AFAR Research Grant Program

height=

Edward Bartlett, PhD
Assistant Professor
Purdue University

A comparison of auditory temporal processing assessed non-invasively in aged vs. young rats


Many hearing deficits in older people cannot be attributed simply to age-related hearing loss because they endure even when hearing loss is compensated. In particular, reduced abilities to perceive rapid changes in sound amplitude or frequency are thought to result in reduced speech perception and comprehension. The underlying neural causes of these perceptual problems are poorly understood, but neural activities can be measured during sounds. Dr. Bartlett will study non-invasively neural population responses from the auditory brainstem and midbrain of aged animals and compare the responses to those in younger animals. The results from this study will identify simple and complex sound stimulus features that are represented differently by neurons between young and aged animals. The long-term goal of this project is to provide clear targets for pharmacologic or behavioral therapy to treat the age-related hearing deficits.

height=

Nancy Dennis, PhD
Assistant Professor of Psychology
Pennsylvania State University

Age-related changes in neural recruitment associated with cognitive conrol of memory processes


Age-related declines in memory are typical of normal healthy aging. However, declines that exceed a certain threshold are often the first signs/symptoms of diseases and disorders such as Mild Cognitive Impairment, Alzheimer's disease and dementia. Behavioral research shows that while aging is associated with increased incidental forgetting (accidental forgetting of items you intended to remember), it is also associated with impairments in intentional forgetting (strategic process of overtly trying to forget). Dr. Dennis's proposal will examine the neural mechanisms underlying intentional forgetting processes in both young and older adults and examine how they differ from those mediating incidental forgetting. Understanding the neural basis that mediates memory differences across the lifespan is critical for understanding the difference between normal development changes and more severe disease-associated changes.

height=

James Edwards, DPhil
Lecturer in Musculoskeletal Ageing
University of Oxford - Institute of Musculoskeletal Sciences

Regulation of Bone Mass by Aging-Related Genes


Age-related bone loss represents an enduring challenge to health care systems worldwide. Over 44 million Americans currently suffer from this condition, resulting in over 2 million fractures each year, costing an estimated $19 billion annually. This devastating skeletal deterioration is a direct result of impairments in the physiological regulatory responses of both major cell types in bone. Dr. Edwards will investigate the common mechanisms known to regulate the aging process and those controlling normal bone mass. Specifically he will analyze novel regulators of cell replication and formation using standard and state-of-the-art techniques to identify novel therapeutic approaches in the treatment of age-related bone loss, such as osteoporosis.

height=

Troy Ghashghaei, PhD
Assistant Professor
North Carolina State University

Aging of the adult neural stem cell niche


The adult central nervous system (CNS) lacks internal mechanisms for replacing its damaged, diseased, or aged tissue. Many central nervous system disorders associated with aging may be caused by elevated levels of oxidative stress resulting from exposure to toxins, pollutants, and carcinogens during aging. Discovery of an endogenous adult neural stem cell niche (SCN), however, has raised hope for an alternative approach to utilize mechanisms for cell replacement in the CNS. Dr. Ghashghaei's research will focus on determining whether or not responsiveness to oxidative stress is associated with remodeling and repair of the SCN in the aged brain. Mechanisms unraveled by his studies may open up new ways of looking at the causes of a number of aging-related CNS disorders and provide alternative therapeutic approaches in the future treatment of these diseases.

height=

Andreana Haley, PhD
Assistant Professor
The University of Texas at Austin

A Pilot Study of the Effects of Aerobic Exercise on Neuronal Integrity in Middle-aged and Older Adults with Hypertension


High blood pressure in midlife is the most common treatable risk factor for late-life cognitive impairment. Since cognition is an important determinant of health status, quality of life, and functional ability, interventions that ensure healthy cognitive aging will be invaluable in reducing future health care costs and caregiver burden. Dr. Haley's project will examine the efficacy of a moderate-intensity exercise intervention to improve brain health and cognitive function in middle-aged and older adults with high blood pressure. This research may lead to the development and optimization of early interventions that preserve and enhance cognitive function in order to ensure the successful aging of our growing population of older adults.

