SYMPOSIUM PROGRAM BOOK

Addressing the Drivers of Frailty: Active Nutrients for Mitochondrial Health, Bioenergetics and Functionality

SYMPOSIUM PROGRAM BOOK

12-13.30h

September

26th

Session of the 15th EuGMS CongressVenue: Room 4 ICE Congress Center - Krakow, Poland

LUNCH SYMPOSIUM

Welcome & Introduction Chair: Jürgen M. Bauer, Germany

Nutritional strategies to compensate for the anabolic resistance of aging Luc J. C. van Loon, The Netherlands

Targeting muscle mitochondrial bioenergetics in sarcopeniaJerome N. Feige, Switzerland

Reversing age-related mitochondrial dysfunction, insulin resistance and functional decline: The role of glutathione and a novel nutritional approach Rajagopal V. Sekhar, USA


Venue: Room 4 ICE Congress Center - Krakow, Poland

CHAIRMAN BIOGRAPHY:In September 2016 Juergen M. Bauer took over the newly established chair for geriatric medicine at the Ruprecht Karls University of Heidelberg, Germany. He is also director of the Network Aging Research in Heidelberg and of the Agaplesion Bethanien Hospital Heidelberg. In 2010 he had been appointed director of the newly formed Centre for Geriatric Medicine Oldenburg, Germany, which is an integral part of the medical campus of the Carl von Ossietzky University Oldenburg. Between 2004 and 2010 he worked as assistant medical director at the Department of Geriatric Medicine at the University of Erlangen-Nuremberg, Germany. Before moving into the field of geriatric medicine Juergen M. Bauer was trained in gastroenterology and as a specialist in clinical nutrition. In recent years, Juergen M. Bauer’s research interest has focused on nutrition and its relationship with functionality in older persons. He has been a member of several international expert groups that worked on the definitions of sarcopenia and frailty in older persons.

Juergen M. Bauer is a member of several national and international medical societies. In 2010 he was honored to become a member of the European Society for Clinical Nutrition and Metabolism (ESPEN) faculty. He is also a member of the committee of scientific advisors of the International Osteoporosis Foundation (IOF). From 2007 until 2015 he was a member of the executive board of the European Geriatric Medicine Society (EuGMS) and was the congress president of the EuGMS Congress 2018, which was held in Berlin. Juergen M. Bauer serves currently as the immediate past-president of the German Society for Geriatric Medicine (DGG). In recent years Juergen M. Bauer has been working as a co-editor of Clinical Nutrition and of the German Journal of Gerontology and Geriatrics, and since 2016 as section editor of Current Opinion in Clinical Nutrition and Metabolic Care.

INTRODUCTORY PARAGRAPH:Frailty imposes a major healthcare risk on those that are a�ected by this geriatric syndrome. Its prevalence increases significantly with age. Its prevention and therapy has been regarded as one of the major challenges to the healthcare sectors of our rapidly aging societies. Geriatricians, general practitioners and specialists from other disciplines as well have to take up this challenge by identifying those that are at risk and by taking appropriate measures, if indicated. At present, there is no pharmaceutical agent that could cure or prevent frailty. It also has to be appreciated that older patients, especially those that are frail, constitute an extremely vulnerable population that is a�ected by side e�ects of drugs more seriously than younger or non-frail individuals. Preventive and therapeutic measures in frail patients should therefore not cause additional risks, but they should be extremely safe. Specifically tailored physical therapy and targeted nutritional interventions fulfill these prerequisites to the currently greatest possible extent. Over the last few years, new scientific evidence has accumulated, which indicates that clinical nutrition may reach far beyond the task to simply meet standard requirements in older persons. Several novel approaches are highly promising at the moment and recent evidence will be presented in this symposium by internationally acclaimed experts in their fields of research. Let us have a first look at the future of frailty therapy!

Jürgen M. Bauer, MD

Welcome & Introduction


SPEAKER BIOGRAPHYLuc van Loon is a Professor of Physiology of Exercise at the Department of Human Biology at Maastricht University Medical Centre. Luc has an international research standing in the area of skeletal muscle metabolism. Current research in his laboratory focuses on the skeletal muscle adaptive response to exercise, and the impact of nutritional and pharmacological interventions to modulate muscle metabolism in health and disease. The main research interests of his laboratory include muscle metabolism, sports nutrition, clinical nutrition, adaptation to endurance and resistance type exercise, and the use of physical activity and/or nutritional interventions to improve health in chronic metabolic disease and aging. The latter are investigated on a whole-body, tissue, and cellular level, with skeletal muscle as the main tissue of interest.

The research group has authored more than 340 original, peer-reviewed research and review articles. Luc is a member of the Editorial Board of the International Journal of Sport Nutrition and Exercise Metabolism (IJSNEM) and the European Journal of Sport Science (EJSS) and the Scientific Board of the European College of Sport Science (ECSS). To support the use of stable isotopes in biomedical research, Luc is also scientific coordinator of the Stable Isotope Research Centre (SIRC) at Maastricht University Medical Centre.

