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.
Adenylyl cyclase inhibition enhances proliferation of senescent cells and promotes wound healing of aged rats
One of the cardinal characteristics of senescent cells is hypo-responsiveness to growth factor stimuli. However, we previously observed that some G protein-coupled receptor agonists, such as lysophosphatidic acid (LPA), stimulate mitogenic activation in senescent cells to some degree, while receptor tyrosine kinase agonists block mitogenic activation. Treatment with ACI reduced the basal and LPA-induced cAMP levels both in young and senescent cells, and enhanced basal and LPA-induced DNA synthesis, and proliferation and migration of senescent cells.Keywords: Wound healing, LPA, ACI, dbcAMP, PCNA
The endoecological(intersticial)crisis and immune deficiency increase the risk for development of inflammatory, degenerative, oncological processes and become the grain for development of specific pathological processes and early aging. Clinico-instrumental examination of 87 patients with various visceral organ diseases allows us to indicate the criteria of poor (retrograde) lymph flow, phenotypic markers of genotypic programs.Keywords: lymphatic disorders, phenotypic markers of genotypic programs, , ,
The SENS Foundation Research Center has been engaged in interdisciplinary research aimed at repairing aging cells and macromolecules since its inception in spring 2008. We discovered enzymes degrading indigestible "junk" molecules such as lipofuscin and oxysterols. We combine this with work in lysosomal enzyme replacement therapy to develop drug delivery systems that get these enzymes to the organelle affected by junk accumulation in vitro and in vivo. We also began work to remove senescent t-lymphocytes from aged mice.Keywords: SENS, lipofuscin, A2E, oxysterols, immunosenescence
The age pigment lipofuscin is thought to be a key player in age-related declines seen in most organisms, especially humans. We are experimenting with the use of pulsed lasers to selectively destroy lipofuscin granules in aging cells, thereby ridding them of this key roadblock to efficient recycling via autophagy. Existing treatments using selective photothermolysis to destroy pigments are very harsh; near-instantaneous vaporization of pigment granules results in large cavitation bubbles which literally blow apart the treated cell.Keywords: selective photothermolysis, lipofuscin, laser, autophagy,
Organiser's Note: The presenter of this talk withheld their permission for video to be published.Keywords: Ovary, oocyte, aneuploidy, aging, caloric restriction
Naked mole-rat cells are hypersensitive to contact inhibition - a clue to extraordinary cancer resistance
The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Our previous studies suggested that small-bodied, long-lived mammals evolve novel anticancer mechanisms. However, the nature of these mechanisms was unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed "early contact inhibition".Keywords: Naked mole-rat, cancer, contact inhibition, longevity,
Organiser's Note: The presenter of this talk withheld their permission for video to be published.Keywords: Sirt1, transgenic, resveratrol, cancer, aging
Legal and regulatory frameworks govern the entire innovation trajectory in life extension from original research, the conduct of clinical trials, to granting of marketing authorisation and financial considerations. As medical science and the structure of the industry evolves, the regulatory and legal regimes of the past are often found in need of reform.Keywords: regenerative medicine, law, regulation, advanced therapies, intellectual property
To measure strategies for adjustment of the aged subjects, some truly effective measures to postpone and treat human ageing in urban society, by tackling it as an engineering problem. An objective test consists of 34 items; each item contains a statement representing a problematic situation relating to home, health, emotional life or social life of the subject along with four alternative responses. The responses represent four alternative strategies of adjustment i.e. intrapersistive approach mode, extra pursistive approach mode, punitive avoidance mode and defensive avoidance mode.Keywords: intrapersistive approach mode, extra pursistive approach mode, punitive avoidance mode, defensive avoidance mode,
