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.
Association Of GSTM1 And GSTT1 Gene Deletions With Susceptibility To DNA Damage In The Pesticide Exposed Workers Of Punjab
The main aim of the present study was to evaluate genotoxic effects of pesticides in association with GST polymorphism. To achieve this aim DNA damage and genotypes of GSTM1 and GSTT1 genes were studied from blood lymphocytes of pesticide exposed and unexposed (control) agricultural workers of Punjab (north-west India). The blood samples were collected from 40 exposed and 27 unexposed subjects from Kakrala and Sanour villages of district Patiala. The DNA damage was evaluated by using alkaline comet assay.Keywords: Pesticide, Comet Assay, % DNA in tail, GSTT1 and GSTM1
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
Induction of Pluripotency (iP) has been shown to produce autologous stem cells that are viable for cell replacement therapy, with potential rejuvenative effect. Yet, the biological consequences of this process or iP-associated factors have scarcely been explored. Wound healing (WH) in adults, unlike early embryos, is usually a non-regenerative process in which the end-result is scar formation and a reduction in tissue function. iP and associated factors may have implications on the pathway of wound healing (e.g., scar-free or scar-formation).Keywords: wound healing, fibroblasts, induction of pluripotency
A novel Autologous Stem Cell Procedure for the Treatment of Aplastic Anaemia using Reprogrammed Mature Adult Cells: a Pilot Clinical Study.
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
Retrodifferentiation and Aging: Harnessing Youth through Induction of Pluripotency in mature adult cells via Cell Surface Receptor Contact
Organiser's Note: The presenter of this talk withheld their permission for video to be published.Keywords: Retrodifferentiation, Dedifferentiation, aging, Pluripotent Stem Cells, Regenerative Medicine
Recent findings suggest a strong correlation between Type 2 diabetes (T2D) and Alzheimer’s disease (AD). It is well known that an impairment of insulin signaling pathway can lead to insulin resistance and T2D, raising blood glucose levels. However, insulin and insulin growth factor-1 (IGF-1) contribute to neuronal survival, cognitive function and learning and memory processes as well. Indeed, many studies demonstrate that hyperinsulinemia, a pre-insulin resistance condition, is linked to higher risk of AD.Keywords: Alzheimer's disease, Type 2 Diabetes, Ageing, Insulin pathway, SHIP2
Polymorphisms of SHIP2, a phosphatase involved in the modulation of downstream signals in insulin pathway, in ageing and age-related diseases
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
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
Mitochondrial formation of superoxide has been recognized for a long time: it is believed to be equal to about 3% of total electron flux, although this amount has never been experimentally proven. It is also frequently accepted that ubiquinone is a source of superoxide production in mitochondria. However, comparison of the one-electron reduction potentials of ubiquinones and dioxygen and a great excess of ubiquinone relatively to the other mitochondrial electron carriers suggest that the equilibrium of reaction between ubiquinone and dioxygen must be shifted to the left, i.e.Keywords: superoxide, mitochondria, aging
Free radical theory of aging pointed out at major rogues responsible for human aging - reactive oxygen and nitrogen species. This conclusion was supported by many studies, but one of the most important question is still remaining unanswered: How aging processes start in healthy humans who do not suffer from any pathological disorders and all the stimuli of pathological disorders are excluded? Of course it is a purely hypothetical question, but if we can select "the physiological component" of aging initiation, it could be of importance for the understanding of a mechanism of aging.Keywords: Aging, Free Radicals, Physiological State
Early impairment of long-term depression in the perirhinal cortex of a mouse model of Alzheimer's disease
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
Differences in gene expression in the hippocampus of aged rats associated with better performance in inhibitory avoidance memory formation
Alterations of long-term declarative memory formation occur to different degrees among individuals during normal aging, but the genetic basis for such differences are not yet fully understood. Aim of the present study was the identification of genes differently expressed in the hippocampus of aged (26-27 month old) rats showing diverse cognitive performance in a single trial inhibitory avoidance (IA) task. IA is a hippocampal-dependent aversive learning, based on contextual fear conditioning.Keywords: inhibitory avoidance, memory formation, microarray, aging, hippocampus
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
Considerable muscle fiber loss occurs in quadriceps muscles of mammals with age. Our studies indicate that the molecular basis of this fiber loss is the accumulation of mtDNA deletion mutations within a muscle fiber to levels that result in mitochondrial electron transport system (ETS) abnormalities, intra-fiber atrophy, fiber breakage and fiber loss. If mtDNA deletion mutations play a role in muscle fiber loss with age, a number of testable hypotheses would have to be valid.Keywords: mtDNA, sarcopenia, muscle, calorie restriction, ETS abnormalities
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.
