• December 20, 2012

    Grants Funded from RFA-AG-11-004, “Regional and International Differences in Health and Longevity at Older Ages (RFA-AG-11-004)”

    NIA published an RFA entitled “Regional and International Differences in Health and Longevity at Older Ages” on June 22, 2010 which solicited R01 applications to advance knowledge on the reasons behind the divergent trends that have been observed in health and longevity at older ages, both across industrialized/high life expectancy nations and across geographical areas in the U.S.

    NIA funded seven R01 applications from the RFA during the summer of 2011. Four grants are studying the underlying reasons for the large American health disadvantage at older ages compared to their Western European counterparts. These grants are focusing on issues including obesity, social policies addressing work-family strain, physiological dysregulation due to work stress, early life conditions such as childhood health, the impact of the recent financial crisis, and cancer screening rates.

    1. Lisa Berkman, Social protection, work and family strain: cumulative disadvantage effects in the US and Europe (R01 AG040248)
    2. Pierre-Carl Michaud, Working Lives, Physiological Dysregulation and International Health Differences (R01 AG040176)
    3. Samuel Preston, The Contribution of Obesity to International Differences in Longevity (R01 AG040212)
    4. James Patrick Smith, International Differences in Health, Longevity, and SES (R01 AG040165)

    Two grants focus on the U.S. The first is developing a new publicly-available database of historical mortality data by state which will be invaluable for future study of the driving forces behind US mortality trends. The second project is studying how US health disparities among different birth cohorts are related to US geographic region.

    1. Scott Lynch, Understanding US regional health & mortality disparities: A Life Course Approach (R01 AG040199)
    2. John Wilmoth, Variability of mortality levels and trends by state in the United States (R01 AG040245)

    Finally, NIA funded a one-year project studying the remarkable increase in life expectancy experienced by East Germans after the 1989-1990 unification of West and East Germany; the aim of this project is to understand the relative impact on increased life expectancy between the increased affluence experienced by East Germans vs. the improved health care system available to East German elderly post-unification.

    1. James Vaupel, Theory-Based Comparative Demography of Mortality at Older Ages (one-year project only on East-West Germany, R01 AG040050)

    (See below for the grant abstracts. Also, for more information on the above grants,
    go to the NIH RePORTER site at ).

    RFA-AG-11-004 was influenced by a National Academy of Sciences panel which determined, based on available evidence, that past smoking rates are a major reason for shorter lifespans in the US compared to other high-income countries, and that obesity rates in the US also appear to be a significant factor (see ). The summary report from the National Research Council, which also identified research gaps, is entitled Explaining Divergent Levels of Longevity in High Income Countries (NRC, 2011) and is available at . A volume of background scientific papers is entitled International Differences in Mortality at Older Ages (NRC, 2011) and is available at .


    Theory-Based Comparative Demography of Mortality at Older Ages

    DESCRIPTION (provided by applicant): Theory is important in guiding research to penetrate the bewildering surface of myriad age, sex, time and population-specific statistics about mortality at older ages. The goal of the proposed research is to advance theory and thereby empirical knowledge of mortality comparisons by using data from the "natural experiment" of East-West German unification and the resulting rapid convergence of E. German death rates to W. German levels to quantify the relative causal importance of two factors suggested by theory: "prosperity" vs. "healthcare".

    International Differences in Health, Longevity, and SES

    DESCRIPTION (provided by applicant): Our first objective examines impacts of early life conditions and childhood health across a set of European countries and the US on salient later life adult outcomes including adult health and socioeconomic status (SES). Differences in early life conditions are potentially an important source of international differences in adult health. Second, we will study dual pathways between SES and health with an emphasis on England and America. Pathways from SES to health are explored by examining whether future onsets of new chronic conditions using self-reports and biomarkers of disease are related to key SES markers- income, wealth, and education. We will examine whether ""innovations"" in economic status affect health-especially during the recent financial crisis. Health feedbacks to labor supply, income, and wealth may be quantitatively important. Health outcomes include physical and mental health, including depression, psycho-social health, overall well-being, and life satisfaction. Our third specific aim examines the relationship between alternative measures of SES and subsequent all cause and cause-specific incident mortality in England and the US. Access to financial resources may be essential in dealing with consequences of health problems after they occur. The final specific aim will examine whether differential cancer screening rates can account for significant parts of country differences in cancer rates, especially those to the disfavor of the United States. Screening is known to vary across types of cancer and is believed to be more aggressive for breast, colon, and prostate cancer in the US than the UK and low for respiratory cancer.

