Conference on
“Promoting the Health of an Aging Population”
at the Year 2004 Annual Meeting of the Gerontological Society of
America
Symposium Topic |
Chair/Co-Chair |
|
The Paradox of the Insulin Signaling Pathway and
Longevity |
Nir Barzilai |
|
Profiles of Healthy Aging: Quantifying Biological Age
and Function |
David Welsh |
|
Mitochondria and Aging: Cause or Effect? |
David Nicholls |
|
Pathobiology and Degenerative Disorders of Aging – A
Model Systems Approach |
Monica Driscoll |
|
Nature, Nurture, and Longevity: What Most of the World’s
Organisms Can Tell Us |
Stephen Helfand |
|
Whole Animal Energy Metabolism in Lab and Field: Is
There a Link to Aging? |
Roger McCarter |
|
The Cellular and Molecular Mechanisms of
Immunosenescence |
John Mountz |
|
Recent Breakthroughs in Understanding Progeria and
Premature Aging Syndromes |
Ted Brown |
|
Chance Events in Aging: Findings from Twin Studies |
Nicholas Greco/Michal Jazwinski |
(1) The Paradox of the Insulin Signaling Pathway
and Longevity
Chair: Nir Barzilai, Institute for Aging Research, Diabetes Center, Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx NY 10461
Down regulation of the insulin signaling pathway is associated
with significant longevity in lower species. However, similar alterations in insulin
signaling and insulin action are associated with variety of age-related
diseases leading to death in mammals. This symposium brings together experts in
insulin action to discuss this paradox. Dr. Rossetti will discuss the catabolic
and variable metabolic effects caused by activation of insulin signaling in the
brain, while opposite effects are noted by the activation of the peripheral
insulin signaling pathway. Because nematodes have only a central insulin
signaling pathway, this may explain part of the paradox. Dr. Barzilai, will
expand on the divergence between IGF and insulin signaling pathways in
mammalian and the role of low IGF states in longevity, further adding to the
explanation of the paradox. Dr. Barzilai will also demonstrate the harmful effects
of decreased insulin action on mammalian models. Finally, since intact insulin
action is required for mammalian longevity, Dr. Kenyon will summarize the
efforts to identify the relevant downstream pathways that may be common with
lower species. Such possibilities may include activation of small heat-shock proteins, upregulation of a wide variety
of genes, including cellular stress-response, antimicrobial and metabolic
genes, and downregulation of specific life-shortening genes with
potential impact on the elderly population.
L. Rossetti (Diabetes
Center, Albert Einstein College of Medicine, Bronx, NY) Insulin signaling pathway in
brain and in the periphery have opposite physiologic effects in mammalians
N. Barzilai (Institute
for Aging Research, Albert Einstein College of Medicine, Bronx, NY) Insulin
resistance as a risk for a shorter life span in mammalians
C. Kenyon (Department of Biochemistry and Biophysics, University of California, San Francisco, CA) How may longevity be induced by alterations in the insulin signaling pathway in nematodes
Open
slot: Late-breaking developments
(2) Profiles of Healthy Aging:
Quantifying Biological Age and Function
Chair: David Welsh, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA
While a person’s lifespan can be relatively easily measured, it
has become clear that chronological age is not equivalent to physiologic
age. Further, biomarkers that have been
shown to be predictive of future outcomes may not necessarily reflect current
functionality. Much work has been completed in recent years attempting to
define the concepts of physiologic (biologic) age, successful aging, and
frailty. Despite this effort there is no
universally accepted definition or “gold standard” of successful aging, nor is
there a definitive measurement instrument. This symposium will facilitate
discussion and thought on current and future methodologies by which to quantify
healthy or successful aging. Featured speakers will propose definitions of
successful (and unsuccessful) aging, review the data from investigations that
have validated indices or profiles of frailty and provide insights on future
directions to be pursued in validating quantitative measurement instruments
reflective of successful aging.
