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.
The metabolic syndrome: IL-10 polymorphisms influence on serological and haematological parameters in type 2 diabetes
Previous studies have demonstrated that genetic regulation of IL-10 production might be implied in determining the complex phenotypes of successful or unsuccessful ageing and longevity. Recently it has been reported that low IL-10 serum levels are associated to an increased susceptibility for metabolic syndrome and type 2 diabetes mellitus. As well known IL-10 secretion ability is tightly controlled at the transcription level and it seemed tempting to investigate if polymorphisms in the IL-10 gene promoter contribute to type 2 diabetes mellitus.Keywords: metabolic syndrome, laboratory parameters, IL10 polymorphisms, unsuccessful ageing,
Computationally mining genome-wide drug-response compendia to discover novel calorie restriction mimetics
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.
The Longevity Variant Database (LVDB; http://denigma.de/lifespan/variants/) is a collaborative effort to catalogue all genetic variants that have been studied for their relation to human longevity. We have systematically identified and curated all GWAS, candidate gene, and candidate region studies conducted on long-lived human populations from the scientific literature. We have included both those studies linking new variants to human longevity, as well as those refuting putative longevity variants identified in previous works.Keywords: Genetics, Longevity, Database, Bioinformatics
We constructed the Human Longevity Network (HLN) and the networks for the major age-related degenerative diseases (ARDs) including atherosclerosis, cancer, Altzheimer's disease, and diabetes type II, based on protein-protein interactions. There is a remarkable overlap between the HLN and the ARD networks, suggesting that common pathways stand behind both aging and age-related pathology. The common genes are highly evolutionary conserved and fall into three main categories: signal transduction, DNA maintenance and repair, and protein and energy metabolism.Keywords: aging, age-related diseases, common gene signature, longevity, protein-protein interaction networks
MicroRNA-regulated protein-protein interaction networks: how could they help in searching for pro-longevity targets?
In spite of enormous efforts and accumulated knowledge, our capabilities for tackling aging and age-related diseases (ARDs), and ultimately to promote longevity are still very modest. What is lacking -- essential data on key players, efficient analytic tools, or both? Here we discuss how the existing data may be integrated and analyzed in the context of miRNA-regulated protein-protein interaction networks.Keywords: longevity, aging, age-related diseases, networks, RNA interference
Remyelination, the process by which new myelin sheaths are restored to demyelinated axons, represents one of the most compelling examples of adult multipotent stem cells contributing to regeneration of the injured CNS. This process can occur with remarkable efficiency in multiple sclerosis (MS), and in experimental models, revealing an impressive ability of the adult CNS to repair itself. However, the inconsistency of remyelination in MS, and the loss of axonal integrity that results from its failure, makes enhancement of remyelination an important therapeutic objective.Keywords: myelin, demyelination, remyelination, stem cells, aging
Aging is characterized by the functional decline of cells and organs, which ultimately leads to systemic failure of homeostasis and increased mortality. A critical question for our understanding of the aging process in metazoans is whether age-related pathologies are due to the isolated decline of individual tissues, or whether endocrine mechanisms exist that coordinate the rate of aging across the organism.