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
Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Illness and a Novel Phospholipid Fraction for Clinical Use for Reversing RTF Shift
A large body of evidence links the species of life span and oxidative stress. Not unexpectedly, mitochondria have drawn much attention as the site of that oxidative stress in the aging process. To cite a specific example, extension of murine life span with overexpression of catalase targeted to mitochondria has been shown.
Why is senescence not inherited? We propose that ageing arises from redox chemistry in mitochondria in somatic cells and male gametes, while passive, "template" mitochondria are sequestered in female germ-lines, allowing an indefinite number of accurate mitochondrial replications without damage to the mitochondria, their genomes, or to the cells that carry them .Keywords: aging, mitochondrion, oxidative-phosphoryation, sex, cloning
A known function of macrophages is to remove dead cells. In the adrenal cortex (AC), macrophages are mainly observed in the zona reticularis (ZR), situated deep in the gland. This finding is in agreement with the theory that AC parenchyma cells originate in the outer layers and migrate to the ZR where they die and are eliminated.Keywords: adrenal, macrophage, ageing, dexamethasone
Marrow stromal cells (MSC) have several unique properties, which make them well suited both for regenerative medicine and gene delivery. These include the ease of isolation and the ability to be considerably expanded in culture without losing engraftment capacity. Furthermore, MSC have been reported to reduce local inflammation, blunt immune response, and counteract the chemotactic signals released to recruit immune cells to the site of injury/inflammation.
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
Mitochondria decay with age due to oxidation of RNA/DNA, proteins, and lipids. Oxidative mitochondrial decay is a major contributor to aging. We are making progress in reversing some of this decay in old rats by feeding them normal mitochondrial metabolites (acetyl carnitine and lipoic acid) at high levels (1-3). The principle behind this effect appears to be that with age increased oxidative damage to protein causes a deformation of structure of key enzymes, with a consequent lessening of affinity (Km) for the enzyme substrate.
Mitochondrial decay, (a decrease in membrane potential, respiratory control ratio, cardiolipin, and cellular oxygen consumption, and an increase in oxidant by-products) appears to be a major contributor to aging and associated degenerative diseases. Oxidative damage to DNA, RNA, proteins, and lipids in mitochondrial membranes is a major consequence of this decay, resulting in functional decline of mitochondria, cells, and organs. Feeding the mitochondrial metabolites acetyl carnitine and lipoic acid to old rats rejuvenates the mitochondria and improves brain and other function.Keywords: Degenerative diseases, Brain, Micronutrients, Cancer, Adaptive immunity
Caloric restriction (CR) without malnutrition delays aging and extends lifespan in diverse species; however, mechanisms have remained elusive. Furthermore, the translatability of CR to primate species, and thus the applicability of insights from CR to human health, remains an open question. Here I will discuss the longitudinal adult-onset CR study in rhesus monkeys initiated at UW Madison in the late 1980s. In this population of rhesus macaques moderate CR lowered the incidence of aging-related deaths. In addition, CR delayed the onset of age-associated pathologies.Keywords: aging, caloric restriction, rhesus monkeys, metabolism
Caloric restriction without malnutrition extends lifespan and delays the onset of age-associated disorders in diverse species, from unicellular organisms to laboratory mice and rats. Until recently, evidence of the translatability of CR’s effects to human health has been a critical gap in CR research. In the late 1980s two parallel rhesus monkey caloric restriction (CR) studies were initiated to determine the effect of CR on resistance to illness and mortality in nonhuman primates.Keywords: calorie restriction, primate, survival, study design, genetic
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
Two fundamental questions confront biogerontologists working with caloric or dietary restriction: (1) How does food intake influence the rate of aging? (2) Should people practice caloric restriction while awaiting the answer to question #1? (In other words: does it work in humans, and if so, is it safe and practical?) This presentation will review the evidence from several laboratories that absolute caloric intake does not matter in terms of aging rate and will discuss ways in which this evidence suggests approaches to finding the answers to these questions.Keywords: lifespan , calories, restriction , aging , longevity
Clearing damaged biomolecules is important, however our bodies do it normally. Even amyloid proteins are degraded by native cells. Previous study showed some extension of mouse life span by mitochondrial catalase. According to the result, however, there still is a significant damage in mtDNA. This might be because mtDNA is attached to matrix side of the inner membrane, thus decreasing the effectiveness of the catalase.Keywords: membrane, oxidative, mtDNA, mitosens, mitochondria
For the last six years I have been implementing a program I initiated: The Intergenerational Program: Preserving Heritage in a Technological Environment. In this program young students, grades 5-11, tutor senior citizens at computer and Internet skills and learn from their older students, a chapter in the latter's personal history. Together they write a digital version of the story, scan pictures, albums, and documents, and search for information on the Net as well as in other sources.
