

Authors: I.S. Abuljadayel, D. Mohantyb, R.K. Suric

Background and objectives: The disease, aplastic anaemia is a life threatening rare bone marrow failure. In this condition the underlying haematopoietic cellular deficit, lead to hemorrhage, infection and severe anaemia. The treatment of choice for this haematological condition is allogeneic bone marrow transplantation from fully matched HLA sibling. Though this procedure is curative in the majority of young patients with aplastic anaemia; extending this benefit to older patients or those lacking a family donor remains a major challenge.

Keywords: Retrodifferentiation, Aplastic Anaemia, Autologous Stem Cells, Reprogrammed Mature Adult Cells, Leukocytes

Polymorphisms of SHIP2, a phosphatase involved in the modulation of downstream signals in insulin pathway, in ageing and age-related diseases

Authors: G. Accardi, C. Caruso, G. Colonna Romano, R. Monastero, G. Candore

Phosphoinositides are components of the cell membrane and act as fundamental signaling molecules for regulation of cell proliferation and survival, cytoskeletal reorganization, and vesicular trafficking by recruiting effector proteins to cellular membranes. To regulate the cellular levels of lipid secondary messengers such as PtdIns(3,4,5)P3, cells use two major types of phosphoinositide phosphatases: the inositol polyphosphate 3-phosphatase PTEN and SH2 domain-containing inositol 5-phosphatases 1 and 2 (SHIP1 and SHIP2).

Keywords: SHIP2, SNP, ageing, age-ralated disease,

Early impairment of long-term depression in the perirhinal cortex of a mouse model of Alzheimer's disease

Authors: F. Tamagnini, C. Burattini, T. Casoli, M. Balietti, P. Fattoretti, G. Aicardi

Tg2576 is one of the most widely used mouse transgenic line in Alzheimer’s disease (AD) research. It carries a double missense mutation on the amyloid precursor protein gene (APP), resulting in marked increases in β-amyloid (Aβ) 1–40 and Aβ1–42 in the plasma and brain by 3–5 months of age, decrease in spine density in the outer molecular layer of the dentate gyrus at 4 months, decline in long-term potentiation of synaptic transmission in the dentate gyrus associated with impairment in contextual fear conditioning by 5 months, and plaque deposition in brain starting at 8 months.

Keywords: Alzheimer’s disease, Tg2576 mice, perirhinal cortex, long-term depression, visual recognition memory

Impairments in synaptic plasticity in aged animals and in animal models of Alzheimer's disease

Authors: M. Balietti, F. Tamagnini, P. Fattoretti, C. Burattini, T. Casoli, D. Platano, F. Lattanzio, G. Aicardi

Aging is associated with a gradual decline in cognitive function, and more dramatic cognitive impairments occur in patients affected by Alzheimer’s disease (AD). Studies performed in the last two decades in aged animals and in animal models of AD have revealed that deterioration of cognitive performances is associated with significant changes in synaptic plasticity.

Keywords: synaptic plasticity , aging, Alzheimer’s disease, declarative memory, nutrition

LysoSENS: a synthetic biology approach to treat age-related macular degeneration

Authors: L. Albanello
Video: (Video)

A2E is a toxic compound that is formed in the lysosomes of retinal pigment epithelial (RPE) cells, as a normal by-product of the vitamin A metabolism that is essential for photoreceptor activity. It is a major component of RPE lipofuscin, which is thought to mediate light-induced oxidative damage associated with aging due to its photosensitive nature; its presence leads to the formation of epoxides that are even more toxic to the host cell. I'm studying the potential of enzyme replacement strategies to help the RPE get rid of A2E, breaking it down into less toxic catabolic products.

Keywords: Macular degeneration, Lysosome, A2E, Gene assembly, LysoSENS

Small-molecule stimulators of telomerase

Authors: W.H. Andrews

Although our life expectancy has increased tremendously over the last century, there is still a 125-year theoretical limit on our lifespan, and no medical therapy available today has been able to break through this barrier. There is a clock that ticks inside every dividing cell of our bodies. This clock is found at the tips of our chromosomes, in a region of the chromosome called the telomere. When human cells divide, telomeres shorten, and the length of the telomeres correlates with the age of these cells.