height=

Malene Hansen, PhD
Assistant Professor
Burnham Institute for Medical Research

Identification of autophagy reglators important for the response to dietary restriction in C. elegans


Autophagy is a cellular recycling process by which the cell degrades its own components. This process is up-regulated in response to dietary restriction, which extends lifespan in multiple organisms as a consequence of a reduced food intake without malnutrition. Dr. Hansen's research will address how healthy aging can be achieved by identifying molecular mechanisms influencing aging in response to dietary restriction. Specifically, her team will seek to identify genes that function to increase autophagy in long-lived animals subjected to dietary restriction. Identification of new genes with functions in autophagy and dietary restriction will provide important new insights not only into organismal aging but might also help developing treatment for such age-related diseases.

height=

Sangwon Kim, PhD
Assistant Professor
University of Pennsylvania

The role of phosphoinositides in cellular growth and aging


Calorie restriction (CR), or limiting the amount of food to 60-70% of normal food intake, extends the lifespan of virtually all laboratory organisms; yet mechanistic understanding of how CR prolongs life and wards off diseases of aging is poorly understood. A growing body of evidence indicates a strong link between ageing and cell's ability to remove cellular wastes, called autophagy, and caloric restriction is the most physiological inducer of authopagy. Dr. Sangwon aims to address this issue by examining the mTOR (mammalian target of rapamycin) pathway, which plays a key role in nutrient sensing and cell proliferation. Results of his study may provide the groundwork for the design of new drugs or therapies to improve symptoms of age-related disorders such as diabetes or cancer.

height=

Agnes Lacreuse, PhD
Assistant Professor
University of Massachusetts

Effects of testosterone on cognition, emotion and motor function in aged male macaques


Human studies on the effects of testosterone replacement on cognitive aging have provided inconsistent results and it is still debated whether testosterone replacement is a desirable intervention for older men. Dr. Lacreuse seeks to clarify this issue by studying a primate model of human aging. She will examine whether testosterone replacement in aged male macaques benefits cognitive function, motor ability, and emotional reactivity and whether specific genes influence these behavioral outcomes. The findings will constitute the first data on the effects of testosterone on age-related cognitive decline in a primate model of human aging. They will form the basis for further studies aimed at understanding the conditions under which testosterone may provide cognitive benefits in older males.

height=

Brian Lee, PhD
Assistant Professor, Epidemiology and Biostatistics
Drexel University School of Public Health

Effects of midlife blood pressure, anti-hypertensive medication use, and genetic risk factors on white matter health in aging


Although prior research studies suggest a correlation between high blood pressure in midlife and worse cognitive function and dementia, inconsistent data challenges whether the use of anti-hypertensive medication is beneficial. Dr. Lee hopes to address these gaps in knowledge by using neuroimaging data to examine midlife blood pressure relative to brain health in aging. He seeks to determine whether 1) anti-hypertensive medication reduces brain deterioration and 2) specific genetic factors modify the effects of blood pressure and anti-hypertensive medication on brain health. Findings from the proposed research may help in developing new approaches for prevention and/or mitigation of brain health deterioration during aging.

height=

David Lombard, MD, PhD
Assistant Professor
University of Michigan

SIR-2.4 regulation of DAF-16 function in C. elegans


Two protein families, the FoxO transcription factors and sirtuin, regulate lifespan as well as a variety of critical processes such as stress resistance, metabolism and tumor suppression in different organisms. While sirtuin proteins are implicated in promoting increased longevity in invertebrates, the FoxO function is implicated in a variety of age-associated diseases in mammals, particularly ovarian failure, inflammatory disease, and cancer. In collaboration with Dr. Ao-Lin Hsu's laboratory, also at the University of Michigan, Dr. Lombard has already found that the protein SIR-2.4 plays a vital role in promoting the activity of DAF-16, the single FoxO protein in C. elegans. DAF-16 is known to be central to stress resistance and lifespan in C. elegans. He now seeks to illuminate the connection between SIR-2.4 and DAF-16. His work may provide insights into novel functions for sirtuin proteins in the context of FoxO regulation, and potentially in suppression of age-associated disease.

