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.
Modest progress has been made over the last two decades towards manipulating the mitochondrial genome and cures for mitochondrial DNA diseases are still elusive. Our laboratory is pursuing two different strategies to make altering the mitochondrial genome and subsequently mitochondrial gene therapy feasible. Our first approach is based on utilizing novel nano-technological tools , our second approach is based on the apparent natural capability of mammalian cells to internalize exogenous isolated mitochondria .Keywords: mitochondrial gene therapy, mitochondrial nanotechnology, , ,
Somatic cell nuclear transfer or fusion with embryonic stem (ES) cells can reprogram a somatic genome back into an embryonic epigenetic state. One potential application of reprogramming human somatic cells were the derivation of patient-specific stem cells for cell transplantation therapy. Potential therapeutic applications of these technologies are currently impeded by technical difficulties and ethical considerations.Keywords: stem cells, reprogramming, pluripotency , ,
Human Embyryonic Stem (ES) cells are unique in two important aspects. First, they are totipotent (capable of differentiating into any somatic cell type). Second, they are immortal germ-line cells and are, therefore, able to make young cells in vitro for therapy in age-related disease. An important problem to be resolved is how tolerance is to be achieved in transplants made from ES-derived cells.Keywords: , , , ,
An increasing number of the manifestations of aging are being attributed to telomere shortening and/or damage. Nuclear transfer offers the possibility of transiently reactivating telomerase activity, restoring germ-line telomere length, exchanging the somatic cell mitochondria with that of the oocyte, and reprogramming the chromatin of somatic cells to an embryonic pattern of gene expression.Keywords: Stem Cells, Telomeres, Telomerase, Nuclear Transfer, Mitochondria
Telomerase is of significant interest to many scientists for its ability to immortalize cells, usually expressed in most tumor cells and human embryonic stem cells, but it is silenced in normal differentiated cells. Cancer researchers are focused on the inhibition of telomerase activity in cancer cells for therapeutic purposes while anti-aging enthusiasts are interested in de-repressing telomerase expression. Induction of telomerase activity could contribute to maintaining telomere length and elongation of telomeres in normal somatic cells thus possibly extending replicative life span.
Age is by far the greatest risk factor for a number of common neurodegenerative diseases such as Parkinson disease (PD). Oxidative stress and mitochondrial dysfunction appear to be key features of PD pathogenesis, however, it is unclear whether or how these pathogenic mechanisms may be related to normal age-dependent changes. Profound insights into the possible pathogenic mechanisms have come from elucidating the function of genes linked to rare inherited forms of PD such as parkin, encoding an E3-ubiquitin ligase, and PINK1, which encodes a mitochondrial kinase.Keywords: , , , ,
Evaluation of the blood-brain barrier permeation characteristics of D-enatiomeric peptides that bind to amyloid peptide Aβ (1-42)
Previously, two D-enantiomeric amino acid peptides that specifically bind to amyloid peptide Aβ (1-42) were identified by using a mirror image phage display approach. One peptide, named 'D1', was found to bind to amyloid plaques with a binding constant in a submicromolar range. In vitro studies showed that it was a promising candidate for diagnosis of Alzheimer's disease (AD). The other peptide 'D3' exerted strong influence on Aβ aggregation and cytotoxicity in vitro. In vivo, it reduced amyloid plaque load and cerebral damage of transgenic mouse models of AD to an outstanding extent.Keywords: Alzheimer's disease, amyloid-beta, aggregation, peptides, blood brain barrier
Not only Aβ fibrils, but also small soluble Aβ oligomers in particular are suspected to be the major toxic species responsible for Alzheimer’s disease (AD) development and progression. The aim of the study was to identify peptides consisting of the D-enantiomeric amino acids (D-peptides) that bind highly specific to Aβ(1-42) oligomers. D-peptides are thought to be protease resistant and less immunogenic than the respective L-enantiomers and can easily be identified by mirror image phage display.Keywords: Alzheimer's disease, amyloid-β, therapy, peptides,
Oral treatment with an Aβ42 oligomer modulating D-amino acid peptide improves cognitive behavior of APP/ PS1 double transgenic mice
Organiser's Note: The presenter of this talk withheld their permission for video to be published.Keywords: Alzheimer's disease, amyloid-beta, aggregation, therapy, peptide drugs
