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.
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
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.
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
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
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
Ageing is increasingly considered as an independent factor for the development of cardiovascular diseases (CDs). During ageing, there are structural and functional changes in the vasculature, including dilated lumen, altered intimal-medial thickness, vascular stiffness, endothelial dysfunction, increased endothelial apoptosis, matrix metalloproteinase dysregulation, increased expression of inflammatory molecules, aggravated oxidative stress and shortened telomere length.Keywords: ageing, vascular ageing , cardiovascular diseases, new therapeutic strategies
The productivity of medical innovation has been in decline, and this threatens the commitment of both public and private funders. However, there are both disruptive technologies and disruptive ideas that promise a turnaround. CASMI (www.casmi.org.uk) is exploring both, and developing testable models for change - including new open innovation-based discovery models, adaptive licensing of medicines, the use of real world data in development, and the personalisation of therapy on both genomic and behavioural grounds.Keywords: CASMI, Adaptive licensing, Open innovation, Real world data, Cell therapy
Age Related Macular Degeneration (AMD) is the leading cause of visual loss among people 65 years and older. This disease manifests into two distinct forms, wet and dry. The pathogenesis for both forms is poorly understood and numerous hypothetical models have been studied to better understand their mechanism. The dry form of AMD involves atrophy of the retinal pigment epithelium (RPE) by the accumulation of bisretinoid lipofuscin within lysosomes as the cells phagocytose the outer membranes of the photoreceptors.Keywords: age-related macular degeneration, AMD, lipofusin, A2E, retinal pigmented epithelium
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation that is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. The chronic airflow limitation characteristic of COPD is caused by a mixture of small airways disease (obstructive bronchiolitis) and parenchymal destruction (emphysema). Besides cigarette smoke, aging is a major risk factor for COPD.Keywords: COPD, Senescence, p53, Lung, Mouse
Distinctive profile of pro-inflammatory receptors in naive and memory B cells of young, healthy elderly and Alzheimer Disease patients.
It has been extensively demonstrated the impairment of humoral immune response in elderly humans, indeed they are characterized by a reduced ability to respond against new antigens and vaccines, due to a decrease both in percentage and absolute number of total B lymphocytes and modifications in the naïve/memory B cell compartments. Moreover, it is also well known that elderly are characterized by an “inflamed” environment (inflamm-aging).Keywords: B lymphocytes, chemokine’s receptors, inflamm-ageing, Alzheimer Disease, inhibitory receptors
The hypothalamus is a converging point that integrates metabolic, neural, neuroendocrine, and neuroimmune signals to affect the whole body physiology. The long-standing research interest of my research is to investigate the role of neural dysregulations, in particular in terms of neural inflammation in the development of aging and aging-related diseases. Our recent observations demonstrated that the hypothalamus contains adult neural stem cells, and IKK/NF-kB activation affects the fate of these cells and cause disease consequences in relation with aging and metabolic syndrome.
The Human Memome Project: Text-data analytics to find socio-cultural predictors of longevity utilising the quantified self, crowd sourcing and citizen science communities
Socio-cultural markers such as attitudes, behaviours, ideas, aspirations and interests were collected and correlated to previously identified social, psychological and quantitative predictors of lifespan. Attitudes to whether a person wanted to live for as long as possible and if so in what condition were also surveyed.
Keywords: text, data science, markers, quantified self, citizen science
Identification of three particular morphological phenotypes in sporadic thoracic aortic aneurysm (S-TAA): phenotype III as S-TAA biomarker in aged individuals
Ageing has a striking impact on heart and vascular system, and particularly on the large elastic arteries, i.e. aorta, determining a multitude of changes at different structural and functional levels. As result, medial degeneration (MD) occurs, which can progress in aortic dissections and rupture. A characteristic example of MD is thoracic aortic aneurysm (TAA), potentially devastating and an important source of morbidity and mortality. It happens as an isolated manifestation or defined syndromes or familial forms.Keywords: medial degeneration, S-TAA, , histopathological and immunohistochemical analyses, phenotype III as biomarker of S-TAA in aged individuals
RNA interference is a fundamental gene regulatory mechanism that is mediated by the RNA-induced silencing complex (RISC). Here we report that an artificial nanoparticle complex can effectively mimic the function of the cellular RISC machinery for inducing target RNA cleavage. Our results show that a specifically designed nanozyme for the treatment of hepatitis C virus (HCV) can actively cleave HCV RNA in a sequence specific manner.Keywords: nanozyme, hepatitis C, RNA interference, antiviral, nanoparticle
Nowadays is clearly evident that genetic background constitutes integral part of successful ageing and longevity. Many studies on long lived people have been conducted emphasizing the role of certain genes in long life. Classic case-control studies, genome wide association studies and high throughput sequencing have permitted to identify a variety of genetic variants seemingly associated to longevity. Over the years, ageing research has focused on insulin/IGF-1 signaling pathway because of its evolutionary conserved correlation with life-span extension in model animals.Keywords: Klotho, Ageing, Systematic review, Longevity
Effect of cognitive training on the expression of brain-derived-neurotrophic-factor (BDNF) in lymphocytes of mild cognitive impairment (MCI) patients
Keywords: BDNF, MCI, cognitive training, qRT-PCR, lymphocyte
Longer telomeres in mitochondrial lineages doubly-selected for extreme longevity and late female reproduction
Successful reproduction late in life in women is associated with familial longevity. Therefore, some genetic factors may slow both overall aging and reproductive aging in females. Here we investigate mitochondrial genetic contributions to longevity in both sexes and late reproduction in women.Keywords: telomere, mtDNA, reproduction, aging, longevity
The metabolic network is coordinately regulated in response to nutritional status to maintain homeostasis. Perturbed metabolic homeostasis is integral to the aging process and underlies many aging-associated diseases. Recent studies strongly suggest that metabolic enzymes are concertedly regulated via acetylation to allow coordination of the directionality and the rate of the metabolic flux upon changes in nutritional status. This mode of metabolic regulation is conserved evolutionarily and is regulated by the sirtuin family of deacetylase.