height=

Jamie Maguire, PhD
Assistant Professor
Tufts University School of Medicine

GABAergic control of the HPA axis in the pathophysiology of anxiety and depression in aging


Abnormal activation of the stress response and elevated levels of stress hormones has been associated with major depression in younger people. As stress hormone levels increase with age, they may play a role in depression or anxiety specifically in the aged population. Dr. Maguire's project will investigate the impact of the body's stress response on anxiety and depression associated with aging. In doing so, Dr. Maguire seeks to test the hypothesis that deficiencies in the regulation of the stress response may induce mood disorders associated with aging. The study will provide insight into the mechanism of stress regulation in aging and can potentially benefit a large percentage of individuals struggling with mood disorders associated with aging.

height=

Shane Rea, PhD
Assistant Professor
University of Texas Health Science Center at San Antonio

Nuclear Checkpoint Signaling Connects Ribosomal Translation with Longevity Specification in the C. elegans Mitochondrial Mutants


Inside everybody's cells there are tiny factories called mitochondria that make energy and perform a variety of other essential tasks. Mitochondria make their energy using molecular-sized machines that run on the flow of electrical charge; defects in this energy production are linked to age-associated diseases such as Parkinson's and Alzheimer's disease. However, more recent studies have discovered that disruptions in mitochondrial energy production have resulted in life extension in other species. Dr. Rea's study aims to fill a knowledge void on how this dysfunction results in an increased lifespan in a variety of species and results may help direct research toward tailor-made strategies for optimizing human health into old age.

height=

Cynthia Reinhart-King, PhD
Assistant Professor
Cornell University

Age-related blood vessel stiffening and atheroslerosis progression


Atherosclerosis is an inflammatory disease marked by the formation of plaques in blood vessel walls, restricting blood flow and potentially leading to heart failure or aneurysm. Affecting over 50% of the population over 65, atherosclerosis and aging are considered to be linked though the mechanism is unclear. Dr. Reinhart-King's project is specifically focused on understanding how aging-related changes in blood vessel structure and composition contribute to atherosclerosis, with the long term goal of developing strategies and therapeutic targets to prevent atherosclerosis progression.

height=

Bradley Sutton, PhD
Assistant Professor of Bioengineering
University of Illinois

Age-related demyelination in motor pathways predicts reductions in fine motor control


Muscle control in the hands and fingers declines with age and can have a critical impact on activities of daily living and recreational pursuits. This age-related decline in manual muscle control, however, appears to be in contrast with evidence for relatively preserved muscle control in oral muscles, such as the lips and tongue. Dr. Sutton's project will examine whether characteristics of the nerve fibers that connect the brain with the muscles can predict these selective declines in fine muscle control with age. This will provide a way to quantify the current state of decline. Additionally, it will provide a means of assessment for therapeutic interventions, such as training and pharmaceutical studies, that may seek to reverse these declines in the future.

AFAR Affiliate Research Grant Program

height=

Lina Shehadeh, PhD
Research Assistant Professor
University of Miami Miller School of Medicine

Role of miR-30e in the Collagen-Osteogenic Transition in Senescent Vascular Smooth Muscle Cells


Aging is an independent risk factor for vascular diseases such as atherosclerosis and restenosis as blood vessels become calcified, or hardened, with age. Dr. Shehadeh's research has found that a particular microRNA, small RNA molecule that regulates genes and entire biological pathways, runs anti-calcification and anti-aging programs. Dr. Shehadeh will investigate this particular microRNA called miR-30e, and its ability to regulate calcification properties in vascular smooth muscle and mesenchymal stem cells in young and old mice. Since aging predisposes many diseases, Dr. Shehadeh's evaluation of this micoRNA's molecular function may have positive therapeutic implications not only for age-associated vascular calcification, but also for age-related diseases and disorders in general.

height=

Noel Marysa Ziebarth, PhD
Assistant Professor
University of Miami

Atomic Force Microscopy to Elucidate Age-Related Changes in Structure and Mechanics of the Ocular Lens


Both presbyopia, the loss of the ability to view objects at various distances, and cataract, the loss of lens transparency and a leading cause of visual loss and blindness, are inevitable conditions resulting from natural aging processes affecting all people over the age of 50. Dr. Ziebarth's research will investigate age-related changes in lens mechanics and structure in order to understand their role in the loss of near vision and the development of cataract with age. She will be using state-of-the-art Atomic Force Microscopy techniques and it is anticipated that her study will provide vital information about the mechanisms of these conditions to assist researchers in developing techniques for the restoration of normal vision and the prevention of cataract.

Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease

height=

Christopher Ackerson, PhD
Assistant Professor
Colorado State University

Probing and Disrupting Actin/Cofilin Rods


Deterioration of brain function is a hallmark of the aging process. At the molecular level, proteins called actin and cofilin can malfunction and assemble into pathological structures called that look like big rods. These actin/cofilin rods are present in a wide variety of brain function impairments such as Alzheimer's disease, Huntington's disease, and Down's Syndrome. Dr. Ackerson will investigate whether precisely formulated nanoparticles can prevent or disrupt protein/protein interactions, particularly the actin/cofiliin interaction. The tools Dr. Ackerson employs to achieve the prevention or disruption of these interactions may someday become the foundation of drugs which prevent or reverse the molecular aspects of disorders of brain function in age-related diseases.

height=

Fenghua Hu, PhD
Research Scientist
Cornell University

Progranulin function and signaling in microglia cells


Increased levels of the progranulin protein are found in microglia cells in many neurodegenerative diseases, including Alzheimer's disease. Furthermore, genetic mutations of progranulin are linked to frontotemporal lobar degeneration, a common neurodegenerative disease. Microglia cells are the mediators of inflammatory responses in the brain, which play an important role in neurodegeneration. Dr. Hu aims to determine potential functions of progranulin and mechanisms of progranulin action in the microglia cells, which ultimately have implications for many neurodegenerative diseases.

height=

Vinay Parikh, PhD
Assistant Professor
Temple University

Interactions between TrkA signaling and APP processing in Aging: impact on forebrain cholinergic circuits and cognition


Neurotransmitters serve as chemical signaling molecules in the brain. When the release of acetylcholine, a specific neurotransmitter in the forebrain that is critical for supporting attentional functions, is disrupted, it generates impairments that represent core symptoms of age-related dementias and Alzheimer's disease. Dr. Parikh's research will investigate the neurochemical mechanisms that contribute to age-related vulnerability of forebraincholinergic neurons and associated cognitive decline. The findings generated from this study may be used to not only explore molecular mechanisms underlying age-related cognitive impairments but also develop a treatment for cognitive dysfunction.

height=

Nikki Stricker, PhD
Neuropsychologist
Boston VA Healthcare System

Does retrogenesis explain regional white matter integrity in MCI?


Neuropathologists have observed that the pattern of degenerative brain changes in Alzheimer's disease appears to occur in the reverse order as that of normal brain development, particularly in white matter. Dr. Stricker's study will investigate this pattern of white matter changes at early stages of Alzheimer's disease and aim to help define early patterns of neurodegeneration. By understanding the pattern of neurodegenerative changes, specific brain regions along this pathway can be better targeted for early detection and clinical trials. Determining the role of white matter changes in the development of Alzheimer's disease may aid in earlier detection and alter future treatment efforts.

height=

Qi Zhang, PhD
Assistant Professor
VUMC, Vanderbilt University

A mechanistic study of presynaptic dysfunction in Alzheimer's disease


Alzheimer's disease is one of the most prevalent neurodegenerative diseases among older Americans. The cognitive deficits associated with Alzheimer's disease are parallel to the degradation of synapses, connections between billions of neurons that construct the human brain. Tightly controlled, synapses are the physical basis of learning and memory that permit neurons to pass electrical or chemical signals to other cells. The role of Amyloid-beta (the peptide that is the main constituent in amyloid plaques in the AD brain) in disrupting synaptic transmission is still unclear, and this project tries to better understand how Amyloid-beta regulates presynaptic function. Dr. Zhang has devised an imaging method (Qdot-enabled single vesicle tracking) that allows his group to systematically examine the turnover of synaptic vesicles and their membranes and proteins. Although this research is currently in its infancy, it has the potential to make substantial advances on the molecular and cellular pathogenesis of Alzheimer's and thus brings us one step closer to the cure of this devastating disease.

