IOA Pilot Research Grantees 2009
Once again this year, thanks to the generous support of The Bingham Trust, the IOA was able to award 8 full Pilot Research Grants in support of aging and aging-related disease research. Congratulations to this year's awardees.
This year's Pilot Research Grant Awardees are as follows:
Hillary R. Bogner, MD, MSCE, Penn School of Medicine
Nalaka S. Gooneratne, MD, Penn School of Medicine
Michael Granato, PhD, Penn School of Medicine
Frank S. Lee, MD, PhD, Penn School of Medicine
Robert L. Mauck, PhD, Penn School of Medicine
Giang T. Nguyen, MD, MPH, MSCE, Penn School of Medicine
Richard M. Schultz, PhD, Penn School of Arts and Sciences
Rachel Werner, MD, PhD, Penn School of Medicine
- Hillary R. Bogner, MD, MSCE
"Integrating Depression Services into Type 2 Diabetes Mellitus Management"
Many older patients do not take their medications for Type 2 diabetes mellitus (DM) as prescribed by their physician. Depression is common among patients with Type 2 DM and may be the reason why patients do not take their medications as prescribed. A program in which Type 2 DM and depression are treated together in primary care would improve the health of older patients with both Type 2 diabetes and depression and would be practical in real world practices with competing demands for limited resources. There is an urgent need for research that can bring potentially life-extending strategies to older patients with both diabetes and depression. People can better control their Type 2 DM if they treat their depression and the same strategies can be used to help patients take their medications for both conditions. In this program patients would be involved in identifying problems with taking their medicines and working on solutions. The aims of this program would be to improve how patients take their medications for Type 2 DM and depression as well as blood glucose control and symptoms of depression over 3 months. To see whether this program works we will compare the results of patients receiving this program to those who do not receive the program. Findings may lead to the development of other programs in which depression and chronic medical conditions are treated together.
- Nalaka S. Gooneratne, MD
"A Novel Method for the Early Detection of Delirium in Hospitalized Patients with Cognitive Impairment Using Wrist and Ankle Accelerometry"
Delirium is a common problem that affects older adults with cognitive impairment when they are hospitalized. It is described as a fluctuating level of alertness/awareness that is often characterized by confusion and disorientation. It can be very stressful for the patient, their caregiver, and the health care staff because it can interfere with proper patient care. Early identification of delirium is very challenging because older adults with cognitive impairment may not be able to accurately report their symptoms. The major goal of this project is to determine if abnormal rest-activity patterns, such as increased activity during the sleep period, can be used to identify a pre-delirium state in older adults with cognitive impairment during the course of their hospitalization. We plan to use a small wrist-worn device to monitor a patient’s activity level and identify periods of high and low activity. We will then analyze this information using a variety of mathematical equations to see if one can effectively identify a pre-delirium state. Detection of this pre-delirium state could then allow for earlier treatment of delirium, which in turn could significantly reduce the risk of hospital complications when older adults with cognitive impairment are hospitalized.
- Michael Granato, PhD
"Zebrafish as a Model for Peripheral Nerve Regeneration"
Patients with traumatic peripheral nerve and spinal cord injuries (40 per million population) require extensive medical treatments, and with an aging population and changing demographics these numbers are expected to skyrocket. Even for injuries to peripheral nerves, where the potential of regeneration is retained, the frequent lack of a favorable functional outcome remains an important clinical problem. This is based in part on the fact that nerve regeneration is a complicated process that involves many cellular mechanisms, including local neurite degeneration, neurite outgrowth/guidance, and synapse formation just to name a few. We propose to generate a universal tool kit to visualize (and ultimately manipulate), in living zebrafish larvae and in real-time, the cellular and subcellular events that take place during nerve degeneration and regeneration. This will establish a powerful model in which to study.
- Frank S. Lee, MD, PhD
"Targeting Prolyl Hydroxylase to Treat Anemia in the Aging"
Anemia (low red blood cell mass) is a common clinical condition observed in the aging population, and is accompanied by significant morbidity. It has been estimated that 10% of the population 65 years and older is anemic. Understanding the mechanism by which red blood cell mass is regulated may lead to novel means to treat this important condition. A molecular pathway has recently been described in which a protein called PHD2 has been proposed to control red blood cell mass. In young mice, decreasing PHD2 levels by a method known as conditional knockout increases red blood cell mass. Whether this response occurs in aging mice is not known. We will test whether decreasing PHD2 levels in aging mice changes red blood cell mass. We anticipate this study will provide important information for evaluating whether targeting this pathway will afford a potential means to treat anemia in the aging population.