Evidence and identification of preferential protein targets for age-related modifications in peripheral blood lymphocytesAudio: (Audio)
Oxidatively modified proteins have been analyzed in aging human peripheral blood lymphocytes since protein modification by oxidation and other related pathways are believed to contribute to the intracellular age-related accumulation of damaged proteins, a process that has been associated with the cellular functional deficits that occur with age.Keywords: protein modification, oxidation, lymphocytes, proteomics, mass spectrometry
The relationship between calorie restriction and the biological clock: lessons from long-lived transgenic mice
The master clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain regulates circadian rhythms in mammals. Similar circadian oscillators have been found in peripheral tissues, such as the liver, intestine, and retina. Life span has been previously linked independently to both circadian rhythms and caloric restriction (CR). The mechanisms by which CR attenuates ageing and extends life span are virtually unknown.Keywords: ageing, biological clock, food, caloric restriction ,
Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia, affecting more than 20 million people worldwide. Today, AD can be diagnosed with certainty only post mortem, detecting insoluble beta-amyloid peptide (Abeta) aggregates and neurofibrillary tangles in the patient's brain tissue.Keywords: Alzheimer's disease, amyloid-beta, aggregates, early diagnosis ,
Organiser's Note: The presenter of this talk withheld their permission for video to be published.Keywords: Alzheimer's disease, amyloid-beta, aggregate detection, early-diagnosis,
An amyloid-β binding peptide modulates Aβ oligomerization and is a possible candidate for therapy of Alzheimer’s disease
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,
The many observable signs of human senescence have been hypothesized by various researchers to result from several primary causes. Close inspection of the biochemical and physiological pathways associated with age-related changes and with the hypothesized causes reveals several parallel cascades of events that involve multiple interactions and feedback loops. We have constructed a network diagram to aid in visualizing the many processes and interactions among them, including promising intervention points for therapy development.Keywords: aging, network model, causes, ,
The many observable signs of human senescence have been hypothesized by various researchers to result from several primary causes. Close inspection of the biochemical and physiological pathways associated with age-related changes and with the hypothesized causes reveals several parallel cascades of events that involve multiple interactions and feedback loops. We present a network diagram to aid in conceptualizing the many processes and interactions among them, including promising intervention points for therapy development.Keywords: Pathways, Causes, Systems, Flowchart, Network
Extracellular aging -- accumulating molecular damage by glycation, oxidation, and crosslinking of long-lived extracellular proteins, mainly collagen and elastin -- is a major cause of several important human aging pathologies. Crosslinking increases mechanical stiffness of blood vessels and urinary bladder. Crosslinking impairs functioning of kidney, heart, retina, and other tissues and organs. Glycation adducts trigger inflammatory signaling, provoking tissue damage and cancers. Crosslinking tightens up the extracellular matrix (ECM), hardening it against natural turnover processes.Keywords: crosslinks, extracellular, glucosepane, collagen, turnover
The many observable signs of human senescence have been hypothesized by various researchers to result from several primary causes. Close inspection of the biochemical and physiological pathways associated with age-related changes and with the hypothesized causes reveals several parallel cascades of events that involve multiple interactions and feedback loops. We present a network diagram to aid in conceptualizing the many processes and interactions among them, including promising intervention points for therapy development.Keywords: Systems Biology, Aging Network, Biochemistry, Physiology
Extracellular matrix (ECM) ages by several distinct mechanisms. This overview introduces the principal pathways and explores promising avenues for future therapy development. Pathways include: inflammatory glycoxidation and lipoxidation adducts: glycation crosslinks; amyloid deposits; protein residue isomerization, deamidation, and oxidation; fragmentation of collagen, elastin, laminin, and fibronectin; and loss of integrin binding sites. Promising future therapies could include drugs and enzymes that chemically repair the ECM, or cell therapies that biologically repair it.Keywords: Extracellular matrix, integrin, glycation, elastin, cell therapy
In old age, redox-toxic lipofuscin clogs lysosomes in critical non-dividing cells. This blocks autophagy and cell maintenance, impairs cell functions, and can kill essential cells. Inducing exocytosis of lysosomes could clear toxic lipofuscin out of the cell, allowing autophagy and cell repair to restore the cell to a more youthful, healthy state. Induction of lysosomal exocytosis has been demonstrated in human cells. The signaling pathways are being mapped. We are testing methods to safely induce exocytosis of lipofuscin-loaded lysosomes in old cells.Keywords: lipofuscin, lysosome, exocytosis, autophagy, rejuvenation
This network diagram is presented to aid in conceptualizing the many processes of aging, the causal chains of events, and the interactions among them. Contemplation of this network suggests 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.
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
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
The many observable signs and symptoms of human senescence have been hypothesized by various researchers to result from several primary causes. Close inspection of the biochemical and physiological pathways associated with each of the hypothesized causes reveals several parallel cascades of events with multiple interactions and feedback loops among them.
