Day 1 :
Institute for Aging Research, Albert Einstein College of Medicine, USA
Time : 09:30-10:05
Nir Barzilai is a Chaired Professor of Medicine and Genetics and the director of the Institute for Aging Research at the Albert Einstein College of Medicine, which is currently the biggest center in the world to study the Biology of Aging, and home to 2 Centers of Excellence in the Biology of Aging. He studies healthy life span in rodents by biological interventions, and also families of centenarians and several drugs are developed based, in part, on these studies. He is a recipient of Irving S Wright Award of distinction in aging research and the IPSEN Longevity award. He is the Founder of CohBar Inc. and leading the TAME (Targeting/Taming Aging with Metformin) study multi central study to prove that concept that multi morbidities of aging can be delayed in humans and change the FDA indications to allow for next generation interventions.
Aging is the major risk for type 2 diabetes mellitus and also for cancer, Alzheimer’s and cardiovascular disease. We hypothesize that a progress in preventing these diseases will occur only if we can understand the reason people age at different rates and develop strategy to delay aging. We are intrigued as to why centenarians chronological age does not seem to match their biological age. Studying centenarians taught us that they carry genomic changes compared with people who do not survive so long. For example, they have a mutation that changes the function of the protein involved in cholesterol metabolism. Further, centenarians are also over-represented with genes that do not allow the full function of growth hormones and targeting these pathways in mice increased their health and longevity. Several of these findings have led pharmaceuticals to develop some drugs that can target specific diseases and exemplify an approach of delaying aging and several of its disease, rather than focus on one organ-specific drug at a time. To have proof of concept in humans, we chose metformin, one drug that targets the biology of aging and extends life- and health-span in animals. It is used for the treatment and to delay type 2 diabetes mellitus (T2DM), with over 60 years outstanding safety record. Metformin use is also associated with lower rates of cancer, CVD, all-cause mortality and possibly less cognitive decline. We designed the TAME (Targeting Aging with Metformin) trial, a placebo controlled, multi-center study in ~3000 elderly with a novel primary outcome of delaying the incidence of a composite of multiple age-related diseases. The study was developed in consultation with the FDA to obtain indication that would allow industry to justify the development of next-generation drugs to target aging and will further extend healthy life span in the next decade.
University of Pennsylvania, USA
Keynote: A unified pathophysiologic construct of diabetes and its complications, including malignancies, in the context of the B-cell classification of diabetes
Time : 10:05-10:40
Stanley Schwartz is an Emeritus Associate Professor of Medicine at the University of Pennsylvania. He has trained at the University of Chicago and University of Pennsylvania. He actively lectures nationally, as well as internationally, about diabetes and its treatment. He has authored numerous articles in peer-reviewed scientific journals and has been a lead or co-investigator for many clinical trials (DCCT-EDIC, LOOK AHEAD). He has created a call for minimizing hypoglycemia in hospitals using incretins, and minimizing insulin use in ‘Type 2 ‘DM. He has proposed a new classification and unified pathophysiologic construct for all diabetes. He has been elected by his peers for inclusion in Best Doctors in America® from 1996 to 2017. Though he does some research and teaches a great deal, most of his time is spent caring for patients.
We have previously presented a proposal for a new, beta-cell centric classification of diabetes based on a consilience of genetic, metabolic, and clinical research that have accrued since the current classification was instituted. It recognizes that the beta-cell is the core defect in all patients with diabetes. Differences in the genetics, insulin resistance, environment and inflammation/immune characteristics of the damage to the beta-cell in each individual will determine the phenotypic presentation of hyperglycemia and allow for a patient-centric, precision-medicine therapeutic approach, part of which we labeled ‘the Egregious Eleven’. We, now recognize the same pathophysiologic mechanisms that account for damage to the beta-cells govern the susceptibility of the cells involved in the complications of diabetes to damage by the now well-defined abnormal metabolic environment that typifies beta-cell dysfunction. This abnormal metabolic environment is typified by oxidative stress which alters metabolic pathways a la Brownlee’s Hypothesis model, alterations in gene expression, epigenetics and inflammation. This unified pathophysiologic approach to the complications of diabetes in the context of the b-cell– classification of diabetes allows us to understand the varied risk of developing complications of diabetes with similar levels of glycemic control, how non-glycemic effects of some medications for diabetes result in marked complication risk modification and the value treating co-morbidities of diabetes in effecting complication risk. We also believe that the same pathophysiologic mechanism that account for damage to the beta- cells and govern the susceptibility of the cells involved in the complications of diabetes are likely to explain the association of cancer to diabetes and obesity and explains why diabetic medications may affect cancer risk and therapy.