Julie Martin Mid-Career Awards in Aging Research

Kenneth Poss, PhD
Associate Professor
Duke University Medical Center

Cardiac Aging and Regeneration in Zebrafish


The injured mammalian heart shows little or no regeneration of new muscle, a deficiency that contributes to the impact heart disease has in this country. By contrast, the zebrafish, a laboratory model system, robustly generates muscle after injury. Dr. Poss’s project involves developing new experimental tools to examine cardiac regeneration in adult zebrafish. Ascertaining how regenerative ability changes with age will provide the unique opportunity to understand molecular influences on cardiac aging and regeneration. His long-term goal is to apply these influences toward therapies that enhance myocardial regeneration and reduce age-related cardiac disease in humans.

Joanne Turner, PhD
Associate Professor
The Ohio State University

Divergent macrophage-pathogen interactions in old age


The elderly account for one fifth of all tuberculosis cases in the U.S. and Europe. Mycobacterium tuberculosis is the causative agent of tuberculosis, a pulmonary pathogen that interacts with host cells. In this initial interaction, M. tuberculosis develops evasive mechanisms to counter its demise. Analysis of these interactions in old mice indicate that host cells change as we age, significantly changing their response to infectious agents. Dr. Turner aims to define the different mechanisms by which host cells interact with M. tuberculosis and determine their impact on the control of infection. While this has immediate application to tuberculosis control, studies are likely to have broader application to more effective vaccine design for other infectious diseases for the elderly.

Glenn/AFAR Breakthroughs in Gerontology (BIG) Award

Daniel Promislow, DPhil
Professor
University of Georgia

Causes and consequences of aging in metabolomic networks


Researchers have identified scores of genes that extend lifespan in lab animals, but it is unknown whether these same genes can account for natural variation in rates of aging, or explain why some traits within individuals biologically age at a faster rate than others. Dr. Promislow’s work aims to identify genes that explain variation in rates of aging not only among lineages within a population but traits within individuals. He will use a systems biology approach, identifying networks of small molecules (metabolites) in a fruit fly model. This work aims to identify factors that affect rates of change in network structure, as well as determine whether dietary restriction can slow the rate of decline in network integrity. Analysis of molecular networks has been used to seek out causal genes, identify drug targets, and develop more accurate prognoses in diseases such as cancer and heart failure. Dr. Promislow aims to bring these same tools to the study of aging and age-related diseases, with the hope of developing more accurate diagnosis and treatment.

Peter Rabinovitch, MD, PhD
Professor
University of Washington

Next generation discovery of mTOR effects on mRNA translation and the proteome in aging


The mammalian target of rapamycin (mTOR) is a protein that regulates processes such as cell growth and survival. In some human diseases, especially certain cancers, the mTOR pathway is impaired. Recent NIA studies have shown treatment of mice with rapamycin, a bacterial product that inhibits mTOR, results in lifepan extension. Dr. Rabinovitch’s research hopes to address what specific effects of rapamycin are associated with lifespan or healthspan benefits. If the mechanism of rapamycin-associated health benefits can be understood at the protein level, then it is possible in the future that these benefits could be delivered more specifically and without side effects by a more targeted approach. The knowledge gained from Dr. Rabinovitch’s work has the promise to have positive impacts in a broad spectrum of age-related diseases and disorders.

Ellison Medical Foundation/AFAR Postdoctoral Fellows

Marcelo Caetano, PhD
Postdoctoral research associate
John B. Pierce Laboratory
Effect of aging on temporal processing by the prefrontal cortex


The ability to retain temporarily-relevant information for a short period of time, referred to as working memory, is reduced as we age. One hypothesis of why this ability is reduced as we age is that our neurons gradually lose their ability to communicate with each other, at which point the information you’re trying to keep in mind just “fades away.” Dr. Caetano’s main focus will be to understand the neural basis for this phenomenon. Specifically, his research will aim on describing the differences in neural activity between a younger and an older brain when these brains are engaged in remembering information over different lengths of time. Understanding the basic mechanisms that underlie memory deficits is key to the development of methods to delay, stop, or even reverse those aging effects.