KEY MESSAGES:Skeletal muscle protein is constantly being synthesized and broken down, with a turnover rate of about 1-2% per day. The rate of skeletal muscle protein synthesis is regulated by two main metabolic stimuli, food intake and physical activity. Food intake, or more specifically protein ingestion, directly elevates muscle protein synthesis rates. The dietary protein derived essential amino acids act as signaling molecules activating anabolic pathways and provide precursors for muscle protein synthesis. Ingestion of a meal-like amount of dietary protein elevates muscle protein synthesis rates for several hours, providing evidence that ‘you are what you just ate’. Post-prandial protein handling and, therefore, the post-prandial muscle protein synthetic response to protein ingestion is modulated by numerous variables, including the amount, type and composition of the protein ingested, as well as the matrix of the food through which the protein is provided. Furthermore, non-food factors such as mastication, body position, habitual protein intake, and body composition are all factors that can largely impact post-prandial protein handling. When food is ingested after a bout of physical activity the post-prandial muscle protein synthetic response is augmented, with higher muscle protein synthesis rates sustained over a more prolonged period of time. In other words, when you ingest protein following a bout of physical activity ‘you become even more of what you just ate’. In contrast, when protein is ingested following a period of inactivity the post-prandial muscle protein synthetic response is blunted, coined anabolic resistance. Therefore, disuse makes you ‘become less of what you just ate’. These concepts play a key role in the prevention and management of sarcopenia.

Prof. Luc J. C. van Loon

Nutritional strategies to compensate for the anabolic resistance of aging

SPEAKER BIOGRAPHYDr Jerome N. Feige is the head of the Musculo-Skeletal department of Nestlé Research in Lausanne, Switzerland, and a recognized expert in muscle and aging biology. He holds a degree in Bioengineering and a PhD in Biology from the University of Lausanne. Dr Feige performed post-doctoral research at the Institute of Genetics, and Molecular and Cellular Biology in Strasbourg, France on the molecular regulation of energy metabolism. He subsequently worked as laboratory head at the Novartis Institute of Biomedical Research in Basel, Switzerland, where he performed drug discovery for muscle diseases and contributed to the development of new therapies currently in late stage clinical testing. Since 2012, Dr Feige has held increasing responsibilities in the Nestlé Institute of Health Sciences where he established a research program studying muscle biology and a translational department developing nutritional therapies to support the Musculo-Skeletal system. Dr Feige is also an adjunct lecturer at the Ecole Polytechnique Fédérale de Lausanne (EPFL) where he teaches nutrition and biology, and trains PhD students in biomedical science.

KEY MESSAGES:Controlling the physiological decline of tissues and cellular processes during aging is central to maintaining healthspan and quality of life in senior people. Sarcopenia is the age-related loss of muscle mass and function, which directly contributes to physical disability, loss of independence and mortality in the older population. In the Multi-Ethnic Molecular determinants of Sarcopenia (MEMOSA) study, we studied the mechanisms that discriminate sarcopenia from healthy aging in a multi-centric study across di�erent ethnicities. Individuals with sarcopenia reproducibly demonstrated a prominent transcriptional and functional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, which parallels a decline in NAD+ levels. These results point to mitochondrial homeostasis as a key mediator of pathological muscle decline during aging and specific nutritional solutions targeting mitochondria will be discussed to recover the functional capacity of sarcopenic muscle.

Dr. Jerome N. Feige

Targeting muscle mitochondrial bioenergetics in sarcopenia

SPEAKER BIOGRAPHYRajagopal V Sekhar MD is Associate Professor of Medicine in the Section of Endocrinology, Diabetes and Metabolism at Baylor College of Medicine in Houston, TX (USA). He is a Clinical Endocrinologist by training, and also has an active research program and heads a translational lab at Baylor. Dr. Sekhar is a recognized expert in energy and nutrient metabolism, and is focused on understanding mechanisms contributing to abnormalities in mitochondrial fuel and energy metabolism, insulin resistance, muscle weakness, cognitive decline, sarcopenia and obesity as seen in geriatric aging, premature aging in HIV, cognitive decline in aging and Alzheimer’s disease, and diabetes. Over the past 2 decades he has investigated deficiency of glutathione (the most abundant endogenous antioxidant protein) and identified reversible mechanisms via studies in humans and basic science. He also made the exciting discovery that Glutathione adequacy is critically necessary for optimal mitochondrial function, and can improve mitochondrial defects in humans. He has completed 2 open label clinical trials and an NIH-funded randomized clinical trial and results are expected shortly. Dr. Sekhar’s work has implications for mitochondrial and metabolic health, inflammation, insulin resistance, physical strength, exercise capacity, cognition and body composition (including sarcopenic obesity). He is the Principal Investigator on an ongoing NIH-funded randomized clinical trial in Alzheimer’s disease, and other translational studies in intermediary metabolism and novel nutritional strategies.