It is widely recognised that the prevalence of cataracts rises considerably in older people. Our research in companion animals shows that the same is true in dogs, cats and horses. Cross-sectional studies in two thousand dogs and a similar number of cats has demonstrated a good correlation between the age at which lens opacities occur and the longevity of the dog or cat breed. But what it is in the lens of a Great Dane (with a relatively short lifespan) that causes cataract to develop earlier than in the lens of a minature poodle (with a long lifespan)?Keywords: cataract, lens, animal, anti-oxidant, ageing
Any major improvements to lifespan are likely to increase the prevalence of age related diseases such as Alzheimer's Disease (AD). AD is almost exclusively a disease in those aged 65 or older and the prevalence increases with age. It is predicted that even with today's ageing population the prevalence of AD will increase significantly. In AD the brain has a number of changes that can be linked to pathology including aggregates of tau and beta amyloid proteins.Keywords: Alzheimer's, aggregates , therapy , ligand ,
Therapeutic and preventative potential of Tau Aggregation Inhibitor therapy with rember for age-related cognitive neurodegenerative disorders
The quantity of aggregated Tau protein is correlated with clinical dementia in Alzheimer's disease (AD). The process of pathological Tau aggregation begins in mid-life and progresses exponentially with age. rember (active moiety methylthioninium, MT) inhibits Tau aggregation in vitro and reverses Tau pathology, cognitive and motor deficits in transgenic Tau mouse models. A Phase II trial of rember monotherapy conducted in 321 mild or moderate AD subjects suggested that Tau Aggregation Inhibitor (TAI) therapy may be useful for delaying or even arresting the progression of AD.Keywords: Alzheimer's, Tau, neurodegeneration, therapy, prevention
Successful delivery of macromolecular therapeutic agents across the blood brain barrier (BBB) to the central nervous system is a major challenge in the treatment of neurological diseases of aging. Recently, the exploitation of natural nanoparticles known as exosomes has been pioneered and demonstrates their potential as therapeutic delivery vehicles. The natural macromolecular delivery and targeting properties of exosomes are well exemplified with siRNA delivery systemically to brain to target genes implicated in Alzheimer’s disease.Keywords: exosomes, nanoparticles, blood-brain barrier, delivery mechanisms,
Dietary restriction (DR), limiting certain factors in diet, without causing malnutrition, is a non-genetic intervention that delays the ageing process and extends healthy lifespan in multiple organisms from yeast to rodents. To decipher the mechanisms of DR, we established a web-accessible database (GenDR) of DR-essential genes, which if genetically altered interfere with the effect of DR to extend the lifespan in model organisms (yeast, worm, fly and mice). DR-essential gene orthologs were identified and their molecular evolution investigated.Keywords: Dietary restriction, Molecular evolution, Network-approach, Guilt-by-association, Comparative interactomics
Aging is a complex phenomenon that requires an engineering approach in order to be solved. We initialized the construction of a digital decipher machine, Denigma [http://denigma.de], to reverse-engineer the aging process, make aging research more collaborative as well as efficient and facilitate the discovery of powerful therapeutics.Keywords: reverse-engeneering, information technology, machine-learning, crowdsourcing, web intelligence
The aging process remains an Enigma, though by combining the "power of the crowd", i.e. collective human intelligence, with increasing computational power of machine intelligence we can reverse-engineer the aging process. In order to decipher the aging process, the construction of a Digital Decipher Machine, Denigma [http://denigma.de], was initialized. Denigma is an open-source project that creates a web intelligence and promotes open distributed science for longevity research.Keywords: web, knowledge, reasoning, intelligence, anti-aging
Decline of the nuclear factor E2-related factor 2 (nrf2) and antistress gene response in ageing and strategies to prevent it for healthy ageing
Ageing is associated with accumulation of damaged proteins, decline in glucose tolerance, dyslipidaemia, oxidative stress, inflammatory disorders and increased cell senescence. The endogenous defence to protein damage, metabolic stress, inflammation and oxidative stress is coordinated by nuclear factor E2 related factor 2 (nrf2), kelch-related ECH protein-1 (keap1) and antioxidant response element (ARE) linked gene expression in the antistress gene response. The nrf2/keap1/ARE transcriptional system regulates the expression of a battery of protective genes.Keywords: nrf2, Antistress gene response, Oxidative stress, Dyslipidaemia, Dietary bioactives