Kenneth Rockwood (Division of Geriatric Medicine, Dalhousie
University, Halifax, NS, Canada) The frailty index and biologic age
Linda P. Fried (The Johns Hopkins University School of Medicine, The
Johns Hopkins University School of Hygiene and Public Health, Baltimore,
MD) The phenotype of frailty
James F.
Fries* (Department of Medicine, Stanford University School of Medicine,
Palo Alto, CA) Measuring and monitoring success in compressing morbidity
Open slot: Late-breaking developments
(3) Mitochondria
and Aging: Cause or Effect?
Chair: David Nicholls, Buck Institute for Age Research, Novato CA
There is considerable evidence that
mitochondrial bioenergetic function is impaired in aging. A fundamental
question, however, is whether mitochondrial dysfunction is one of the causes of
aging, or whether mitochondrial dysfunction is merely a secondary
consequence of the aging process. David Nicholls will review current hypotheses
from the standpoint of a basic bioenergeticist, Christiaan Leeuwenburgh will
discuss current findings relating caloric restriction to mitochondrial function
and aging and Michael Breitenbach will cover insights into mitochondria and
aging obtained from yeast studies.
David Nicholls (Buck
Institute for Age Research, Novato CA) Mitochondria and aging: a review of current
hypotheses
Christiaan
Leeuwenburgh
(Biochemistry of Aging Laboratory, College of Health and Human Performance,
College of Medicine, Center for Exercise Science, University of Florida
Gainesville, FL) Aging, caloric restriction, and mitochondrial energy production
Michael
Breitenbach (Institute
of Genetics and General Biology, University of Salzburg, Salzburg, Austria) Yeast
aging and mitochondrial function
Open
slot: Late-breaking developments
(4) Pathobiology and Degenerative Disorders of
Aging – A Model Systems Approach
Chair: Monica Driscoll, Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ
One of the most promising themes to emerge from gerontological research in recent years is that several processes contributing to age-related decline involve molecular mechanisms conserved from lower organisms to humans. Moreover, modeling of specific disease states in experimental organisms has established powerful paradigms for age-associated degenerative diseases (such as Alzheimer's disease and Parkinson's disease) that are providing novel insights into disease progression and prevention. This symposium will highlight advances into our understanding of fundamental processes that contribute to age-related decline and underlie late-onset neurodegenerative conditions as gleaned from a model systems perspective.
Nancy M. Bonini (Department
of Biology and HHMI, University of Pennsylvania, Philadelphia, PA) Pathological
mechanisms for protein aggregation disorders in Drosophila
Frank LaFerla (Department
of Neurobiology and Behavior, University of California, Irvine, CA) Intracellular
Ab and synaptic dysfunction
modeled in mouse
Monica Driscoll (Department
of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ) The
genetic control of glycation, sarcopenia, and healthspan in C. elegans
(5) Nature, Nurture, and Longevity: What Most of the World’s
Organisms Can Tell Us
Chair: Stephen Helfand, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CN
One of the most interesting discoveries in recent years is the realization that many of the biochemical and physiological pathways involved in the determination of life span appear to be shared between organisms as diverse as mammals and yeast. Thus model organisms may be able to tell us more about the process of aging in humans than we could have imagined. One of the many advantages of model organisms is the ability to readily and rapidly manipulate their genetic constituency and epigenetic environment. This allows experimenters to quickly test physiological systems thought to be important in human longevity and to develop molecular and pharmaceutical interventions capable of extending life span. In this symposium we will examine the power of three important model systems: yeast, nematodes, and fruit flies to help us understand the basic biology of the aging process and identify interventions, both pharmaceutical and environmental, that may contribute to our understanding of human aging and the potential amelioration of age-associated diseases.
David Sinclair (Department
of Pathology, Harvard Medical School, Boston, MA) Small molecule and genetic
mimetics of calorie restriction
Gordon Lithgow (Buck
Institute for Age Research, Novato CA) Lifespan determination by stress response in
C. elegans
Stephen L. Helfand (Department of Genetics and Developmental Biology,
University of Connecticut Health Center, Farmington, CN) I'm not dead yet: a gene
that doubles the life span of the fly
(6) Whole Animal
Energy Metabolism in Lab and Field: Is There a Link to Aging?