Medlab Clinical Ltd., Australia
Sean Hall has founded Medlab in August 2012. He has over 20 years’ experience in nutraceutical sales and development, as well as early drug discovery in Australia, Asia and the US. He has led and inspired his teams to author multiple patents, write peer reviewed articles and deliver lectures at global scientific conferences. His passion is leading his researchers into novel areas and strong commercialization opportunities. He is also an Active Member of Medicines Australia, AusBiotech, American Federation of Medical Research (AFMR), The American Academy of Anti-Ageing Medicine (A4M), World Medical Associated (WMA), Special Operations Medical Association (SOMA), and a Board Member of the International Probiotics Association (IPA).
The human intestines are colonized by a variety of bacterial phyla that with the host co-ordinate numerous metabolic processes in health and disease. As such the intestinal microbiome can positively and adversely affect end organ physiological functions (e.g., liver, skeletal muscle, adipose tissue). Several studies have shown that the gut microbiome can influence metabolic processes, such as signaling pathways, mucus secretion, immune homeostasis, cellular proliferation and maturation, metabolic regulation and stability. The nature of the human microbiome is such that it is largely dependent on dietary practices, physical activity and mode of birth. A diet rich in fermented foods and beverages likely to contain probiotic bacteria has been posited to provide health benefits. The intestinal microbiome can be adversely affected by the administration of pharmaceuticals such as antibiotics, the level of sanitation, as well as lifestyle psychological stressors. The bacteria associated with the gut microbiome undergo a natural selection through inflammatory reactions and only those that tolerate the host immune response survive where a symbiotic or parasitic relationship can be established. Medlab’s research is centered on the therapeutic/pharmacological symbiotic effects of probiotics/gut microbiome with beneficial effects on health and that gut ecology disruptions can lead to adverse outcomes to end organ physiological functions. Numerous clinical studies that have investigated the administration of probiotics and prebiotics on various disease states or conditions including antibiotic or infective diarrhea, pneumonia, various inflammatory intestinal diseases, liver disease, respiratory function, kidney function, skin conditions, allergy, joint diseases, diabetes and obesity. A plausible mechanistic and efficacious pharmacobiotic effect of probiotic bacteria is advanced. This presentation will focus on the adjuvant administration of multi-strain probiotic formulations NAFLD, T2DM and depression, utilizing specific combinations of probiotics to effect therapeutic benefit.
University of Michigan, USA
Keynote: Western-style diet, calcium supplementation and liver health: Gut microbial and metabolomic signature
Time : 11:40-12:15
James Varani has completed his PhD in Microbiology and is a Professor in the Department of Pathology at the University of Michigan. His research interest is epithelial biology and he has focused his studies on gastrointestinal health, and especially on the prevention of chronic diseases with dietary intervention.
Statement of the Problem: The Western-style diet (WSD) is strongly linked with the growing epidemic of obesity and is associated with numerous chronic age-related ailments. In the liver, specifically, non-alcoholic fatty liver disease (NAFLD) is a result. The goal of this work was to determine if dietary calcium supplementation could protect mice fed a WSD from NAFLD, including its down-stream consequences (i.e., liver fibrosis, formation of pre-cirrhotic regenerative nodules and premalignant/ malignant liver tumors).