Keywords: telomerase activation, telomeres, telomere shortening, ,

A Bioinformatics Analysis of Lamin A Regulatory Network: a Perspective on Epigenetic Involvement in Hutchinson-Gilford Progeria Syndrome

Authors: W. Arancio

Hutchinson-Gilford progeria syndrome (HGPS) is a rare human genetic disease that leads to premature ageing and ageing-associated phenotype. HGPS is caused by mutation in the lamin A (LMNA) gene that leads, in affected young individuals, to the generation of progerin, a splicing mutant of lamin A. A bioinformatics analysis of the LMNA gene network of interactions is presented. Lamin A seems to be involved in epigenetic regulation of transcription, chromatin remodelling, DNA repair, with key roles in stemness regulation, normal ageing and telomere functions.

Keywords: Hutchinson-Gilford progeria syndrome, Lamin A, HTATIP, Chromatin Remodellers, Epigenetic Modifiers

100 Plus: How the Coming Age of Longevity Will Change Everything, From Careers and Relationships to Family and Faith

Authors: S. Arrison
Video: (Video)

Humanity is on the cusp of an exciting longevity revolution. The first person to live to 150 years has probably already been born. What will your life look like when you live to be over 100? Will you be healthy? Will your marriage need a sunset clause? How long will you have to work? Will you finish one career at 65 only to go back to school to learn a new one? And then, will you be happily working for another sixty years? Maybe you'll be a parent to a newborn and a grandparent at the same time. Will the world become overpopulated?

Keywords: Social & Economic Implications of Longevity, Society and healthspan, , ,

Positive Lysosomal Modulation to Treat Age-Related Protein Accumulation Diseases

Authors: B.A. Bahr
Video: (Video)

Lysosomes are involved in degrading and recycling cellular ingredients, and their disruption with age may contribute to amyloidogenesis, paired helical filaments, and α-synuclein and mutant huntingtin aggregation. Lysosomal cathepsins are up-regulated by accumulating proteins and more so by Z-Phe-Ala-diazomethylketone (PADK). The latter positive modulator was evaluated in the well-characterized hippocampal slice model of lysosomal dysfunction that exhibits tau aggregation, tubulin breakdown, microtubule destabilization, transport failure, and synaptic decline.

Keywords: lysosome, lysosomal enhancement, Alzheimer's disease, synaptic pathology,

Development of non-peptidyl lysosomal modulators

Authors: M.L. Wisniewski, D.J. Hoover, Y. Sumskaya, J. Hwang, K. Viswanathan, D. Butler, A. Charalambides, D. Wright, B.A. Bahr

Lysosomes are the primary site for removal of old and misfolded proteins and to maintain cellular homeostasis, and positive lysosomal modulation has been shown to enhance protein clearance to protect against protein accumulation pathology. Small-molecule lysosomal modulators, for instance Z-Phe-Ala-diazomethylketone (PADK), at appropriate concentration elicit marked up-regulation of cathepsins and other lysosomal enzymes without any indications of synaptic compromise, behavioral abnormalities, or major organ malfunctions.

Keywords: lysosomal enhancement, protein accumulation diseases, positive lysosomal modulation, ,

Can the blood leukocyte telomere length predict sporadic thoracic aortic aneurysm?

Authors: C.R. Balistreri, C. Caruso, C. Pisano, G. Bianco, K. Fattouch, M. Caruso, E. Maresi, G. Ruvolo, G. Candore

The prevalence of cardiovascular diseases (CVD) rises with ageing and is one of the main causes of mortality in Western countries. In view of the progressive population ageing, there is an urge for a better understanding of age-associated diseases, such as sporadic thoracic aortic aneurysm (S-TAA), and their underlying molecular mechanisms. Several cardiovascular risk factors (i.e. hypertension, oxidative stress, smoking, etc.) seem to explain most of risk of S-TAA in general population. However, little is known about its precise cellular, molecular mechanisms and genetic determinants.

Keywords: S-TAA, biological ageing, mean blood leukocyte telomere length, ,

Mitochondrial gene transfer to transplantable tumours lacking a mitochondrial genome

Authors: M.V. Berridge, A.S. Tan

Mammalian cells contain multiple mitochondria with each mitochondrion containing several genomes. With few known exceptions, mitochondria are retained within their cell of origin. Nevertheless, intercellular mitochondrial transfer via membrane nanotubes has been demonstrated in cell culture systems in vitro and recent phylogenetic evidence has indicated that mitochondrial gene transfer from host to tumour cells occurs in a canine transmissible venereal tumour (Rebbeck et. al., Science 331: 303 2011). Intercellular mitochondrial gene transfer has not been demonstrated physiologically.