Della David, PhD
Postdoctoral Fellow
University of California, San Francisco
Understanding the molecular basis of age-related disruption of protein homeostasis


In diseases such as Alzheimer’s, Parkinson’s and Huntington’s, very specific proteins form aggregates or clumps of solid material. Inherent protein aggregation prevents proteins from normal functioning and could be toxic to the organism. Aging is a major factor for this inherent protein aggregation. Using the roundworm C.elegans, Dr. David will investigate the mechanisms behind non-disease associated protein aggregation. She will seek to identify a factor or factors that prevent age-dependent inherent protein aggregation which may eventually ameliorate a wide variety of neurodegenerative diseases.

Fabio Demontis, PhD
Harvard Medical School

Regulation of muscle aging by FOXO transcriptional activity in Drosophila melanogaster


Tissues have distinct rates of aging and different sensitivity to pro-aging stimuli. In particular, muscles undergo dramatic age-related deterioration while other tissues are remarkably preserved. Although decreased muscle strength is one of most remarkable features of human aging, the underlying molecular mechanisms are largely unknown. FOXO/DAF-16, a transcription factor (a protein that controls when genes are switched on or off), was recently discovered to delay the gradual decay of muscle function observed during aging. Dr. Demontis aims to understand why muscle ages precociously in comparison with other tissues and how FOXO and associated regulators can preserve muscle strength during aging. Altogether, his study will provide a better understanding of muscle aging and will possibly provide a basis for therapeutic interventions to extend the healthy lifespan in humans.

Hinco Gierman, PhD
Stanford University School of Medicine

Testing the Damage Accumulation Theory of Aging: Can Aging be Reversed?


The process of aging is poorly understood. One hypothesis is based on the concept that damage, due to either normal toxic by-products of metabolism or inefficient repair/defensive systems, accumulates throughout the entire lifespan and causes aging. However, a recent finding by the lab of Stuart Kim suggests that deregulation (drift) of developmental genes causes aging. Dr. Gierman proposes an experiment in the roundworm C. elegans, that will test whether aging can be reversed (as predicted by the developmental drift theory) or merely slowed down (as predicted by the damage accumulation theory). The research will be extended to humans by performing whole genome sequencing on supercentenarians; people of 110 years or older. Dr. Gierman will investigate whether supercentenarians possess gene variants that are implicated in the prevention of damage accumulation or developmental drift. Dr. Gierman’s research will not only address a fundamental question of biology but also increase understanding of the cause of age-related diseases in biology and medicine.

Yuko Hara, PhD
Postdoctoral Fellow
Mount Sinai School of Medicine

Relationships between dentate gyrus synaptic subtypes and age-related memory impairment in rhesus monkesy


Age-related memory impairment occurs in many mammalian species, including humans. Many women undergoing the menopausal transition also report problems with memory. Dr. Hara will examine the dentate gyrus (DG), a brain area particularly vulnerable to the effects of aging, and its synapses (junctions between nerve cells that transmit and receive nerve impulses,). She will study rhesus monkeys because they develop age-related deficits in DG-dependent memory and undergo menopause similar to humans. The overall goal of her project is to determine the subtypes of DG synapses that are selectively vulnerable to aging. Findings will have major implications for normal age-related memory impairment as well as for menopause-associated cognitive symptoms in humans. In addition, the results may further lead to potential behavioral therapies and/or pharmacological agents that help protect the subtypes of DG synapses that are vulnerable to aging.

Hadise Kabil, PhD
Postdoctoral Fellow
University of Michigan

Modulation of lifespan by the transsulfuration pathway


The lifespan of organisms ranging from yeast to mammals can be extended by decreasing the amount of food intake, which is also known as dietary restriction (DR). However, how reduced food intake improves health and translates into longer lifespan is not clearly understood. Through her research, Dr. Kabil has identified a metabolic pathway called transsulfuration as a novel player in DR-mediated lifespan extension and aging in flies. Dr. Kabil aims to understand how the DR regimen works to extend lifespan and improve health. Results may provide candidate therapeutic targets for human lifespan extension and for treatment of a range of age-associated diseases including cancer, Alzheimer’s disease and diabetes.