Our research focuses on the regulation of myogenic stem cell function in adult life. Our long-term goal is to identify means to ameliorate age-related muscle deterioration (sarcopenia). Sarcopenia is characterized by a decline in mass, strength, and endurance of skeletal muscles, and by fat accumulation between and within myofibers. Subtle muscle injuries that occur during routine muscle activity raise a continuous demand for functional myofiber repair throughout life. However, myogenic stem cell performance declines in old age and this decline can be a contributory factor to sarcopenia.Keywords: Skeletal muscle, Stem cell renewal, Satellite cells, Microvasculature, Pericytes
It has been recognized that structural and functional defects of human mitochondrial NADH dehydrogenase (complex I) are involved in many diseases. Recently, sporadic Parkinson's disease and type 2 diabetes due to obesity are also considered to be related to complex I defects. Therefore, it seems important to develop therapies for complex I defects. Mitochondria of Saccharomyces cerevisiae lack complex I but instead have the rotenone-insensitive internal NADH dehydrogenase (Ndi1). The Ndi1 enzyme is composed of a single polypeptide and lacks proton pumping function.Keywords: NADH dehydrogenase, mitochondrial disease, therapy, complex I,
Nanog has been discovered that is essential for mouse and human embryonic stem cells (ESC) pluripotency and self-renewal. It also expressed in several adult murine tissues by using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. However, human Nanog transcripts have been isolated from adult bone morrow (EST, BF893620). Here, we study the Nanog gene expression profiling in the isolated mouse renal papillary cells that were confirmed by assessment of expression by Northern blots, RT-PCR.Keywords: Nanog gene, Senescence, kidney, ,
Wound healing (WH) is a fundamental biological process. Does the ability to heal faster have any impact on longevity? In an attempt to answer this question, we compared the established mouse models with genetically modified life span and also an altered rate of WH. Our analysis showed that the ability to preserve the rate of skin WH up to an old age, but not a high WH rate in the youngs, appears to be associated with a longevity phenotype.Keywords: Wound healing, Longevity, αMUPA mice, ,
Since Hayflick’s discovery of the phenomenon of cellular senescence (CS), the contribution or even relevance of this phenomenon to organismal aging has been a subject for continuous debates. Although the question still remains open, an increasing amount of evidence indicates that CS could have a role in aging and age-related diseases (ARDs), rather than being just a laboratory phenomenon. In fact, the current situation in the field could be defined as an attempt to understand to what extent and how is CS involved in aging and ARDs.Keywords: Cellular senescence, Cancer, Age-related diseases
Current research is focused on the development of the integrated biomarkers’ system and anti-aging regulatory programs. The main target systems are immune, neuroendocrine, hepatobiliary and gastrointestinal. The ultimate goal of this research is to improve these systems' conditions and functions. We have revealed the usefulness of the consortium of probiotics and prebiotics for gastrointestinal tract and hepatobiliary system. In regards to immune system, DNA-protecting effect of probiotics is being analyzed.Keywords: anti-aging, probiotics, , ,
Immunotherapy represents a promising strategy for the treatment of patients with cancer that is refractory to conventional therapy. One form of immunotherapy, adoptive T cell therapy, involves the ex vivo selection of antigen-specific T cells and their expansion to desired magnitude for achieving a targeted immune response. In contrast to vaccine strategies, adoptive cellular therapy is free of the in vivo constraints that limit the magnitude and phenotype of a desired response.Keywords: Immunotherapy, Melanoma, T Cell Therapy, Antigen,
A principle mechanism of biological aging has been understood due to accumulation of biological side-reactions such as oxidation and glycation stresses related with energy metabolism in the framework of metabonomics and systems biology. When over exercise, immune defects and inflammations are all found associated with aging-rate in human life, anti-stress or anti-subhealth is suggested, in this work, as a primary and effective anti-aging practice in pre-clinic endeavors.Keywords: Aging, Carbonyl stress, Glycation, Oxidation, Traditional Chinese medicine
Following enormous achievements of study of genomics and proteomics, a systems biology-directed metabonomics is emerging and directed a quick development of life sciences which calls for "emergent characters" to describe running life with some general indexes.