Keywords: mitochondrial genome, tumorigenesis , metastasis, cell metabolism, horizontal gene transfer

Vascular and Neuronal Damage in Cryonics Patients

Authors: B.P. Best

Cryonics patients can suffer varying degrees of ischemic damage, including both warm and cold ischemia. Although efforts to minimize warm ischemic damage for cryonics patients are often successful, most cryonics patients suffer lengthy cold ischemia during shipment in water ice to a cryonics facility for cryoprotectant perfusion. Vascular damage due to ischemia impedes perfusion with cryoprotectant solutions intended to eliminate ice formation.

Keywords: cryonics, ischemia, edema, vascular, damage

Damage Assays Rather than Biomarkers of Aging

Authors: B.P. Best

Damage Assays Rather than Biomarkers of Aging Aging is multiple forms of damage. Aging is primarily damage to macromolecules: proteins, lipids, carbohydrates, mitochondrial DNA and nuclear DNA (including telomeres). Aging damage is primarily due to ROS, RNS, sugars (glycation), radiation, pathogens, inflammatory cytokines, and accumulated toxins (metals, PCBs, dioxins, etc.). There is no singular aging process, but each species can be characterized by a maximum lifespan.

Keywords: aging, biomarkers, damage, assays, rejuventation

Kinetics of AGE-formation on BSA with various reducing sugars and dicarbonyl compounds in equimolar ratios

Authors: L. Luers, K. Rysiewski, C. Dumpitak, D. Willbold, E. Birkmann

Reducing sugars or reactive dicarbonyl compounds play a major role in glycation of proteins in vivo. Glycation of proteins is the first step in a non-enzymatic reaction resulting in advanced glycation endproducts (AGEs). AGEs can change the biological activities or even inactivate proteins [1; 2; 3]. AGEs formed by reducing sugars are also able to crosslink proteins leading to insoluble aggregates. Therefore it is important to understand the mechanism of AGE-formation.

Keywords: advanced glycation endproducts (AGEs), kinetics, reducing sugars, methylglyoxal, glyoxal

Combining data from evolutionarily distant species to predict long-lived mutants

Authors: B. Borgeson, C. St-Jean-Leblanc, E.M. Marcotte

Huge portions of the genomes of even the most well-studied organisms remain poorly understood. Accordingly, computational methods have attempted to predict functions and phenotypes associated with genes. Previously, our lab has constructed so-called functional networks--networks designed to predict the function of genes based on their similarity to other genes on a number of biological measures--and used these networks to show that even complex phenotypes such as longevity are relatively predictable.

Keywords: bioinformatics, networks, lifespan, ,

Aging brain mitochondrial dysfunction: metabolic rejuvenation

Authors: G.J. Brewer

Numerous reports document the decline in various aspects of mitochondrial function with physiological aging as well as the pathologic aging seen in Alzheimer’s disease, but remains unclear whether these deficits are the immediate response to an aging environment and the degree of their reversibility. By isolating neurons from the brains of rats and mice across the age-span and culturing them in a uniform environment, we eliminate the confounds of aging hormonal, vascular and immune systems.

Keywords: brain, mitochondria, ROS, estrogen, epigenetics

International Scientific Center for Research of the Future (Protection of Life)

Authors: V.V. Burdyuzha

Scientists worry state of our planet or more exactly they worry threats of life on the Earth. Global cataclysms took place in the past but then technological development did not allow to prevent these catastrophes. Other situation on our planet occurs now. Probably we can prevent local threats but we depend on the Sun in forward alternatively. Local threats are ecological, climatic, geodesic ones. The first and main threat is global warming in the result that greenhouse effect may develop.

Keywords: , , , ,

Mediterranean diet and longevity in Sicily: a survey in Sicani mountain population

Authors: C. Caruso, A. Marchese, C. Rizzo, S. Vasto

Since several years, increasing evidence suggests that the Mediterranean diet has a beneficial influences on several age-related diseases as metabolic syndrome and cardiovascular disease, hence showing protective effect on health and longevity. The effect of Mediterranean diet on human health has been reported in many population based studies and randomized trials, providing evidence for the positive effect on longevity of a dietary pattern rich in some nutritional food group.

Keywords: Centenarian, Longevity, Mediterranean diet, Olive oil,

Protocol of screening of sub clinical atherosclerosis by radio frequency (RF) coupled with 2D echo.