Luv Kashyap, PhD
Postdoctoral Scholar
University of Pittsburgh

Investigating the correlation between reduction in mevalonate kinase levels and onset of sarcopenia using the nematode Caenorhabditis elegans


One of the most common issues associated with increasing age is the decline in muscle strength and mass (sarcopenia) which causes weakness and problems in mobility. Specifically, Dr. Kashyap will aim to identify the molecular mechanisms and genes involved in the onset of sarcopenia in humans by studying it in C. elegans. Dr. Kashyap’s research will investigate why a mevalonate kinase gene mvk-1, is needed for successful muscle aging. This gene helps make cholesterol in humans. Dr. Kashyap will seek to understand whether use of statin drugs could have harmful effects on muscle aging. His results may lead to a better understanding of the cause(s) of sarcopenia and new treatments for people affected which will hopefully let the older people live more active and independent lives.

Sathish Kasina, PhD
Postdoctoral Fellow
University of Michigan School of Medicine

CXCL12/CXCR4 axis Promotion of BPH in the Aging Prostate


Benign prostatic hyperplasia (BPH) is one of the most common benign proliferative conditions associated with aging in men. BPH is a non-malignant condition of the prostate which, conservatively, affects 25-35% of men aged 60 or older and results in a tremendous negative impact on quality of life. The negative impact is due to various co-morbidities that develop concurrent with BPH, collectively termed lower urinary tract symptoms, or LUTS. Dr. Kasina’s research will specifically investigate the role of CXCL12 (a CXC-type chemokine) in the aging prostate, which may ultimately lead to the development of therapeutics aimed at delaying or abrogating the development of BPH/LUTS or to effectively reverse the development of BPH/LUTS among aging men.

William Mair, PhD
Research Associate
The Salk Institute for Biological Studies

Characterizing CRTC-1, a novel AMPK and Calcineurin Target for Lifespan Extension in C. elegans


In animals ranging from single celled yeast to non-human primates, reducing food intake robustly extends lifespan. Such ‘dietary restriction’ not only increases longevity but also makes animals resistant to many age-related pathologies including neurodegenerative diseases and cancer. To exert its effects on disease and aging, varying energy intake must trigger programmed changes within the organisms’ genes. Recently, Dr. Mair identified a transcriptional cofactor (CRTC-1) in the nematode worm C. elegans, and determined that when nutrients are low it is repressed by gain of function of AMP-kinase, or loss of function of the phosphatase Calcineurin, both of which extend longevity in C. elegans. This AFAR grant is aimed at characterizing the genes/ proteins that CRTC-1 regulates in order regulate lifespan under different nutritional conditions. Dr. Mair’s work may ultimately translate into protection against age-onset disorders like diabetes and cancer in mammals.

Haakon Nygaard, MD
Post-doctoral fellow
Yale University School of Medicine

The role of cellular prion protein in beta-amyloid-induced epilepsy and early death in Alzheimer's disease mouse model


Patients with Alzheimer’s disease experience a spectrum of cognitive impairments, particularly related to memory retrieval and storage. However, Alzheimer’s disease also affects other brain functions, some of which can be very disabling. One of these symptoms is epilepsy. All symptoms seen in Alzheimer’s are thought to be due to the effects of a protein called beta-amyloid. Dr. Nygaard’s research will investigate the role of prion protein, a receptor for the beta-amyloid, in mediating seizures in Alzheimer’s disease. It is part of a comprehensive effort to understanding the role of prion protein in all symptoms of Alzheimer’s disease. There is currently no cure for this disease, and Dr. Nygaard’s research may help assess the prospect of targeting prion protein as a novel treatment strategy in Alzheimer’s disease.

Jing Qu, PhD
Postdoctoral Associate
The Salk Institute for Biological Studies

S-nitrosylation of Cdk5 in Alzheimer's Disease: cause or outcome?