The Geroscience Interest Group (GSIG): tracing pathological consequences of fundamental aging processes
This presentation will focus on the emerging field of geroscience, an interdisciplinary field that aims to understand the relationship between the basic biology of aging and age-related diseases. Geroscience is “coming of age.” Originally coined by Gordon Lithgow, “geroscience” was just entered into Wikipedia in June of 2013. A central concept of geroscience is that multiple human diseases arise from a common cause, aging itself.Keywords: geroscience, GSIG, NIH, healthspan
Possible Novel RNA-Mediated Transcriptional Activation Mechanism, called "RNA memory" Involved in Cell Identity
Position-effect variegation (PEV) was discovered in Drosophila melanogaster in 1930 in a study of X-ray-induced chromosomal rearrangements. If a rearrangement places euchromatic genes adjacent to a region of centromeric heterochromatin, it gives a variegated phenotype that results from the random inactivation of genes by heterochromatin spreading from the breakpoint. After the establishment, the inactivation is henceforth clonally inherited.Keywords: PEV, RNA, Transinduction, Cell Identity, Transdifferentiation
Messenger RNA (mRNA) translation efficiency is regulated by microRNAs. Each microRNA is able to regulate the translation of multiple mRNAs and each mRNA is regulated by multiple microRNAs. Thus, cellular mRNAs pool competes for microRNAs pool and viceversa. The regulatory network between mRNAs and microRNAs can be studied in the perspective of Competing Endogenous RNAs, or ceRNAs.
Here it is presented a bioinformatic study on ceRNAs for human telomerase (hTERT). Several genes potentially involved in the regulatory network of hTERT have been harvested by this study.Keywords: hTERT, telomerase, PTEN, dynein, CeRNA
A Bioinformatics Analysis of Lamin A Regulatory Network: a Perspective on Epigenetic Involvement in Hutchinson-Gilford Progeria Syndrome
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
Degenerative metabolic markers such as lipofuscin or atheroma may be considered as classes of 'dead-end' substrates within the limited mammalian metabolism. However, some microbial enzyme pathways are very much more diverse and in some cases may be able to convert such substrates into metabolically useful products. Recent genomic studies and cell assays indicate that mycolic acid bacteria from the genus Rhodococcus can metabolise such compounds.Keywords: lipofuscin , atherosclerosis , Rhodococcus , catabolism
Alpha lipoic acid increases sodium potassium ATPase and reduces lipofuscin accumulation in discrete brain regions of aged rats
A convincing link between oxidative stress and neurodegenerative condtions has been made with the knowledge that oxidative changes may actually trigger deterioration in cellular functions. We analysed the effect of DL-alpha-lipoic acid on the level of lipofuscin and the activity of sodium pottasium ATPase in discrete brain regions of young and aged rats. In aged rats, the level of lipofuscin was high, while the activity of sodium potassium ATPase was low.Keywords: alpha lipoic acid, ageing, lipofuscin
The purpose of the present investigation was to measure the activity of acetylcholiesterase in discrete regions of young and aged rat brain before and after DL-a-lipoic acid supplementation. Two groups of male albino rats were used in this study (4 and 24 months of age). DL-a-lipoic acid was administered intraperitoneally with a regimen of 100 mg/kg body weight/day using alkaline saline as a vehicle for 7 and 14 days.Keywords: lipoic acid, ageing, brain and acetylcholinesterase
Appreciating the Designs of the Blind Watchmaker: How characterization and creation are creating a new biological engineering science.