Chair: Roger McCarter, Department of Physiology, University of Texas Health Science Center at San Antonio and GRECC, Audie L. Murphy Memorial VA Hospital, San Antonio, TX
There is
widespread belief that energy metabolism, in particular oxidative energy
metabolism involves deleterious consequences which accumulate over the lifespan
and constitute important mechanisms of aging.
This view is consistent with theories of aging, from Rate of Living to
Oxidative Free Radical and Mitochondrial theories of aging. It is also consistent with the age-retarding
effects of calorie restriction, in which it is known that the anti-aging effect
is a consequence of reduced daily energy intake, rather than specific nutrient
intake. Mechanisms linking energy
metabolism to aging processes are however controversial and have not been
precisely identified. The goal of this
symposium is to critically evaluate the involvement of whole animal energy
metabolism in aging across wide phylogenetic lines. Dr. Van Voorhies will discuss possible links
between metabolic rate and aging in invertebrates, with particular emphasis on
provocative new findings in different lines of Drosophila melanogaster. Dr. Kemnitz will evaluate the relevance of
total versus resting energy expenditure in mechanistic effects of lifelong
calorie restriction in non-human primates.
Dr. McCarter will examine evidence in calorie restricted laboratory rats
and mice of a link between longevity and altered energy metabolism, for both
sedentary and vigorously exercising animals.
Dr. Speakman will discuss
measurement of total daily energy expenditure of animals in the field and
evaluate the possible relevance of metabolic rate to aging in non-laboratory
settings. These presentations will
provide a comprehensive overview of evidence, at the level of the whole animal,
of the potential importance of energy metabolism in mechanisms of aging.
Wayne Van Voorhies
(Department of Molecular Biology, New Mexico State University, Los Cruces, NM) Metabolic
rate and lifespan in Drosophila
Roger
McCarter (Department of
Physiology, University of Texas Health Science Center, San Antonio, TX) Metabolic
rate over the lifespan of calorie restricted laboratory rats and mice
Joseph
Kemnitz (Primate Center,
University of Wisconsin, Madison, WI) Energy metabolism and nutrition in aging
non- human primates
John Speakman (Department
of Zoology, University of Aberdeen, Aberdeen, Great Britain) Energy
metabolism of animals in the field
(7) The Cellular
and Molecular Mechanisms of Immunosenescence
Chair: John Mountz, University of Alabama at Birmingham, Department of Medicine, Division of Clinical Immunology and Rheumatology, Birmingham, AL
The hallmark of immune senescence in the peripheral lymphoid
system is an age-related defect in the CD4+ T cell helper response
as well as CD8+ cytotoxic T cell response. The process of immune senescence parallels
the biological process of aging as one of the primary models for cell
senescence. With aging this replicative senescence is associated with telomere
shortening and slowing and arrest of the cell cycle. Dr. Effros will discuss human immune
senescence with a focus on the CD8 cytotoxic T cell population. The thymic output of CD8+ T cells
decreases faster than CD4+ T cells, and peripheral expansion of CD8+
T cells is decreased and becomes oligoclonal with age. Underlying this dramatic alteration in human
CD8+ T cell population dynamics is a cell cycle arrest resulting in
replicative senescence. Furthermore, T
cells that have undergone replicative senescence exhibit down modulation of
CD28. The key role of cytotoxic T cells
in elderly humans is to combat viral infection.
To this end, most vaccines that are used in the elderly are designed to
enhance the CD8 cytotoxic T cell response.
Dr. Donna Murasko will discuss the limitations and efficacy of influenza
vaccine in the elderly. This vaccine
relies heavily on the production of Th1 T cells and CD8+ cytotoxic T
cell response. Finally, the CD4+
T cell response is critical to promote both B cell response and CD8 cytotoxic T
cell response. Dr. Goronzy will discuss
mechanisms of decreased CD4+ T cell response in the elderly. The efficiency of CD4+ T cell
response is highly dependent on the CD28 signaling pathway. Dr. Goronzy will discuss the molecular basis
of modulators of CD28 gene transcription as a fundamental mechanism for the
decrease in the T cell response with age.