Impairment of the enzyme Cdk5 has been implicated in neurodegenerative diseases, including Alzheimer’s disease. Through her research, Dr. Qu has discovered that Cdk5 in the brains of most Alzheimer’s afflicted patients underwent a protein modification process called nitrosylation. Dr. Qu will seek to identify the role that Cdk5 nitrosylation plays in the generation of Alzheimer’s. Evaluating the molecular mechanism of Cdk5 may reveal a new cause of Alzheimer’s disease as well as offer hope of a new cure.

Guido Stadler, PhD
Postdoctoral Fellow
University of Texas Southwestern Medical Center at Dallas

Telomere Position Effect in Facioscapulohumeral Muscular Dystrophy


Facioscapulohumeral Muscular Dystrophy (FSHD) is an inherited form of muscular dystrophy that progresses during aging, initially affects the skeletal muscles of the face, scapula, and upper arms. Although its genetic basis has been determined, the molecular mechanism of how this genetic defect translates into its characteristic disturbances of normal mechanical, physical, and biochemical functions remains an enigma. Dr. Stadler’s study will investigate the role of replicative aging and telomere length of skeletal muscle precursor cells in FSHD. While the mechanism has the potential to develop specific treatments for patients suffering from FSHD, it may also be important for “normal” aging and other age-related diseases.

Cagdas Tazearslan, PhD
Post-Doctoral Fellow
Albert Einstein College of Medicine

Insulin/IGF-1 signaling and human longevity


Reduced insulin/insulin-like growth factor-1 (IGF1) signaling (IIS) results in extension of lifespan in laboratory animal models. However, the impact of this evolutionarily conserved pathway on human longevity remains unclear. Dr. Tazearslan’s research aims to explore whether IIS plays a role in human longevity, and the results of this study may reveal an important role for IIS in longevity in human populations. Identification of IIS gene variants that promote longevity may provide a rational basis for intervention strategies that delay age-related diseases and promote healthy lifespan in people, thereby enhancing the quality of life in the elderly.

Dario Riccardo Valenzano, PhD
Stanford University

Genetic Mapping of the genes involved in longevity differences among populations of the short-lived fish Nothobranchius furzeri


The African fish, Nothobranchius furzeri, is the shortest known living vertebrate, a species that produces populations that dramatically differ in lifespan. Dr. Dario Riccardo Valenzano will investigate the N. furzeri’s entire genome, and seek to identify the causal genes involved in the longevity differences between long-lived and short-lived populations of the African fish. Results may not only reveal novel genes but also basic mechanisms that possibly play a similar role in other vertebrates.

Victor Van Laar, PhD
Associate Scholar
University of Pittsburgh

The role of parkin in neuronal mitochondrial dynamics and neurodegeneration

Photo and summary pending...

Jason Wood, PhD
Postdoctoral Research Assoc.
Brown University

The role of Sirt4 in regulating lifespan adn metabolism in Drosophila melanogaster


The Sirt4 gene, a member of the sirtuin gene family, has been implicated in the control of longevity and metabolism in a number of different organisms. Sirt4 is expressed in the mitochondria, an organelle that supplies cellular energy. Dr. Wood’s project seeks to better understand the link between mitochondrial function and aging, using the fruit fly Drosophila melanogaster as a model system. Results of his research may yield valuable insight about the role of Sirt4 in aging, metabolism, and mitochondrial function and thus, also a potential therapeutic target for ameliorating the age-related functional decline of mitochondria.

Yang Yang, PhD
Postdoctoral Associate
Yale University

Nicotinic Restoration of Prefrontal Cortex Physiology in Aged Monkeys


Aged monkeys, just like many older humans, have impairments in working memory. The prefrontal cortex is the most important brain area for this executive function, and networks of neurons in the prefrontal cortex must excite each other to sustain memories over a delay. Nicotinic receptors can be found on prefrontal cortex neurons near sites where these networks interconnect. Stimulation of nicotinic receptors by the neurotransmitter, acetylcholine, or by drugs that mimic acetylcholine, agonists such as nicotine, strengthens prefrontal network connections. Dr. Yang’s project will examine whether these nicotinic receptor agonists can improve working memory in aged monkeys with weak prefrontal cortical network connectivity. Positive results will have immediate clinical significance, suggesting these drugs may also provide a useful treatment for cognitive deficits in the elderly.