Aging and Nutrition: Novel Approaches and Techniques

Aging and Nutrition: Novel Approaches and Techniques

Friday, December 2, 2016

The New York Academy of Sciences

Several interventions have been identified that significantly extend healthy lifespan in mammals. Caloric restriction, for example, has been shown to improve healthspan in a variety of organisms, including rodents. Conversely, animals fed a diet with a normal caloric content, but with limiting amounts of the essential amino acid methionine, are up to 45% longer-lived than control animals. These and many other studies collectively demonstrate that alterations in nutrition and metabolism can have profound effects on healthy aging.

While studies are ongoing using conventional and established approaches to explore the molecular mechanisms underlying healthspan-extending interventions, many powerful new techniques are also being developed (e.g. genome engineering, high-throughput sequencing, DNA methylomics) that can be used to great effect for studies of healthy aging.

To explore the interplay between aging, nutrition, and metabolism, as well as the important role that novel technologies will play in current and future studies, The Orentreich Foundation for the Advancement of Science, Inc. and The Sackler Institute for Nutrition Science at the New York Academy of Sciences are bringing together several preeminent researchers in these fields.

Attendance for this event is limited in order to facilitate high level discussions and interactions.

Registration Closed

This event will be available on Livestream at: https://livestream.com/newyorkacademyofsciences/agingnutrition2016

Agenda

* Presentation times are subject to change.


Friday, December 2, 2016

12:30 PM

Registration

1:00 PM

Welcoming Remarks
David S. Orentreich, MD, Orentreich Foundation for the Advancement of Science, Inc.
Ellis Rubinstein, The New York Academy of Sciences

Session 1: Nutrition, Metabolism and Healthy Aging

Facilitated by: Lenore Launer, PhD, National Institute of Aging

1:15 PM

Effect of Early Dietary Restriction on DNA Methylation
Arlan Richardson, PhD, University of Oklahoma Health Sciences Center

1:40 PM

Translational Geroscience: Teaching Old Dogs New Tricks
Matt Kaeberlein, PhD, University of Washington

2:05 PM

Mechanisms of Longevity in Long-lived Mammals
Vera Gorbunova, PhD, University of Rochester

2:30 PM

Session 1 Panel and Q&A

3:00 PM

Networking Coffee Break

Session 2: Novel Approaches to Healthy Aging Studies

Facilitated by: Jay Johnson, PhD, Orentreich Foundation for the Advancement of Science, Inc.

3:30 PM

Linking Molecular Interventions to Systemic Outcomes in Aging
Nicholas Stroustrup, PhD, Harvard University

3:55 PM

Comparative Genomics of Lifespan Control
Vadim Gladyshev, PhD, Brigham and Women's Hospital, Harvard Medical School

4:20 PM

Senescent Cell Elimination as a Means to Slow Aging and Disease
Jan van Deursen, PhD, Mayo Clinic

4:45 PM

Session 2 Panel and Q&A

5:15 PM

Closing Remarks
Gene Ables, PhD, Orentreich Foundation for the Advancement of Science, Inc.
Gilles Bergeron, PhD, The Sackler Institute for Nutrition Science

5:30 PM

Networking Reception

6:30 PM

Conference Adjourns

Organizers

Gene Ables, PhD

Associate Science Director, The Orentreich Foundation for the Advancement of Science, Inc.

Dr. Ables received his degree of Doctor of Veterinary Medicine from the University of the Philippines. He then obtained his PhD from Hokkaido University (Japan). His post-doctoral research in Preventive Medicine and Nutrition at Columbia University focused on liver lipid metabolism. In 2006, he was appointed Associate Research Scientist at the Columbia University Medical Center. Dr. Ables joined OFAS in April 2011 as a Senior Scientist. Recently appointed Associate Science Director, he leads staff in investigations of the methionine-restricted diet's effects on metabolism, cancer, and epigenetics.

Gilles Bergeron, PhD

Executive Director, The Sackler Institute for Nutrition Science

Dr. Gilles Bergeron has worked in international nutrition for more than 25 years. He has extensive experience in nutrition in the life cycle, food security, agriculture/nutrition linkages and monitoring and evaluation. A founding member and Deputy Director of the Food and Nutrition Technical Assistance (FANTA) project, he spent 18 years overseeing FANTA's work in policies and programs; nutrition and infectious diseases; maternal and child nutrition; agriculture/nutrition linkages and emergency nutrition response. Prior to joining FANTA, he spent 6 years as Research Fellow with the International Food Policy Research Institute (IFPRI) and 3 years with the Institute of Nutrition for Central America and Panama (INCAP) in Guatemala. He has operated in Africa, Latin America and Asia, and his work has been published in leading scientific journals such as The Lancet, Advances in Nutrition, World Development, The Journal of Development Studies, and Food and Nutrition Bulletin. He received his PhD in development sociology from Cornell University in 1994.