Dr. Mountz will discuss his work indicating the critical role of both a
robust proliferative response and an active apoptotic process in T cells, which
is associated with longevity.
Rita Effros (Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA) T cell replicative senescence in CD28 expression
Donna Murasko (College
of Arts and Sciences, Drexel University, Philadelphia, PA) Age-related decrease in cytotoxic
T cells to influenza
Jorg Goronzy (Department of Medicine and Immunology, Mayo Clinic, Rochester, MN) CD4+ T cells signaling defects with aging, role of CD28 signaling
John Mountz (Center
for Aging, University of Alabama at Birmingham, Birmingham, AL) Genetic
analysis of T cell senescence in mice and man
(8) Recent
Breakthroughs in Understanding Progeria and Premature Aging Syndromes
Chair: W. Ted Brown, Department of Human Genetics, Institute for Basic Research in Developmental Disabilities, Staten Island, NY
Progeria, the Hutchinson-Gilford progeria
syndrome (HGPS) (from the Greek for premature aging), is a rare disease of
childhood with striking features resembling premature aging. Other
"premature aging syndromes", such as Werner syndrome (progeria of the
adult) and Down syndrome, have provided valuable information regarding the
phenomenon of aging. Important clues about aging may also result from
understanding the pathogenic mechanisms involved in HGPS. Recently, it was
discovered that de novo mutations in the gene LMNA encoding the lamin A/C
proteins cause HGPS. Mutations of lamin A have been found in six other
laminopathic disorders (Emery-Dreyfuss muscular dystrophy, dilated
cardiomyopathy, familial partial lipodystrophy, limb girdle muscular dystrophy,
Charcot-Marie-Tooth II, and mandibuloacral dysplasia). LMNA mutations
also are found in several adult Werner syndrome progeric patients with atypical
features that are negative for WRN mutations. This symposium will present
an overview of HGPS and the latest research on the disorder, as well as cover
funding opportunities.
W. Ted Brown (Department of
Human Genetics, Institute for Basic Research in Developmental Disabilities,
Staten Island, NY) Overview of HGPS and comparison with other laminopathies and premature
aging syndromes
Francis Collins (National
Institute for Human Genome Research, Bethesda, MD) Lamin defects in Progeria -The
HGPS gene defect and what it means
Leslie Gordon (Progeria
Research Foundation, Peabody, MA) Prospects for therapy of HGPS and the role
of the Progeria Research Foundation in supporting research
Open slot: Late-breaking developments
(9) Chance Events in Aging: Findings from Twin
Studies
Co-Chairs: Nicholas Greco1 and S. Michal Jazwinski2, 1Department of Anatomy and Neurobiology, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA, 2Louisiana State University Health Sciences Center, New Orleans, LA
Many events that occur during aging have been tied to genetic make-up. Twin research provides us with a unique opportunity to investigate events of aging that are both the result of genetics and chance events or non-genetic changes. Non-genetic cellular variations as a result of development have been found to influence the outcomes of the physiological aging process. Many chance events of aging occur as a result of environmental influence. Through longitudinal twin studies, it has been found that both genetic and environmental influences have an impact on normative cognitive change and age of onset.
Caleb Finch (Department of Neurobiology and School of Gerontology, University of Southern California, Los Angeles, CA) Cellular variations during development influence outcomes of aging
Margaret Gatz (Department of Psychology and School
of Gerontology, University of Southern California, Los Angeles, CA), Chandra
Reynolds (University of California Riverside, Riverside, CA), Nancy
Pederson (Department of Psychology, Virginia Commonwealth Unversity,
Richmond, VA) Genetic and environmental influences on normative cognitive change
Gerald McClearn* (Center for Developmental and Health Genetics, Pennsylvania State University, State College, PA) Genetics of complex behaviors in aging