Long-term Treatment with a "Yang- invigorating" Chinese Herbal Formula, Wu-Zi-Yan-Zong-Wan, Reduces Mortality and Liver Oxidative Damage in Chronic Alcohol Intoxicated Rats
Long-term alcohol consumption has been reported to increase oxidative stress in multiple organs and accelerate the aging process. A previous study in our laboratory has shown that Wu-Zi-Yan-Zong-Wan (WZ), a "Yang- invigorating" Chinese herbal formula, protected against ethanol-induced toxicity in HepG2 cells transfected to express human CYP2E1, presumably by enhancing mitochondrial antioxidant status and functional ability. The present study aims to investigate whether WZ extract treatment can afford hepatoprotection against ethanol toxicity in rats.Keywords: Chinese herbal formula, ethanol toxicity, liver damage, oxidative stress,
Recently a concept was developed assuming that senescence is programmed by genome, being the last step of ontogenesis. It was also suggested that senescence was invented by biological evolution to accelerate this evolution. A consequence of such kind of reasoning consists in that for human senescence should be regarded as an atavism since humans do not rely on their evolution which is too slow. If senescence is programmed, it might be prevented by inhibition of this program just as inhibition of the programmed cell death (apoptosis) is shown to prevent apoptosis.Keywords: mitochondria, antioxidant, senescence, programmed aging,
Among the 82 published studies which test compounds for their effects on the longevity of healthy, long-lived rodents (mice, rats, and Guinea pigs), only 2 report both lifespan extension and food consumption, thereby excluding a caloric restriction (CR) confound. Six other studies report lifespan extension without a significant change in body weight. However, body weight is an unreliable surrogate measure of caloric consumption. The remainder of the studies also contain serious confounds.Keywords: Longevity therapeutic, caloric restriction, lifespan assays, longevity, rodent
Inducing pluripotency in somatic tissue cells has emerged as a promising approach to study cellular reprogramming and to generate cells that may be useful in regenerative medicine. Direct reprogramming of somatic cells to pluripotency state is possible through transduction and consequently integration in the genome of a selected group of transcription factors. However, viral integration of the required transcription factors may result in tumorgenicity and other drawbacks.Keywords: reprogramming, aging, pluripotency, ,
Progressive regenerative medicine and anti-aging medicine is defined as the earliest detection, intervention and prevention of age related diseases. The current standard of care only requires doctors to do evaluations of patients musculoskeletal systems when the patients present with signs and symptoms.
In this presentation I will demonstrate that the earliest detection of musculoskeletal conditions such as degenerative arthritis can be achieved far sooner than the onset of the traditional signs and symptoms practiced in disease based medicine.Keywords: arthritis, arch, foot, elastic, recoil
The oldest polymerase domains involved in telomere repeats diversity are currently HCHLHCC and IHCP, showing RDRPs diverging into RTs. Prokaryotic AAAAAAAA (RNAs) have evolved to TTTTTTTT (DNAs), which eventually evolved into the eukaryotic TTTTTTTT-TTTTGGGG-TTTTAGGG-TTTAGGG-TTAGGG-TTAGG telomere direction. This telomere evolution direction matches with the rDNA based tree of life running in parallel with the polyphyletic polymerase evolution.Keywords: t-loop deletion factor, HCHLHCC, IHCP, telomere/s, blunt ends
All polymerases together are the main factor for the diversity of telomere repeats. Telomerases have major role in telomere repeats diversity, as extending telomeres via RNA primers. All having unique conserved nucleotides region/s within each RT, which are not found in any other polymerases.