Jay Johnson, PhD

Senior Scientist, The Orentreich Foundation for the Advancement of Science, Inc.

Dr. Johnson received his doctorate in Molecular Biology from Case Western Reserve University (Cleveland, OH). His post-doctoral work at Fox Chase Cancer Center (Philadelphia, PA) used a liposarcoma model system to investigate the maintenance of telomeres, important nucleoprotein structures with roles in aging and cancer. Dr. Johnson then joined the University of Pennsylvania (Philadelphia), where his early work explored cellular defects in patients with Werner and Bloom's syndromes, genetic diseases characterized by accelerated aging and cancer predisposition. Dr. Johnson's recent work has focused on exploring the mechanistic basis of the benefits of methionine restriction in S. cerevisiae and cultured mouse and human cells.

Mireille Mclean, MA, MPH

Director, The Sackler Institute for Nutrition Science

Mireille Seneclauze Mclean joined the Sackler Institute for Nutrition Science at the New York Academy of Sciences in 2011 as a Program Manager and was later promoted to Director. Her activities include managing the growing pool of research grants issued through the Sackler Institute's Research Funds, organizing multidisciplinary workshops and symposia in the field of nutrition, and supporting the dissemination of research. Prior to this, she spent over 10 years doing fieldwork for several international NGOs intervening in crisis situations. She holds an MA in Development Economics and International Development from the University of Sussex and a Master of Public Health from the Liverpool Faculty of Medicine.

George Church, PhD

Professor, Department of Genetics, Harvard Medical School

George Church is a Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard, and the Massachusetts Institute of Technology (MIT). He is Director of the U.S. Department of Energy Center on Bioenergy at Harvard and MIT and Director of the National Institutes of Health Center of Excellence in Genomic Science at Harvard.

George is widely recognized for his innovative contributions to genomic science and his many pioneering contributions to chemistry and biomedicine. In 1984, he developed the first direct genomic sequencing method, which resulted in the first commercial genome sequence (the human pathogen, H. pylori). He helped initiate the Human Genome Project in 1984 and the Personal Genome Project in 2005. George invented the broadly applied concepts of molecular multiplexing and tags, homologous recombination methods, and array DNA synthesizers.

Lenore Launer, PhD

Senior Investigator, National Institute on Aging, National Institutes of Health

Dr. Launer is a Senior Scientist and Chief of Neuroepidemiology Section in the Intramural Research Program at NIA. She directs a suite of prospective, community-based cohorts, which provide a virtual life-course study of risk factors and early biomarkers for, and consequences of brain aging. Specific research interests include the role of microvascular disease, cerebral changes in physiologic functioning, and cardio-vascular risk factors as they are studied in observational cohorts and incorporated into prevention trials.

Speakers

Jan van Deursen, PhD

The Mayo Clinic

Dr. van Deursen received his PhD in Cell Biology at the University of Nijmegen and is currently a Professor of Biochemistry, Molecular Biology and Pediatrics at Mayo Clinic. He is the Vita Valley Professor of Cellular Senescence and Director of the Senescence Program in the Robert and Arlene Kogod Center on Aging.

The aging related work of the van Deursen lab focuses on the progeroid gene BubR1, which encodes a core component of the mitotic checkpoint whose level of expression markedly declines with aging. About 10 years ago, the lab discovered that BubR1 hypomorphic mice that begin life with low amounts of the mitotic checkpoint protein, BubR1, die early and develop multiple progeroid and age-related disorders. Shortly thereafter, others demonstrated that loss of function mutations in BubR1 cause mosaic-variegated aneuploidy, a human syndrome that is characterized by aneuploidy, cancer predisposition and several progeroid traits. These observations led to the idea that depletion of BubR1 with age is a key determinant of longevity and age-related disorders. His lab went on to test this hypothesis using BubR1 transgenic mice in which age-related decline of BubR1 is prevented. These mice are resistant to tumorigenesis, have an extended lifespan and delayed age-related decline in several tissues and organs important to human health in the absence of any overt negative side effects. These findings identify BubR1 and its regulator(s) as therapeutic targets for treatment of a broad spectrum of human cancers and key age-related disorders that dictate health- and lifespan.

In addition, using the BubR1 progeroid model, the van Deursen lab was the first to show an in vivo link between p16-induced cellular senescence and the development of age-related pathologies. Then, in collaboration with several laboratories in the Kogod Center on Aging, including the Kirkland and the LeBrasseur labs, his lab went on to show that clearance of p16-positive senescent cells from BubR1 progeroid mice delays the onset of age-related disease, further confirming the causal link between senescence and aging and demonstrating that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.