There is a philosophical danger in using the language of engineering to describe the patterns and operations of the evident products of natural selection. Invoking principles of design runs the risk of invoking a designer. But as we analyze the increasing amount of data on the genome and its organization across a wide array of organisms we are discovering there are patterns and dynamics reminiscent of designs that we, as imperfect human designers, recognize as serving an engineering purpose including the purpose to be designable, or rather, evolvable.
The genetic analysis of aging has dramatically improved our understanding of the aging process by highlighting the role of longevity determinant mechanisms (e.g., the insulin-like signaling pathway). But there are important remaining difficulties. We need to explain how the aging process can utilize highly conserved common mechanisms, yet still be expressed as a highly individual process. We need to better understand how these mechanisms interact with the environment and the individual life history. We need to develop an alternative to the use of time as a measure of aging.Keywords: gene networks, senescence, health span, oxidative stress networks
100 Plus: How the Coming Age of Longevity Will Change Everything, From Careers and Relationships to Family and FaithVideo: (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
One of the leading causes for low back pain is the age-related degeneration of the intervertebral disc (IVD). Mesenchymal Stem Cells (MSCs) are excellent candidates for skeletal tissue engineering, and therefore we aimed to investigate stem cell-based platforms towards the treatment of IVD disorders. We have engineered MSCs to express the osteogenic gene, rhBMP-6, using a novel electroporation-based system, and injected them into the lumbar region of mice. The cells were able to fuse 2-3 vertebrae within 5 weeks, as indicated by quantitative, in vivo, micro CT analysis.Keywords: Mesenchymal Stem Cells, Skeletal Tissue Engineering, Gene Therapy, Disc Degeneration
Infection by a virus of an individual (aged 20-30) will cause a response from the T (thymus derived) lymphocytes of which there are approximately 3 x 1011. If the individual has not met the virus before, the response will come from the naïve T cell subset (50±10% of the total T cell pool at this age) containing recent thymic emigrants produced from the thymus at approximately 108 per day. Their antigen specific receptor has a defined specificity governed by the conformation of its 2 chains (?
Selective cell growth and novel biomaterials have led to the engineering of tissues and organs that may be used to restore and maintain normal function. Cells for tissue reconstitution can be derived from the native organ to be replaced, thus avoiding rejection. In situations where normal native tissues are not available, different stem cell sources may be explored. In addition, recent advances in the field of cloning have made it possible to retrieve cells using nuclear transfer techniques.
The Preamble to the Constitution of the World Health Organization states that "the enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being?." From that perspective, one might expect exceptional public enthusiasm and support for research into medically-induced longer, healthier human life. However, such enthusiasm and support has been marginal, especially compared to the much greater support and enthusiasm for medical research campaigns against specific late-life diseases such as cancer and diabetes.
Currently Available Therapies with Autologous Stem Cells - From Basic Principles to Clinical Application
Organiser's Note: The presenter of this talk withheld their permission for video to be published.Keywords: Regenerative Medicine, Bioreactors, Liver, Biological Implants, Tissue Engineering
Regenerative medicine can be defined as efforts to change the default mechanism of mammalian wound healing from one of inflammation and scarring to regeneration of injured or missing tissues. Such a therapeutic approach represents a dramatic paradigm shift in the practice of medicine. What factors facilitate the development of effective regenerative medicine strategies?
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
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
By imposing a limit on the proliferative lifespan of some human cell types, telomere loss and the subsequent onset of replicative senescence has been proposed to contribute to age related disease. Whilst there is a large of body of in vitro data to reveal the mechanisms by which telomere erosion triggers senescence, technical limitations have hampered our ability to understand the full extent of telomere erosion in vivo.Keywords: telomere, telomerase, ageing
Hemoglobin levels influence exercise tolerance but not the benefits of exercise training in chronic heart failure patients
We regret that the details of this abstract are currently unavailable.
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