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
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.
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
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
Collective consequences of a very long life. The right to life extension could / should be considered a human right.
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
Modulating Biological Events by Biophysics: An innovative Molecular Methodology using Ion Cyclotron Resonance.
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
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
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
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
The in vitro senescence phenotype of mesenchymal stromal cells and potential ramifications for innate immune function
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.
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
Cellular senescence irreversibly arrests proliferation in response to potentially oncogenic stress. Senescent cells also secrete inflammatory cytokines such as IL-6, which promote age-associated inflammation and pathology. HMGB1 (High Mobility Group Box 1) modulates gene expression in the nucleus, but certain immune cells secrete HMGB1 as an extracellular Alarmin to signal tissue damage. We show that nuclear HMGB1 relocalized to the extracellular milieu in senescent human and mouse cells in culture and in vivo.
Human ageing is characterised by multiple changes at different levels of biological organisation. It is still not clear which (if any) molecular, cellular or physiological changes are more important drivers of the process of ageing or how they influence each other. One difficulty in understanding how different processes at different scales relate to ageing as a whole is the lack of integrative, holistic views of ageing.
The bowhead whale (Balaena mysticetus) has not only been estimated to live over 200 years, making it the longest-lived mammal, but these animals remain disease-free until much more advanced ages than humans can. The mechanisms for the longevity and resistance to aging-related diseases of bowhead whales are unknown, but it is clear they must possess aging prevention mechanisms.
Managing the process and changes that occur with aging is a complex challenge that will require much more than cutting edge research in biomedical sciences. It is only with an approach that marries different fields of science with environment and nutrition, that we will truly be able to alleviate the effects of aging.
Calorie Restriction (CR) without malnutrition slows aging and increases lifespan in simple model organisms and rodents. In Rhesus monkeys long-term CR reduces the incidence of type 2 diabetes, cardiovascular disease and cancer, and protects against age-associated sarcopenia and neurodegeneration. However, only in the Wisconsin, but not in the NIA monkey study, CR significantly increased average lifespan so far.Keywords: calorie restriction, human, lifespan
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
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.
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.
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
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.
Lipofuscin accumulates within the lysosomes of many healthy human cell types as one ages.
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
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
Advanced Glycation Endproducts (AGEs) form cross-links between proteins in the extracellular matrix (ECM) which are a major cause of the degradation of ECM function. AGEs accumulate with age in long-lived proteins such as collagen and elastin, significantly reducing tissue function. Removal of AGE cross-links is a potential route to reversing the disabilities of old age. AGE cross-links are however not the only AGEs in tissues. Conventionally, other AGEs have been used as markers of tissue glycation, in particular carboxymethyl lysine (CML).Keywords: Advanced Glycation Endproducts , Cross-links, Extracellular matrix
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, suggest 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?
The neocortex is the seat of our highest cognitive functions. Neocortical projection neurons, the principle neurons of the neocortex, become dysfunctional with age and can be lost due to neurodegeneration or insults such as stroke or trauma. The highly plastic nature of neocortical neuronal networks suggests that they could in theory withstand a slow turnover of neurons over time without significantly compromising function or memory. Therefore cell replacement may be a viable approach to rejuvenating the neocortex.Keywords: neocortex, cell replacement, neurons
The essential role of telomerase in stem cell maintenance has long been recognized. Nevertheless, we still have little understanding of the molecular mechanisms by which human cells regulate telomerase activity to ensure tissue homeostasis and how its dysfunction can lead to aging and tumorigenesis. The natural regulation of telomerase activity in human tissue and the impact of telomere shortening on untransformed human cells can only be studied in a primary human stem cell system.Keywords: ZFN, TALEN, telomerase, stem cells, site-specific nuclease