Vadim Gladyshev, PhD

Brigham and Women's Hospital, Harvard Medical School

Dr. Vadim N. Gladyshev is a Professor of Medicine at Brigham and Women's Hospital, Harvard Medical School, Director of the Center for Redox Medicine, and Associate Member of the Broad Institute. He graduated (1988) and received his PhD (1992) from Moscow State University, Russia, followed by postdoctoral training at NIH. In 1998, he joined the University of Nebraska faculty, where he became a Charles Bessey Professor of Biochemistry in 2005 and the Director of the Redox Biology Center in 2007. Since 2009, he has been at the Brigham and Women's Hospital, Harvard Medical School. Dr. Gladyshev works in the areas of micronutrients and redox biology as applied to aging and cancer. He has a longterm interest in the mechanisms of aging and regulation of lifespan. His research uses a variety of model organisms and applies high-throughput approaches to achieve systems level understanding of aging. Dr. Gladyshev has published approximately 300 articles and elected as an AAAS fellow. He is a recipient of the NIH Eureka, Merit, and most recently the NIH Director's Pioneer Award to study mechanisms of lifespan control.

Vera Gorbunova, PhD

University of Rochester

Vera Gorbunova is a Professor of Biology at the University of Rochester and a co-director of the Rochester Aging Research Institute. Her research is focused on understanding the mechanisms of longevity and genome stability and on the studies of exceptionally long-lived mammals. Dr. Gorbunova earned her BSc degrees at Saint Petersburg State University, Russia and her PhD at the Weizmann Institute of Science, Israel. Dr. Gorbunova pioneered comparative biology approach to study aging and identified rules that control evolution of tumor suppressor mechanisms depending on the species lifespan and body mass. Dr. Gorbunova also investigates the role of Sirtuin proteins in maintaining genome stability. More recently the focus of her research has been on the longestlived rodent species the naked mole rats and the blind mole rat. Dr. Gorbunova identified high molecular weight hyaluronan as the key mediator of cancerresistance in the naked mole rat. Dr. Gorbunova has over 60 research papers including publications in Nature and Science. Her work received awards of from the Ellison Medical Foundation, the Glenn Foundation, American Federation for Aging Research, and from the National Institutes of Health. Her work on cancerresistance in the naked mole rat was awarded the Cozzarelli Prize from PNAS for outstanding scientific excellence and originality. Most recently she was awarded a prize for research on aging from ADPS/Alianz, France, Prince Hitachi Prize in Comparative Oncology, Japan, and Davey prize from Wilmot Cancer Center.

Matt Kaeberlein, PhD

University of Washington

Dr. Matt Kaeberlein is a Professor of Pathology, Adjunct Professor of Genome Sciences, and Adjunct Professor of Oral Health Sciences at the University of Washington. Dr. Kaeberlein's research interests are focused on understanding the fundamental mechanisms linking normative aging and mitochondrial disease. He has published more than 150 papers in top scientific journals, and his work has been recognized by several prestigious awards, including a Breakthroughs in Gerontology Award from the Glenn Foundation, an Alzheimer's Association Young Investigator Award, an Ellison Medical Foundation New Scholar in Aging Award, an Undergraduate Research Mentor of the Year Award, and a Murdock Trust Award. In 2011, he was named the Vincent Cristofalo Rising Star in Aging Research by the American Federation for Aging Research. His contributions have also been recognized with Fellow status in the American Aging Association as well as the Gerontological Society of America. Dr. Kaeberlein is the current President of the American Aging Association and has served on their Executive Committee and Board of Directors since 2012. He is also a member of the Board of Directors for the Federation of American Societies for Experimental Biology. Dr. Kaeberlein currently serves on the editorial boards for Science, npj Aging and Mechanisms of Disease, Aging Cell, Cell Cycle, Oncotarget, BioEssays, PloS One, Frontiers in Genetics of Aging, F1000 Research, and Ageing Research Reviews.

Dr. Kaeberlein's scientific discoveries have generated significant public interest. He has been interviewed by most of the major local media outlets including the Seattle Times, KIRO radio and TV, KOMO radio and TV, and he has made studio appearances on KING 5 TV New Day Northwest and KIRO FM radio. Dr. Kaeberlein's research has been featured by numerous media outlets both nationally and internationally, including on the front page of the New York Times, and coverage in the UK Telegraph, the Boston Globe, the Chicago Tribune, Popular Science, Time Magazine, Scientific American, NPR, MIT Technology Review, Wired Magazine, Bloomberg News, USA Today, National Geographic, and many others.