Authors: X. Castellon, V. Bogdanova

The study was carried in Athis Mons France between 2008 and the early 2011 on a cohort of 350 patients with cardiovascular risk factors. Introduction: Atherosclerotic lesions increase with aging and the changes favored by risk factors (diabetes, obesity, hypertension, dyslipidemia, smoking) and hence the interest of making an early detection of sub clinical atherosclerosis. The study of intima media thickness and speed of the wave pulse based on age, can detect patients at risk with increased threshold values, which reflects early atherosclerotic impregnation of the arterial wall.

Keywords: Early detection, atherosclerosis, age, , QIMT

Rescuing Aged Mesenchymal Stem Cells by Exposure to a Young Extracellular Matrix

Authors: Y. Sun, W. Li, R. Chen, Z. Lu, J. Ling, Q. Ran, R.L. Jilka, X.-D. Chen

Previously, we reported that in both mouse and human models a native extracellular matrix (ECM) generated by bone marrow cells dramatically promoted mesenchymal stem cell (MSC) proliferation, preserved the stem cell properties, and enhanced their capacity for skeletogenesis (Chen et al, 2007, JBMR, 22:1943; Lai et al, 2010, Stem Cells Dev., 19:1095). This led us to investigate whether culturing aged MSCs on an ECM could improve their number and quality.

Keywords: Age , Mesenchymal Stem Cells, Extracellular Matrix, Reactive Oxygen Species,

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: , , , ,

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, , ,

... Elegant elegans, Black-Scholes, alchemists and flat earthers...! Biology, longevity risk and their economic effects...

Authors: J.G.A. Donohue

In recent years developmental advances in biology at the molecular level have given rise to improving mortality and increasing longevity in the human species. As a consequence there has been a significant and growing risk affecting a number of financial institutions who have traditionally insured human life or provided financial provision for retirement. These institutions can no longer warehouse this risk or successfully fund it. This has raised a serious economic spectre.

Keywords: insurance, longevity, risk, retirement,

Telomerase activity in mouse brain and increasing it by novel chemical compound protects the brain

Authors: E. Eitan, E. Tichon, A. Gazit, D. Gitler, S. Slavin, E. Priel

Telomerase is expressed in neonatal brains and also in distinct regions of adult brain. Telomerase was shown to protect developing neurons from apoptosis. Telomerase transgenic mice demonstrated significant resistance to ischemic brain injury and N-methyl-D-aspartic acid (NMDA) neurotoxicity. Hence, we and other hypothesized that increasing telomerase expression by pharmaceutical compounds may protect brain cells from death caused by damaging agents.

Keywords: telomerase, ALS, neurodegeneretive, Neuroprotector,

Camelid antibodies in medicine

Authors: G. El Khoury, C.R. Lowe

The camelids - camels, llamas and their relatives - are unique in producing antibodies that have no light chain. These single polypeptide chain antibodies bind to antigens as strongly as conventional, multi-chain antibodies, but have lower molecular weights, are easier to engineer and produce, and more stable. They are attracting a lot of interest as potential therapeutics and diagnostics.

Keywords: antibody, antibody engineering, camelid, ,

De-novo geroprotector design

Authors: P. Fedichev, A. Vinnik, A. Moskalev

Geroprotector is a therapetics aiming at root causes of age-related diseases and as such capable of extending the life span of model animals and ultimately humans. The causes of aging are very ancient and evolutionary conservative. This means that the targets for the small molecule intervention can be identified using bio-informatics tools as the most conservative proteins in the pathways containing the largest number of genes responsible for the life span control.

Keywords: , , , ,

Cellular “functional replacement” with a “cell-free strategy” in early Alzheimer's and Parkinson's diseases: evidences from related animal models

Authors: C.I. Fernández, L. Castillo, I. Horruitiner, A. Toledano, M.A. León Díaz del Guante, M.E. González, L. Hidalgo

Background. Current evidence suggests that bone marrow stem cells (BMSC) contribute to lesioned/degenerated brain tissue repair by both secretion of trophic paracrine factors and functional incorporation into affected regions. Hypothesis. In vitro generated conditioned medium from cultured BMSC (CM-BMSC) replaces the stem cell grafting benefits in early Alzheimer’s and Parkinson’s diseases models respectively. Methods. BMSC-derived conditioned medium (BMSC-CM) was obtained from culture expanded BMSC (10 passages).