As an aid to keeping track of the many processes and interactions, a flow chart is presented. Promising intervention points for the development of new therapeutics are also highlighted on the flow chart.Keywords: aging, biochemistry, physiology, interactions, network
Acetyl-L-carnitine supplementation to old rats prevents the age-related soleus muscle mitochondrial decay by activating mitochondrial biogenesis
Decay of mitochondrial function is a major contributor to aging process, particularly for those post-mitotic tissues like skeletal muscle heavily dependent on oxidative metabolism (e.g. soleus). Aim of this study was to test if long-term ALCAR supplementation to aged rats was able to activate mitochondrial biogenesis in soleus muscle.Keywords: acetyl-l-carnitine, soleus muscle, mitochondrial biogenesis, aging,
Carnosine (b-alanyl-L-histidine) is known to be a natural neuropeptide with a variety of protecting properties preventing neuronal cell death under conditions of oxidative stress. Its antioxidant (Severin et al, 1984; Aruoma et al, 1989; Boldyrev et al, 1999), immunomodulating and wound healing (Nagai and Suda, 1989) as well as radioprotective and anti-ischemic (Boldyrev and Severin, 1990; Gallant et al, 2000; Stvolinsky et al, 2002) abilities could be useful tool to prevent accumulation of senescence features (Hipkiss, 1998).Keywords: carnosine, oxidative stress, life-span , ,
EXPANDING METCHNIKOFF POSTULATE: ORAL HEALTH IS CRUCIAL IN A GLOBAL SUCCESSFUL AGING MANAGEMENT STRATEGY
There is an aging of the mouth and face that goes along with the aging of the whole body and therefore to slow down aging itself we can’t do without considering an intervention on the oral health which is linked to systemic health and both depend on nutrition, epigenetic factors and microbiota interplay. The mouth is the mirror of the nutritional status and Dentist and Dental hygenist are often the first to notice nutritional problems, provide dietary advices and decide to refer the patient to a clinician.Keywords: oral microbiota, systemic pathologies, aging
Oxidative stress and TGF-beta1: triggers of premature senescence in adult human prostate fibroblasts?
Previous reports emphasize that oxidative stress-induced premature senescence (SIPS) of human diploid fibroblasts (HDFs) is mainly triggered by transforming growth factor beta 1 (TGF-b1). In the human prostate TGF-b1 mediates the differentiation of fibroblasts to myofibroblasts within a gradual process leading to a reactive stroma that favours epithelial cell tumorigenesis.Keywords: cellular senescence, oxidative stress, TGF-beta, prostate fibroblasts ,
Recent research has shown that humans have pathways to repair supposedly intractable molecular damage related to aging. Mitochondria DNA repair via homologous recombination, lysosome exocytosis and clearance of glycated proteins by L-carnosine are some of these pathways. Rather than technology, we propose that aging it is just a matter of resources, so that in order to rejuvenate our bodies we must acquire more resources than we lose. Candidate examples of positive resources are: food as similar as possible to breast milk, sunlight exposure to the whole body and ionized pure air.
Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues and organs perfectly. Given the conservation of genetic mechanisms among vertebrates, it is likely that the cellular and molecular processes that regulate urodele limb regeneration are shared among all vertebrates. It follows that since we all developed limbs as embryos, we possess the genetic program for re-making a limb (or any other organ) via these regenerative processes.Keywords: salamander, limb, regeneration, dedifferentiation, blastema
Lipofuscin accumulates within the lysosomes of many healthy human cell types as one ages.