In addition to his primary appointments, Dr. Kaeberlein served as a Distinguished Visiting Professor of Biochemistry at the Aging Research Institute of Guangdong Medical College in Dongguan, China from 2009–2014. He is currently the co-Director of the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging, the founding Director of the Healthy Aging and Longevity Research Institute at the University of Washington, and founder and co-Director of the Dog Aging Project.

Arlan Richardson, PhD

University of Oklahoma Health Sciences Center

Over the past 35 years, Dr. Richardson's research has focused on various aspects of aging, e.g., the anti-aging mechanism of dietary restriction and the role of reactive oxygen species in aging. His laboratory was the first group to show that dietary restriction altered the expression of genes through changes in specific transcription factors, and he is currently studying the effect of various levels of dietary restriction on the longevity of 8 genotypes of mice. Dr. Richardson's laboratory tested the oxidative stress theory of aging by measuring the effect of alterations in the antioxidant defense system on the lifespan and pathology of transgenic and knockout mice. While these animals show the expected alterations in sensitivity to oxidative stress and the accumulation of oxidative damage, only one, out of 18 mouse models showed any significant change in lifespan: Sod1 knockout mice. These data have led to the field re-evaluating the role oxidative damage plays in aging. Dr. Richardson has received several awards for his research in aging, e.g., the Nathan W. Shock Award, the Robert W. Kleemeier Award; the Denham Harman Research Award; the Irving Wright Award of Distinction in Aging; and the Lord Cohen Medal for Services to Gerontology.

Nicholas Stroustrup, PhD

Harvard University

Nicholas Stroustrup is an independent research fellow in the Department of Systems Biology at Harvard Medical School. In 2017, he will start as a group leader at the Center for Genomic Regulation in Barcelona, Spain. He designed and built a high-throughput imaging platform dubbed "the lifespan machine" that is now used by many research groups. His research focuses on the influence of genetic and environmental factors on stochastic processes in aging, using C. elegans as a model for how individuals vary in their response to interventions that alter health and lifespan.

Sponsors

Presented by

Digital Media and Reception will be supported by the Abbott Nutrition Health Institute

  • Abbott Nutrition Health Institute

Abstracts

Effect of Early Dietary Restriction on DNA Methylation
Arlan Richardson, PhD, Reynold Oklahoma Center on Aging at the University of Oklahoma Health Science Center, and Oklahoma City VA Medical Center

Dietary Restriction (DR) to date is the most consistent nutritional intervention to increase lifespan and retard aging in a wide variety of organisms; however, the molecular basis of DR's life-extending action is still unknown. Because early life DR has been shown to increase lifespan even when restriction is discontinued, we have explored whether DR retards aging through an epigenetic mechanism—DNA methylation. Alterations in DNA methylation at specific genes is critical during development and is a mechanism by which the transcriptional potential of cells can be altered for the life of an organism. Using RNAseq, we have identified a number of genes whose expression are potentially altered by DR through an epigenetic mechanism, i.e., genes whose expression is dramatically altered immediately after the implementation of DR and whose expression remains altered after returning the mice to an ad libitum diet. In our first screen of the data generated from the hypothalamus and colon, we identified 5 genes that showed large changes in expression after 1 month of DR and also continued to show these same changes when the mice were fed ad libitum for 2 months: Pomc, Hcrt, Foxg1 in the hypothalamus and Nts, Ncoa7 and Hsph1 in the colon. We are now using the latest and most rigorous techniques in next-generation-sequencing (Bisulphite Amplicon Sequencing and Methyl-Cap Sequencing) to determine if DR alters the DNA methylation status of CpG islands in specific promoter and intragenic regions in these genes in the genome of the hypothalamus and colon.
 
Coauthors: Willard M. Freeman, Dave R. Stanford, Benjamin C. Wronowski, and Archana Unnikrishnan, Reynold Oklahoma Center on Aging at the University of Oklahoma Health Science Center

Translational Geroscience: Teaching Old Dogs New Tricks
Matt Kaeberlein, PhD, Department of Pathology, University of Washington

A primary goal of geroscience is to improve health, longevity, and quality of life for people through basic and translational research into the biology of aging. While there has been significant progress in understanding the basic mechanisms of aging and developing interventions to delay aging in laboratory models, to date there has been limited application of these findings in a clinical setting. The goals of the Dog Aging Project are to move toward such translational application by (1) understanding the environmental and genetic determinants of healthy aging in companion (pet) dogs and (2) by directly intervening in the aging process to improve healthspan in dogs. The first goal is being pursued through a canine longitudinal study of aging in which we plan to enroll more than 10,000 companion dogs. The second goal is being pursued through a veterinary clinical trial to assess whether treatment with rapamycin can increase lifespan and improve healthspan in companion dogs, similar to what has been observed in laboratory mice. Here I will describe the initial data from the first phase of this rapamycin intervention trial, a short-term double-blind, placebo-controlled veterinary clinical trial involving 24 healthy, middle-aged companion dogs. We believe that results from this project will advance our understanding of the interaction between mTOR signaling and basic aging processes in dogs living in the human environment and could potentially extend the healthspan and lifespan of dogs, thus improving the quality of life for both dogs and their owners.