The human ovary is the female reproductive organ containing cells that secrete hormones (estrogen, progesterone), which maintain female sexual characteristics as well as egg (ovum) production. Loss of ovarian tissue function due to various endocrine and fertility disorders requires chronic estrogen (E) and progesterone (PG) administration. Conventional hormone replacement therapy is based on oral, injection and transdermal (skin patch) administration but these have several disadvantages, such as frequent administration, fluctuation in blood hormone levels and associated complications.Keywords: Ovary, Female hormones, Endocrine function, Follicles,
The products of two genes mutated in autosomal recessive forms of Parkinson’s disease, Pink1 and Parkin, have been identified in Drosophila to work in the same pathway to maintain healthy flight muscles and dopaminergic neurons. PINK1 is a kinase located on mitochondria whereas Parkin is an E3 ubiquitin ligase normally located in the cytosol. Upon mitochondrial damage Pink1 recruits cytosolic Parkin to mitochondria to mediate mitophagy revealing a cell biology pathway in mammalian cells where Pink1 works upstream of Parkin.
The Aspirin pro-drug aspirinamine penetrates skin, blood-brain, blood-milk, and other membrane barriers thousands of times faster than aspirin. Aspirinamine has shown a very strong anti-diabetic (both type I and type II) activity in NOD and STZ mouse models, and exerts neuroprotective effects after stroke.
It increased the maximal life span of C57BL/6 mice by 26% (at dose of 15mg/kg, equal to 10mg/kg of aspirin) and 27% (at dose of 45mg/kg, equal to 30mg/kg of aspirin).Keywords: Aspirin, pro-drug, longevity, anti-diabetes, anti-stroke
Sarcopenia consists in reduction of skeletal muscle mass, strength, and resistance, representing a major problem in gerontology and geriatric medicine because of the associated impairment of performance in older individuals. Physical exercise has been suggested to prevent/revert sarcopenia. In this investigation, we studied in senescent (> 20 months) mice the effect of chronic physical exercise on the T2 relaxation time (a key parameter in MR imaging) of skeletal muscle in vivo.Keywords: magnetic resonance, physical exercise, sarcopenia, muscle mass, morphometry
An estimated $10 billion is being spent annually on projects related to aging research by the government, corporate and non-profit organizations worldwide. Presently, no centralized system exists for tracking aging research projects across research areas internationally.Keywords: aging research funding decision making, , , ,
Aging research spans many areas of natural and social and behavioural sciences. Few data repositories aggregate data from the scientific literature, clinical trials databases, patents and grant application reports. To address this issue, we developed a flexible open-access knowledge management system for aging research the International Aging Research Portfolio (IARP) accessible via www.agingportfolio.org.Keywords: aging research, aging database, aging system, gerontology system, knowledge management
While the doubling of the life expectancies in the developed countries in the 20th century can be attributed mostly to decreases in child mortality, trillions of dollars spent on the biomedical research by the governments, foundations and corporations over the past sixty years are yielding longevity dividends in the older population. When increases in life span will occur after the retirement age and extend the "last mile", unless the retirement age is proactively adjusted, the net economic effect of these increases is negative.Keywords: aging economics, ageing economics, economics of longevity, life span economics
Caloric restriction (CR) is the only intervention shown to extend lifespan and retard age-related declines in function in mammals. Mutations that extend lifespan in C. elegans suggest that insulin/IGF-1 signaling (IS) pathway may play a key role in retarding aging and extending the lifespan by CR. To evaluate this hypothesis, we subjected male F-344 rats to 2 mo or 25 mo CR (starting at 28 days old, 40% of control level) and then assessed the effects of CR on early events in the IS pathway in liver and muscle.Keywords: Caloric Restriction, Insulin Receptor, Phosphorylation, PTP-1B, PPARs
In a world where more people grow older aging-related neurodegeneration like Alzheimer’s disease (AD) affects more and more people.Keywords: Alzheimer's disease, early diagnosis, amyloid β, aggregates, high resolution microscopy
Organiser's Note: The presenter of this talk withheld their permission for video to be published.
In this fast-paced presentation I will explore how to present the somewhat esoteric and potentially dangerous new science of Longevity in a positive light; thus preparing society for the radical transformation to much longer life, while creating a more fertile ground for political and financial support.Keywords: , , , ,
Nuclear insulin-like growth factor binding protein-3 induces apoptosis and is targeted to ubiquitin/proteasome-dependent proteolysisAudio: (Audio)
Insulin-like growth factor binding protein-3 (IGFBP-3), the product of a tumor suppressor target gene, is associated with cellular senescence and can induce apoptosis by IGF-I-dependent and -independent mechanisms. IGFBP-3 controls the bioavailability of IGFs in the extracellular environment and is known to be subject to degradation by various extracellular proteases. We show here that IGFBP-3 exists as nuclear protein in situ in human osteosarcoma tissue.Keywords: , , , ,