- Robert L. Mauck, PhD
"Age-Dependence of Functional ECM Formation by MSCs for Cartilage Regeneration"
Articular cartilage lines the surfaces of joints and transmits forces generated with physiologic motion. Although this unique tissue may function well over a lifetime of use, acute trauma or alterations in joint kinematics can disrupt tissue homeostasis and lead to degenerative changes. As the adult tissue has limited healing capacity, these degenerative changes result in cumulative erosion of the articular layer, a condition termed osteoarthritis (OA). OA affects more than 21 million people in the United States, including more than 1/3rd of the population over the age of 65. One evolving repair strategy combines chondrocytes (the cells within cartilage) with 3D scaffolds to enable in vitro tissue development. This “tissue engineering” (TE) approach generates replacement constructs that possess biochemical and histological features similar to the native tissue. In addition to chondrocytes, mesenchymal stem cells (MSCs) have been used to populate these same scaffolds. These multi-potential progenitor cells, isolated from bone marrow, can be induced to differentiate into a chondrocyte-like cell and deposit a cartilage-specific extracellular matrix (ECM). As the primary role of the native tissue is load bearing, TE constructs generated from either cell type must possess mechanical properties similar to that of the native tissue. Most cartilage TE studies have employed chondrocytes derived from juvenile tissues and few studies have addressed the important relationship between cell age and construct maturation. Recent studies have demonstrated a decline in chondrocyte yield, expansion, and matrix forming capacity when seeded in a TE construct for adult compared to juvenile cells. Further, the potential of MSCs to form tissues with cartilaginous compressive properties comparable to that achieved with primary chondrocytes remains to be determined. In this proposal we address these issues by evaluating the molecular, histological, biochemical, and mechanical features of engineered cartilage formed from fetal, juvenile, and adult chondrocytes and MSCs seeded in a 3D environment. These data will further define the process of neo-cartilage formation as a function of cell type and aging, and will establish new directions in regenerative medicine strategies for cartilage repair.
- Giang T. Nguyen, MD, MPH, MSCE
"Community Connectedness and Depression among Southeast Asian Immigrants in Late Life"
Depression in late life is an area of growing research, and studies addressing the determinants of geriatric depression among Asian Americans are lacking. At the same time, Southeast Asian immigrants and refugees are at particular risk for depression, because of the circumstances surrounding their migration from their countries of origin. Unlike many other Asian Americans, Southeast Asians suffer from particularly high levels of health and socioeconomic disparities. Anecdotal evidence suggests that social, linguistic, and cultural isolation plays an important role in the mental health of Southeast Asian immigrant elders. The proposed study uses a Community-Based Participatory Research approach by partnering with a local community-based organization serving (and run by) Southeast Asians. We will assess depressive symptoms and relate these with measures of social connectedness and other demographic characteristics in the underserved and understudied population of Southeast Asian immigrants in late life. We will focus on linguistically isolated Vietnamese and Laotian elders. The preliminary data to be obtained will aid in the development of larger studies and interventions to address depression among older Southeast Asian immigrants.
- Richard M. Schultz, PhD
"Live Imaging of Aged-Induced Aneuploidy during Meiosis in Mouse Oocytes"
What constitutes a high-quality egg is a holy grail in reproductive science. Although little is known about how a good egg is generated, minimally it must contain the appropriate chromosome content. An increase in aneuploidy is a major cause for the marked decline in human female fertility commencing at 35 years-of-age. The incidence of aneuploidy in eggs from women in their 20s is ~2%, but dramatically increases to 35% around 40 years-of-age, and is likely to be even higher because the source of a spontaneous abortion due to aneuploidy is frequently not recognized. Aneuploidy is a leading cause of pregnancy loss, and when development goes to term, an aggravating source of developmental disabilities and mental retardation, e.g., trisomy 21. Most aneuplodies associated with increased maternal age are due to non-disjunction and meiotic errors that occur during meiosis. Remarkably, the underlying molecular mechanisms that lead to the age-associated increase in aneuploidy are poorly understood. Results of our previous studies suggest that defects in the spindle assembly checkpoint (SAC) and kinetochore function are likely causes for the age-associated increase in aneuploidy. Eukaryotic cells have evolved highly conserved mechanisms to ensure that that chromosomes attach correctly to the spindle prior to anaphase onset. The SAC is one pathway that prevents segregation errors by blocking the onset of anaphase until all chromosomes make proper attachments. Using mouse as a model system together with imaging of live individual oocytes, we will test the hypothesis that the robustness of the SAC in oocytes decreases with age.
- Rachel Werner, MD, PhD
"Nursing Home Pay-for-Performance in State
Poor quality of nursing home care has been pervasive for decades and major national efforts have been launched to improve the quality of nursing home care. Increasingly, state Medicaid programs are adopting pay-for-performance incentives to improve quality of nursing home care. However, the extent to which states have adopted pay-for-performance and the structure of these pay-for-performance incentives is unknown. This project aims to investigate the extent of adoption of nursing home pay-for-performance by state Medicaid agencies across the country and to describe the structure of those pay-for-performance programs that have been implemented. This project is the first step toward a large-scale evaluation of the impact of pay-for-performance on nursing home quality of care.