Keywords: animal model, neurodegenerative disease, stem cells, mild cognitive impairment, preclinical parkinsonism

Neurogenesis as therapeutic target in early Alzheimer´s disease: evidences from an animal model

Authors: C.I. Fernández, A. Toledano, M.E. González, E. Alberti, L. Hidalgo, M.A. León Díaz del Guante

Background. Neurogenic events and associated behavioral improvements have been reported after housing under enrichment environment conditions (EE), demonstrating the presence of newborn cells from neurogenic niches. Previous studies have demonstrated the bone marrow stem cells (BMSC) possibilities as source of tissue in brain grafting studies. Objectives: To compare functional effects induced by EE (12 weeks, 6 hours/day) and/or hippocampal BMSC grafting (H-Graft) in an early Alzheimer´s disease rat model. Methods.

Keywords: animal model , early Alzheimer's disease, stem cell grafting, cognitive impairment, environment enrichment

The future of human lifespans, a demographic perspective

Authors: C.E. Finch
Video: (Video)

The future of human life spans, a demographic perspective Caleb E Finch,Andrus Gerontology Center, University of Southern California, Los Angeles CA 90089-0191 Since the 18th C, human life spans have increased globally from a life expectancy at birth (LE0) of 25-40y, to >80y in healthy countries; the LE70 has also more than doubled (1-3). In essence the J-shaped mortality curve has shifted to progressively lower levels with minor changes in the accelerating (Gompertz) phase of mortality during aging (1,3).

Keywords: inflammation, Gompertz slope, minimum mortality , ,

Allocating resources for rejuvenation therapies

Authors: B. Foddy
Video: (Video)

We currently give absolute priority to medical interventions that save the life of individuals who are on the verge of death. Nobody in the UK is ever refused life-saving treatment unless it is unproven or ‘futile’. We do not take into account how much voluntary risk a person has taken on, their ability to pay, or even (in most cases) how expensive the therapies will be. If some curative intervention can provide a number of healthy additional years of life to a particular individual, it is provided.

Keywords: Ethics, Resource Allocation, Clinical Policy, Justice,

Computationally mining genome-wide drug-response compendia to discover novel calorie restriction mimetics

Authors: K. Fortney, E. Morgen, I. Jurisica

Calorie restriction (CR) extends lifespan in mammals and can delay the onset of age-related diseases, including cancer and diabetes. Drugs that target the same genes and pathways as CR may have enormous therapeutic potential. Recently, genome-scale data on the responses of human cell lines to over 1000 drug treatments have become available. Here we integrate these data with gene expression signatures of CR, biological pathway information, and protein-protein and drug-target interaction networks to generate a prioritized list of candidate CR mimetics.

Keywords: Bioinformatics, Drugs, Calorie restriction, ,

An amyloid-β binding peptide modulates Aβ oligomerization and is a possible candidate for therapy of Alzheimer’s disease

Authors: S.A. Funke, H. Liu, T. Sehl, D. Bartnik, O. Brener, L. Nagel-Steger, D. Willbold

A key feature of Alzheimer's disease (AD) is the pathogenic self-association of the amyloid-β (Aβ) peptide, leading to the formation of diffusible Aβ oligomers and extracellular amyloid plaques. Today, more than Aβ fibrils, small soluble Aβ oligomers are suspected to be the major toxic species responsible for AD development and progression. Next to extracellular Aβ, intracellular Aβ might have important pathological functions in AD.

Keywords: Alzheimer's disease, amyloid-β, therapy, peptides,

A Guided Tour Down the Pathways of Aging

Authors: J.D. Furber

At first glance the wall chart, "Systems Biology of Human Aging Network", looks like a complicated web. However, as a conceptual summary, in one view, we can see how most biogerontological processes relate to each other. Importantly, examination of these relationships allows us to pick out reasonably plausible causal chains of events. Within these chains, we can see age-related changes (or accumulations) that appear to be promising targets for future therapy development.

Keywords: Network, Causes, Pathway, Lysosome, Lipofuscin

Systems Biology of Human Aging 2011 Network Model

Authors: J.D. Furber

This network diagram is presented to aid in conceptualizing the many processes of aging, and the interactions among them, including promising intervention points for therapy development. This diagram is maintained on the Web as a reference for researchers and students. Content is updated as new information comes to light.