KEY MESSAGES:Oxidative stress and mitochondrial dysfunction are believed to drive the aging process, and interventions to reverse these in humans are limited. Aging is also associated with insulin resistance, inflammation, declining strength and elevated body fat for which mechanisms are not well understood and interventions are lacking. Via complementary translational studies in aged rodents and older humans, my group discovered that deficiency of the most abundant endogenous intracellular protein glutathione could play a key role in these defects. Glutathione deficiency occurred due to diminished availability of its precursor amino acids glycine and cysteine (but not glutamic acid), and can be corrected with supplemental GlyNAC (combination of glycine plus cysteine provided as N-acetylcysteine). We found that glutathione deficiency results in mitochondrial dysfunction, and that reversing glutathione deficiency leads to recovery of impaired mitochondrial fuel oxidation, and lowers oxidative stress to impact insulin resistance and body composition in aging. We also found that glutathione deficiency appears to predispose to accelerated aging as seen in HIV patients with mitochondrial dysfunction, oxidative stress, insulin resistance, muscle weakness and inflammation, and that supplementing GlyNAC can improve/reverse these defects. Our discoveries could have profound implications for improving the health of the aging population, and could lead to a transformational change in the care of older people.

Dr. Rajagopal V. Sekhar

Reversing age-related mitochondrial dysfunction, insulin resistance and functional decline:

The role of glutathione and a novel nutritional approach

The Nestlé Nutrition Institute (NNI) is a non for profit association based in Vevey, Switzerland, that shares leading science-based information and education with healthcare professionals, scientists and nutrition communities and stakeholders in all parts of the world through various forms of interaction. The Institute was established in 1981 with the goal to foster “Science for Better Nutrition” to help enhance the quality of people’s lives all over the world

ACCESS PUBLICATIONS, EDUCATIONAL VIDEOS & SCREENING TOOLSOur nutrition videos are lectures recorded at global nutrition conferences and workshops, featuring leading experts addressing a wide range of key nutritional topics. These webinars are freely available to Nestlé Nutrition Institute members, and cover all the most-discussed subjects in nutrition today.

LEARN MORE ABOUT AGE-ASSOCIATED CELLULAR DECLINE (AACD) & HOW IT MAY BE MANAGEDEvidence has emerged on the cellular changes and mitochondrial dysfunction that generally occur with age or the onset of medical conditions, and novel cellular nutrients able to act on these metabolic pathways important for energy and vitality, strength and stamina, and protection.

ACCESS RECORDED LECTURES:Reversing mitochondrial dysfunction and improving metabolic health in older humans and HIV patients: A translational journey Dr. Rajagopal V Sekhar - Associate Professor of Medicine-Endocrinology at Baylor College of Medicine [Houston, US]

View Webinar: https://www.nestlenutrition-institute.org/resources/videos/details/reversing-mitochondrial-dysfunction-and-improving-metabolic-health-in-older-humans-and-hiv-patients-a-translational-journey

Age-associated cellular decline Dr. Matteo Cesari - Associate Professor of Geriatrics at the Università di Milano and Head of the Geriatric Unit at

the Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy].

View Webinar: https://portal.klewel.com/watch/webcast/wRzbzmSeEcrNegVggfyVxb/talk/1

ACCESS ONLINE PUBLICATIONS: Sekhar, RV. (2019). Oxidation damage accumulation aging theory (The novel role of glutathione). In D Gu & ME Dupre (Eds.), Encyclopedia of gerontology and population aging. Springer Nature Switzerland AG.

View Publication: https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-69892-2_51-1

Sekhar, RV. (2019). Human aging, mitochondrial and metabolic defects (The novel protective role of glutathione). In D Gu & ME Dupre (Eds.), Encyclopedia of gerontology and population aging. Springer Nature Switzerland AG.

View Publication: https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-69892-2_45-1

Andreux PA, et al. Mitochondrial function is impaired in the skeletal muscle of pre-frail elderly. Sci Rep. 2018; 8: 8548. Published online 2018 Jun 4. doi: 10.1038/s41598-018-26944-x.

View Publication: https://www.nature.com/articles/s41598-018-26944-x

Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. doi: 10.1038/s41467-018-03421-7.

View Publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876407/

ACCESS EXPERT INTERVIEWS:The potential for special nutrient intervention to normalize glutathione levels and support cellular health.Dr. Rajagopal V Sekhar - Associate Professor of Medicine-Endocrinology at Baylor College of Medicine [Houston, US]

View Video: https://www.youtube.com/watch?v=X2425Wb0FVY&t=5s

Role of mitochondrial dysfunction in age-associated cellular decline: Mechanisms and perspectives Dr. Matteo Cesari - Associate Professor of Geriatrics at the Università di Milano and Head of the Geriatric Unit at the Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy]

View Video: https://www.youtube.com/watch?v=x9G2o-SW0uk

www.nestlenutrition-institute.org

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SYMPOSIUM PROGRAM BOOK