Methods: Male C56BL/6 mice were maintained for 18-months on a WSD containing dietary calcium at either 0.41gm/Kg or 5.25gm/Kg. Livers were evaluated for steatosis, inflammation, hepatocyte degeneration, fibrosis and necrosis. A metabolomic approach was used to evaluate bile acid composition and other metabolites in bile samples, comparing mice on the WSD with and without calcium supplementation. Cecal and stool microbial communities in mice on the un-supplemented and calciumsupplemented WSD were compared using 16S rRNA gene Illumina sequencing.
Results: Steatosis was observed in most animals, irrespective of dietary calcium level. In contrast, liver inflammation and ballooning degeneration fibrosis, necrosis and incidence of regenerative hyperplastic nodules were less prevalent in mice receiving calcium. Bile acid levels were significantly higher in WSD-fed mice without calcium supplementation than in those with supplementation. Microbial populations were distinctly different on the two diets. Calcium-supplemented mice had more microbial diversity and this reflected the increased levels of several species associated with reduced inflammation and enhanced gastrointestinal barrier function. Of interest, species associated with obesity were more highly represented in mice on the un-supplemented diet, even though mice on both diets had equal weight gain over the course of study.
Conclusion: Dietary calcium supplementation can reduce NAFLD-related consequences in the context of a high-fat diet.Alterations in metabolomic profile and gut microbial populations may contribute to this effect.
University of Iceland, Iceland
Keynote: T-patterns and self-similarity from protein cities to the only large-brain mass-societies: From naked apes to string-controlled citizens
Time : 12:15-12:50
Magnus S Magnusson is a Research Professor in the University of Iceland. He has completed his PhD in 1983 from the University of Copenhagen. He is the Codirector of a DNA analysis project. He has numerous papers and invited talks at international mathematical, neuroscience, proteomics, bioinformatics and science of religion conferences and at leading universities in Europe, USA and Japan. He was the Deputy Director (1983-1988) in the Museum of Mankind, Museum of Natural History, Paris. Then, he was repeatedly invited as temporary Professor in Psychology and Ethology (biology of behavior) at the University of Paris (V, VIII & XIII). He is the Founder and Director of the Human Behavior Laboratory, University of Iceland. He formally collaborated with 32 European and American universities based on “Magnusson’s analytical model” initiated at University René Descartes Paris V, Sorbonne, in 1995.
This presentation concerns spatial and temporal self-similarity across >9 orders of magnitude, implicating a particular type of hierarchical self-similar pattern, called T-pattern, a natural (pseudo) fractal, recurring with statistically significant translation symmetry. While the self-similarity in question must have evolved from simpler to more complex, it is presented in the order discovered within a primarily ethological (biology of behavior) project concerning social interaction and organization in social insects and primates, including humans. Beginning in the 1970’s, it was partly inspired by the work of Lorenz, Von Frisch and Tinbergen for which they shared a Nobel Prize in Medicine in 1973. The smallest animals concerned were social insects and there was no implication of self-similarity. The main methodological focus of the present project has been on developing pattern definitions and detection tools. This resulted in the T-pattern, with corresponding detection algorithms and software, and their abundant detection, among others, in different kinds of human (inter-brain) interactions and later in neuronal interactions in living brains, thus showing T-patterned self-similarity of temporal interaction structure within
and between brains. Finally, unexpected spatial T-patterning in the molecular strings of DNA and proteins was noticed and consequently the realization of self-similarity in social organization, based on T-patterned (external memory) strings, more durable than the citizens, in the mass-societies of proteins and of humans – the only large-brain mass-societies. Different from the mass-societies of insects (hives) and of cells (bodies), those of, respectively, protein and human mass-societies relying extensively on external T-patterned strings, respectively, DNA and the very recent strings, called texts, including those thoroughly standardized, copied, distributed, promoted and enforced, called legal or holy texts. With human and protein citizens specialized on the basis of durable external T-patterned strings and with some citizens, for example, moving (even walking) along tracks and doing meaningful work, a new definition of what is alive seems justified. Thus, proteomics may provide new insights and ideas for a bio-social science and vice-versa.