Keywords: Network, physiology, causes, pathology, pathways

AI Against Aging: The present and future role of AI and AGI in longevity research

Authors: B. Goertzel

The volume and complexity of available biological data vastly exceeds the scope of any individual human brain, one consequence of which is the likelihood that the vast majority of interesting, relevant patterns in already-published data remain undiscovered.

Keywords: artificial intelligence, bioinformatics, AGI, drosophila,

The circadian clock conducts development in mammals: Can stopping it be a means of control over aging?

Authors: V. Golub, M. Golub

It is obvious enough that aging is a "product" of the individual development of an organism (even because development gives "material" for aging). Although there would be no aging without development, there seems to be an infinite dispute between those scientists who consider aging (or life expectancy) as a biological program and those who do not. According to our point of view, the aging of an organism begins only after its development is completed, and perhaps even later.

Keywords: neobiosis, SCN, circadian clock, superdiapause, control over aging

Gene therapy and nanotechnology as interventive strategies for the aging brain

Authors: R.G. Goya, J.I. Schwerdt, O. Mykhaylyk, M.B. Casalini, B. Poch, R.B. Correia

Insulin-like growth factor I (IGF-I) is a powerful neurotrophic molecule which appears to be part of the physiologic self-repair mechanisms of the adult brain. Using the aging female rat as a model of age-related dopaminergic (DA) neurodegeneration, we have implemented short-term restorative IGF-I gene therapy in the hypothalamus and cerebral ventricles.

Keywords: Brain aging, IGF-I, Gene therapy, Magnetic nanoparticles, Magnetofection

Cellular Therapy for Intestinal Regeneration

Authors: E. Colletti, J. Wood, D.A. Ingram, E.D. Zanjani, M. Yoder, C. Porada, G. Almeida-Porada

Abnormal or inadequate vasculogenesis, local inflammation, and severe epithelial damage are common features of both inflammatory bowel disease (IBD) and radiation-induced injury resulting from pelvic or abdominal cancer treatment. Several studies have shown that adult bone marrow-derived stem cells, such as mesenchymal stem cells (MSC), upon transplantation, home to the damaged digestive tissue and facilitate mucosal repair in both IBD and radiation injury.

Keywords: Endothelial Progenitor Cells, Mesenchymal Stem cells, EphB2, Intestine, Inflamatory Bowel Disease

Epigenetic Drift and Aging

Authors: S. Gravina
Video: (Video)

Recent data suggest that the epigenome is highly dynamic and serves as an interface between the environment and the inherited static genome. The large volume of epigenomic events and its continuous need of maintenance, i.e., after DNA repair or replication, suggests a high chance of errors. The question we wish to address is how unstable the epigenome really is. Do epimutations accumulate with age and do they occur in a random fashion, i.e., as ‘epigenomic drift’? Do they ever reach levels that are high enough to have functional consequences?

Keywords: Epigenetic instability , Aging , Brain , Single-cells,

Aging of Synaptic Circuits

Authors: C.A. Greer

Little is known about how normal aging affects the brain. Recent evidence suggests that neuronal loss is not ubiquitous in aging neocortex. Instead, subtle and still controversial, region- and layer-specific alterations of neuron morphology and/or synapses are reported during aging, leading to the notion that discrete changes in neural circuitry may underlie age-related cognitive deficits. Although deficits in sensory function suggest that primary sensory cortices are affected by aging, our understanding of the age-related cellular and molecular changes is sparse.

Keywords: Olfaction, Synapse, Mitral cells, Granule cells, Glomeruli

Aging of budding yeast

Authors: A. Hallén

In a surplus of nutrition baker´s yeast cells (Saccharomyces cerevisiae) propagate parthenogenetically by budding off daughter cells. Propagation of old mother cells leads to daughter lines with exaggerated signs of aging (Lansing effect). The age of the mother cell depends mainly on the number of cell divisions (maximum about 20 buds), but to a small degree also on the chronological age (metabolic time). It is proposed that the aging may be ascribed to an accumulation of insoluble cross-linked protein, formed as a side product of protein metabolism.

Keywords: Aging, Insoluble protein, Lansing effect, ,

Neuron replacement in the neocortex

Authors: N. McKeehan, F. Diaz, J.M. Hébert
Video: (Video)

The cerebrum, as the substrate for our consciousness, memories, personality, and self-identity, presents unique challenges for regenerative medicine. Regenerative approaches must not only maintain general cerebral function, but also preserve as much as possible the details of the wiring and firing parameters that define each individual. A combination of molecular repair and gradual cellular replacement appears most likely to succeed.