Early-Life Programming of Aging and Longevity: The Idea of High Initial Damage Load (the HIDL Hypothesis)Audio: (Audio)
In 1991 we suggested a scientific idea that living organisms are developing with an exceptionally high load of initial damage, which is comparable with the amount of subsequent aging-related deterioration accumulating during the rest of entire adult life (Gavrilov and Gavrilova, 1991, "The Biology of Life Span"; http://www.longevity-science.org/index.html#Book).Keywords: Aging Theory, Early-Life Programming, Parental Age, Season of Birth, Lifespan Inheritance
25 years ago we first applied the reliability theory to explain aging of biological species (Gavrilov, 1978, PMID: 624242; Gavrilov et al., 1978, PMID: 716614). Since that time we continued the development of this theory (Gavrilov and Gavrilova, 2001, Journal of Theoretical Biology 213(4): 527-545, http://www.longevity-science.org/JTB-01.pdf) and came to the following conclusions:Keywords: Reliability Theory, Aging Theory, Redundancy, Compensation Law of Mortality, Mortality Deceleration
A common objection against starting a large-scale biomedical war on aging is the fear of catastrophic population consequences (overpopulation). This fear is only exacerbated by the fact that no detailed demographic projections for radical life extension scenario were conducted so far. What would happen with population numbers if aging-related deaths are significantly postponed or even eliminated? Is it possible to have a sustainable population dynamics in a future hypothetical non-aging society?Keywords: demographic projections, overpopulation, cohort-component method, war on aging, http://longevity-science.blogspot.com/
Does Exceptional Human Longevity Come With High Cost of Infertility? Testing the Evolutionary Theories of Aging
The purpose of this study is to test the prediction of evolutionary theory of aging that human longevity comes with the cost of impaired reproductive success (higher infertility rates, see Nature, 1998, 396: 743-746). Our validation study is based on the analysis of particularly reliable genealogical records for European aristocratic families. This dataset is appealing to use for two reasons: (1) it has high data accuracy and completeness; (2) confounding effects of socio-economic status are minimized in this socially elite group.Keywords: Longevity, Infertility, Reproductive Cost, Evolutionary Theories of Aging, Reproductive Success
Studies on exceptional human longevity may provide important clues on possible factors and mechanisms that delay human aging and promote healthy life span. This epidemiological approach to unraveling the mechanisms of human aging and longevity is applied in this study using two different datasets.Keywords: human longevity, maternal age, body build, farming background, fertility
Historical dynamics of natural death rate of the population and variations of atmospheric radiocarbon
The retrospective research of death rate of the population of some Western Europe countries -Norway, Denmark, Sweden, Germany - FRG, France, Switzerland, Great Britain, Belgium-, as well as of the USA and Australia, considering the periods of 19-th and 20-th centuries was carried out. The choice of the countries and historical depth of research of the population death rate were generally conditioned by the presence of national demographic statistical databases of necessary volume and quality.Keywords: the radioactive carbon, natural death rate, , ,
The fluctuations of natural death rate of the population corresponding with the variations of carbon - 14С concentration in the atmosphere were found out. Considering this point, and also taking into account the already known peculiarities of 14С radiating biological functioning, the hypothetical mechanism of radiocarbon influence on a person's ageing rate was offered.Keywords: the radioactive carbon, natural death rate, DNA, ,
In the work the tables describing death rate of the population of 48 European countries during the period between 1970 and 2000 years as well as the death rate statistics related to the population of 191 countries for 1999th, 2000th and 2001st years were used.Keywords: the radioactive carbon, natural death rate, ДНК , ,
An impaired zinc status associated with increased pro-inflammatory cytokine production are suggested as a risk factor for carotid stenosis (CS) development. Zinc protects from atherogenesis counterbalancing the oxidative stress and preserving the integrity of the endothelial cells during inflammation. In mammals, zinc uptake appears to be mediated by members of the Zrt/Irt-like protein (ZIP) superfamily of metal ion transporters.Keywords: Zip2, inflammation, carotid stenosis, elderly ,
Osteoporosis is a major cause of morbidity and mortality in older people. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue with a subsequent increase in bone fragility and susceptibility to fractures. There are a large number of risk factors for the development of senile osteoporosis. However, recent discoveries suggest that inflammageing, i.e.Keywords: Bone remodelling, Osteoporosis, Inflammageing, Immunosenescence, Ageing