Longevity Mechanisms in Long-lived Mammals
Vera Gorbunova, PhD, University of Rochester

Animals have evolved a dramatic diversity of aging rates. Even within mammals, lifespans differ over 50-fold from four years in a mouse to 211 years in a bowhead whale. This natural diversity of lifespan can be exploited to understand the mechanisms of longevity. With modern technological advances now available, it became possible to undertake comparative study of aging at molecular level. Our goal is to identify mechanisms that allow such exceptionally long-lived animals to live long and healthy lives and then use these mechanisms to benefit human health. I will discuss our recent progress in the studies of long-lived mammalian species.
 
Coauthor: Andrei Seluanov, University of Rochester

Linking Molecular Interventions to Systemic Outcomes in Aging
Nicholas Stroustrup, PhD, Department of Systems Biology, Harvard Medical School

Aging involves a set of functional decline organs across many levels of biological organization. Organs, tissues, cells, and the molecular constituents of cells all change with age, and together determine an individual's health and the timing of his or her death. An emerging class of interventions in aging aims to directly target molecular mechanisms implicated in the aging process, with the idea that alterations in the underlying molecular biology should have knock-on, beneficial effects across a variety of age-associated symptoms. Several compounds found to extend good health and lifespan in the laboratory are now being evaluated clinically.
 
Conceptually, a major challenge to understanding how these interventions work is that, outside specific degenerative illnesses and mutant laboratory strains, no single molecular mechanism appears to be uniquely responsible for aging. Instead, a diverse set of mechanisms contribute simultaneously, with the integrated consequence of transforming a young individual into an old one. This multi-focal complexity suggests that successful interventions in aging should be rare, difficult, and weakly effective, the task of applying a thousand band-aids rather than one single miracle pill. How, then, do interventions targeting specific molecular mechanisms produce the beneficial, systemic effects in aging that we observe? My recent work in C. elegans highlights one way in which targeted molecular interventions could produce systemic effects, independent of any single molecular mechanism, depending instead on general principles of complex interdependent networks.
 
Coauthor: Walter Fontana, PhD, Harvard Medical School

Comparative Genomics of Lifespan Control
Vadim N. Gladyshev, PhD, Brigham and Women's Hospital, Harvard Medical School

Many human diseases are associated with aging, which is often their most significant risk factor. The aging process can be regulated during evolution, e.g. mammals show >100-fold difference in lifespan. We employ this diversity to shed light on mechanisms that regulate lifespan. For this, we apply comparative genomics to short- and long-lived species and carry out analyses across panels of mammals. We sequenced the genomes of several mammals with exceptional lifespan and identified genes that may contribute to their longevity. We also carried out analyses of gene expression, metabolites and elements across large panels of mammals. These studies point to both lineage-specific and common adaptations to longevity involving various pathways. One process relevant to lifespan control is the methionine pathway. Reduced methionine intake can extend lifespan in rodents by mimicking dietary restriction, but whether this regimen represents a general strategy for regulating aging has been controversial. We found that methionine restriction can extend lifespan of fruit flies and yeast, and this effect is dependent on the status of other amino acids. It is our hope that a better understanding of molecular mechanisms of mammalian lifespan control will lead to a better understanding of human diseases of aging.

Senescent Cell Elimination as a Means to Slow Aging and Disease
Jan M. van Deursen, PhD, Mayo Clinic

Cellular senescence has emerged as a potentially important contributor to aging and age-related disease and as an attractive target for therapeutic exploitation. Direct evidence for the deleterious effects of senescence in aging ortginates from BubRl-progeroid mice in which inactivation of the pleirnraa senescence pathGylr the elimination of pl6rhka'-positive senescent cells dramatically attenuates aging. Using transgenic mouse models that selectively kill p16rnk4u-positive cells, we have investigated the role of senescence in health and life span of normal mice, as well as its role in common age-related diseases. The implications of these studies for the design and effectiveness of senotherapies to extend healthy lifespan will be discussed.

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