Keywords: neocortex, glutamatergic neurons, cell migration, cell dispersion, apoptosis

How Can CR Inform Therapeutic Strategies?

Authors: L. Trindade, J.G. Heddle

Why organisms age and the reasons for the differences in longevity between different species is a fundamental question in biology. Changes in aging rates can be induced, most notably by increasing or decreasing calorie intake: Organisms subjected to caloric restriction (CR) live longer compared to those fed ad libitum (AL). CR robustly affects the age-related changes of several pathways: gene expression, hormones, oxidative damage, immune system, etc. All these mechanisms have a remarkable effect on longevity.

Keywords: Calorie Restriction, Ad libitum, Anti-Aging, ,

Detection of Parkinson's Disease associated α-synuclein fibrils by fluorescence microscopy

Authors: S. Huebinger, O. Bannach, A. Funke, D. Willbold, E. Birkmann

Introduction: Parkinson's Disease (PD) is one of the most common neurodegenerative diseases in humans, and the most common one associated with motor deficiencies [1]. It mainly affects the elderly with a peak age of onset at around 60 years [2], although familiar forms are known that show an earlier onset of disease. The symptoms are caused by the degeneration of dopaminergic neurons in the brain, which are accompanied by the misfolding and aggregation of the protein α-synuclein.

Keywords: Parkinson, Synuclein, Detection, Fluorescence Microscopy, Diagnosis

Approach to Assessing the Walking Motion of Elderly Males Based on Kinetic Parameters of Young Males

Authors: F. Ito,T. Mori,K. Kikkawa, H. Okada

This study seeks to propose a method to assess the walking motion of elderly males using criterial kinetic parameters for young males during walking and to suggest how to maintain their walking capabilities at the same level as those of young males. For this purpose, we used the coefficient of variation (= SD / MEAN * 100, CV), z-score and weighted z-score (= z-score /CV) to clarify parameters that differentiate the walking of elderly males from that of young males. The subjects were 13 healthy young Japanese males and 104 healthy elderly Japanese males.

Keywords: motion analysis, gait, aging assessment, inverse dynamics,

Thymic Tissue Regeneration Using Natural Scaffolds

Authors: J.D. Jackson, B. Lee, S. Soker, A. de Grey, A. Atala, J.J. Yoo
Video: (Video)

Tissue engineering offers the potential for treatment of many age related diseases. Decreased immunity is a major problem in the elderly resulting in the increase of infection related problems along with a decreased effectiveness of vaccination. T cells develop and mature in the thymus. During aging, the thymus undergoes involution resulting in a decrease in T cell production. Methods to increase T cell output from the thymus have the potential to improve the immune function of older individuals.

Keywords: thymus, tissue engineering, T cell, scaffold, immunity

Biospray techniques for engineering organotypic tissues

Authors: S.N. Jayasinghe

There are several approaches for developing organotypic tissues. These range of the non-jetting to the jetting methodologies. The non-jetting approaches could simply be exemplified by the manual mixing of a matrix with a given composition of cells.

Keywords: Biosprays, Viability, Mouse models, Engineering fucntional synthetic tissues, Regenerative biology and medicine

Differentiation of iPS cells into NK cells to combat cancer and HIV

Authors: D. S. Kaufman

Rejuvenation of the immune system through induced pluripotent stem cell (iPSC) technology provides a fundamentally new approach to treat and cure malignancies and chronic viral infections. iPSCs have now been made by hundreds of labs using diverse starting cell populations and reprogramming methods. Our group has used both iPSCs and human embryonic stem cells (hESCs) as starting cell populations to produce natural killer (NK) cells, key components of the innate immune system.

Keywords: induced pluripotent stem cells, human embryonic stem cells, natural killer cells, immunotherapy,

Improved Sequencing as a SENS Accelerant

Authors: K. Kemmish, M. Hamalainen
Video: (Video)

We are improving DNA sequencing to achieve our goal of turning biology into an information science. Along the way, various SENS approaches will be accelerated by improved DNA sequencing, and we present here specific experimental paths for using the tool in service of SENS. As one example, sequencing offers extreme technical shortcuts in molecular directed evolution techniques, allowing larger populations to be interrogated with fewer rounds of evolution and increased stringency of selection.

Keywords: sequencing, tools, directed evolution, stem cells,