DNA end replication problem is known to come from the RNA primer loss factor. Here an additional DNA end problem factor has been suggested as DNA blunt ends reduction from homologous proteins, during the t-loop formation.Keywords: telomeres, aging, blunt ends, resolvase, relaxase
The National Institute on Aging Interventions Testing Program (ITP) was developed to: 1) provide a standardized program for preclinical evaluation of the efficacy of interventions aimed at prolonging health-span and/or life-span; 2) to provide the NIA with a mechanism to evaluate possible health dangers of purported, but untested, "anti-aging" treatments; 3) candidate treatments emerging from these preclinical studies can then be recommended for clinical evaluation.Keywords: mortality risk, dietary intervention , , ,
Irreversible differentiation (change of morphogenetic status) and programmed death (apoptosis) are observed only in somatic cells. Cell division is the only way by which the morphogenetic status of the offspring cells may be modified. It is known that there is a fixed limit to the number of possible cell divisions, the so-called 'Hayflick limit'. Existing links between cell division, differentiation and apoptosis make it possible to conclude that all these processes could be controlled by a single self-reproducing structure.Keywords: DNA, RNA, centtriole, differentiation, aging
Bone marrow stem cells (SCs) can be mobilized into blood circulation, depending on chemoattractive bone marrow environments, and contribute to tissue regeneration. Aging and different diet conditions may modify the regenerative capacity of the animals and concomitantly their lifespan.Keywords: Caloric Restriction, High Fat Diet, Stem Cell, Aging,
Senescence of retinal pigment epithelial cells is a crucial event in the pathogenesis of age-related macular degeneration. In the current report human ARPE-19 cells subjected to recurring oxidative stress were used as an in vitro model of premature senescence and we focused on quantitative proteomic analysis of partially degraded proteins. Our quantitative approach is based on the use of light (non-deuterated) and heavy (deuterated) acrylamide to alkylate cysteine residues in proteins.Keywords: retinal pigment epithelial, waste accumulation, quantitative proteomics, ,
Parental longevity impacts on the healthy ageing of their offspring: Effects on blood and clinical chemistry parameters in centenarians' offspring
Around the 60's in all the industrialized countries the progressive decline of the mortality (1-2% year) in individuals over-80 years old has risen up of about twenty times the number of oldest old people. Ageing is a general phenomenon which rate is increasing slowing and in order to understand and study age related disease we have taken as a model centenarians and their offsprings.Keywords: Ageing, immunoglobulin, offsprings, clinical chemistry parameters,
Yeast, plants, worms and flies use a methyltransferase to metabolize age-damaged (R,S)AdoMet, but what do mammals do?
Organiser's Note: The presenter of this talk withheld their permission for video to be published.
While the ability to break down a wide variety of molecules for energy confers a distinct evolutionary advantage to lower organisms, this is not necessarily the case as organisms become more complex. As a result, molecules that can easily be broken down by microorganisms but not higher ones could potentially accumulate in these higher organisms as they age. This may in fact be the case with the biological methyl donor S-adenosyl-L-methionine (AdoMet).Keywords: Age-damaged AdoMet, Yeast, Methyltransferases, Diastereoisomers,
Diverse hostile Earth's/Space extreme natural (and manmade) environments including particularly life-threatening ones - Himalaya and other highest altitude mountains systems climbing; Arctic, Antarctic and Karakum desert expeditions; solitary sailing across the oceans; high exposure to different kinds of space and terrestrial radiation, etc - represent various aspects of Earth's extreme primordial conditions (extreme hypoxia, radiation, cold, heat, redox (free-radical) attack "stresses", etc, which have been primordial terrestrial and extraterrestrial background, archetypal environment-biotKeywords: physiological ambivalence and complementarity of free radicals, redoxomics, , ,
Drugdiscovery@home - a new distributed computing platform for in silico drug discovery in the fields of aging, stem cells and cancer.
The volunteer computing projects give significant computational resources for the researchers, which can be an important asset for the fields of research, dependent on computational performance. DrugDiscovery@Home is the first distributed computing project devoted to the fields of aging and regenerative medicine.
In our project we use two main methods - molecular dynamics and flexible docking. These software applications are used for the protein structure refinement and for the early in silico discovery of biologically active compounds.Keywords: volunteer computing, boinc, stem niche
The group of Wnt signaling pathways plays significant role in regulation of adult stem cells activities. The balance between canonic and non-canonic Wnt pathways exerts a serious influence on the balance between stem cells self-renewal and differentiation in adult stem niches.Keywords: beta amyloid, stem cells, molecular modelling, ,
It is well established that dietary restriction (DR) reduces the pathology and disease associated with ageing while increases survival in rodents, worms, flies and yeast. The molecular and cellular events underlying these various outcomes are currently unclear. So far, the alteration of cellular senescence by DR has not been explored. Recently we found that frequencies of senescent cells and cellular oxidative damage increase with age in various tissues of mice, including liver and intestine. Therefore, we tested whether DR has an effect on cellular senescence in adult mice.Keywords: cellular senescence, dietary restriction, , ,
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: , , , ,
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
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
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
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
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
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, , , ,
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: , , , ,