On June 8th, 2003, the inaugural Methuselah Prize was awarded to Dr. Andrzej Bartke for the "Methuselah Mouse" that lived the equivalent of 180 human years. The Methuselah Foundation is offering prizes for specific achievements in the spirit of the Longitude Prize of 1714 for advancements in the healthy lifespan of both newborn and aged mice. The series of prizes will grow to include even more ambitious life extension competitions as progress is achieved.Keywords: life extension, prizes, mouse models , ,
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,
It is well known among researchers that the SIR genes are activated by the sensing of low NADH relative to NAD a measure of cellular redox state in animals from yeast to mammals. I have found that a mono-food high cyanogenic cassava root diet will produce low NADH levels as soon as all other nutrition clears the large intestine in 5-7 days. Other survival genes may also be activated when the large intestine becomes clear of bacteria, fat, iron and high protein as the large intestine is central to other longevity gene signaling involving nutrient sensing.Keywords: cassava, cyanogenic glucosides, NADH reduction, SIRT1-7 activation, iron chelation
Loss of muscle mass and function (sarcopenia) is one of the most marked problems associated with ageing as it has major health care as well as socioeconomic implications. The growth hormone/IGF I axis is regarded as an important regulator of muscle mass. However, it is now appreciated that other tissues in addition to the liver express IGF-I. Also there are local as well as systemic forms of IGF-I which have different functions. We cloned two different IGF-Is that are expressed by skeletal muscle and both are derived from the IGF-I gene by alternative splicing.Keywords: Sarcopenia, muscle mass, MGF, IGF-I, Exercise
Cardiovascular stressors induce lysosomal dysfunction, sirtuin-1 depletion and premature senescence of vascular endothelium
Chronic cardiovascular and kidney diseases are associated with premature vascular senescence, which contributes to vasculopathy and accelerated progression of original malady. At least three independent pathways participate in this predilection to premature vascular/endothelial senescence, as will be discussed in the presentation.Keywords: lysosomal membrane permeabilization, autophagy, metabolome, endothelial dysfunction, sirtuin-1than
The circadian clock conducts development in mammals: Can stopping it be a means of control over aging?
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
Endocrine system takes part in the organization of the processes and functions that are affected by aging in the first turn: complex forms of behavior, nonspecific adaptation to stress factors of environment, reproduction, homeostasis, immune states, higher nervous activity, etc. This is why it may be suggested that age endocrine disturbanses are important factors of the processes of physiological aging and age pathology.Keywords: Aging, adrenals, testes, pineal gland ,
We have developed conditionally immortalized cell lines and we have cloned several senescence associated genes. Analysis of the function of one of the isolated genes (ApoJ), suggests that it is a novel survival factor. ApoJ is found over-expressed in vitro under a variety of stress conditions and in vivo in patients suffering from various age-related diseases. Stable over-expression of ApoJ inhibits apoptosis and its inhibition by RNA interference sensitizes cells to cytotoxicity.Keywords: human, longevity, proteasome, senescence, survival
Telomere length changes are far more dynamic than previously thought. In addition to a gradual loss of ~100 base pairs per telomere in each cell division, large losses as well as gains may occur within a single cell cycle. How these processes, collectively referred to as telomere dynamics, influence cellular proliferation and the approach to senescence is poorly understood. We are investigating how telomere exchange, extension, and deletion affect the proliferative potential of telomerase-negative somatic cells.Keywords: telomere, senescence, ALT , ,
The aim of this study was to demonstrate the prospects of applications of the novel carbon-based pharmaceuticals, namely - enterosorbents and fullerenes in biomedical gerontology. We present the results of our own studies as well as the analytical review of the literature data that were available up to now. The dietary enterosorbent, SKN non-coated nitrogen-containing carbon, was found to increase the mean value of male Wistar rats' life-span by 43%, that is comparable with the life-span prolongation effects of the calorie-restricted diets (Frolkis et al., 1989).Keywords: aging, life-span prolongation, fullerenes, eneterosorbents ,
In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anti-cancer mechanism that limits cell proliferation.Keywords: Aging, cancer, telomerase, ,