    PUBLIC HEALTH RELEVANCE: The research is important since it deals with the level of well-being of older people in the United States compared to the rest of the Industrialized Western World. By using comparative analysis of the United States, England, and other countries, we can assess how and why over-all well-being is related to health and socioeconomic status at older ages in these countries.

    Working Lives, Physiological Dysregulation and International Health Differences

    DESCRIPTION (provided by applicant): The U.S. appears to have worse health than people in a number of European countries. Because health reflects an accumulation of processes over a lifetime, we will study how stressful events during the working years may affect pre-retirement health and ultimately longevity. The broad aims of this application are to find whether in panel data the health gap between the U.S. and Europe increases during the working years, but not during the post-retirement years, and to explain these broad facts by differences in the stress induced in the labor market and by differences in the ameliorating effects of economic and social policy (including health insurance). Our analysis will use data on 15 countries, which provides a wealth of variation in institutions in time as well as in space. The principal outcomes will be fourfold. First, this study will clarify at what point in the life-cycle health differences emerge and chart their path thereafter. Second, this study will propose a formal economic and biological model linking indicators of physiological functioning to other health and economic outcomes clarifying some of the concepts measured in the literature and guide empirical work on the topic. Third, this study will provide micro as well as cross-country empirical evidence on the relationship between economic stressful events and physiological dysregulation using biomarkers but also reported health measures. Fourth, because of its cross-country design, this study will exploit differences in social policy across countries and over time to see estimate how these policies contribute to the international differences in health through the effect of physiological dysregulation on health.

    PUBLIC HEALTH RELEVANCE: The U.S. has fallen behind in terms of life expectancy in the pre-retirement years and large differences in health have emerged between the U.S. and Europe. This project aims to test the hypothesis that differences in physiological dysregulation due to a more stressful working life in the U.S. are responsible for those differences. This project will use a large array of longitudinal datasets in 15 countries to link health outcomes in the pre-retirement years to life histories and exploit differences in social policy across countries.

    Understanding US regional health & mortality disparities: A Life Course Approach

    DESCRIPTION (provided by applicant): Regional disparities in health and mortality in the U.S. have been observed repeatedly, but little attempt has been made to explain them. At best, anecdotal explanations are usually offered. For example, poorer health among southerners is often attributed to diet without any empirical support. Extant literature suffers from several additional shortcomings. First, many studies focus on a single health outcome, like stroke mortality, thereby underestimating the full extent of regional variation in health. Second, many studies measure region coarsely. Often, only one region is contrasted against all others. This approach also leads to underestimation of the full range of regional variation in health and hinders our ability to understand the precise mechanisms that account for it, because within-region cultural and structural heterogeneity is extensive. Third, studies of regional disparities have generally failed to take a life course perspective, instead treating them as existing in a temporal vacuum. The proposed research will address these shortcomings, first by adopting a life course perspective. The life course perspective recognizes that neither region of residence, nor health, nor the relationship between them, is static at the individual level across age. Furthermore, regional characteristics and the distribution of health outcomes also vary across sociohistoric time, implying that the relationship between region and health may differ across birth cohorts. The life course perspective therefore provides a more comprehensive and detailed lens through which to begin to explain regional differences in health. Given this perspective, the proposed research will establish the full extent of regional disparities in health using a variety of longitudinal statistical methods applied to at least three nationally-representative, large sample data sets: the General Social Survey, the Health and Retirement Study, and the National Health Epidemiologic Follow-up Surveys. These data will be augmented via the collection of region-year contextual variables like physician density, climate, etc. Collectively, these surveys contain a wide variety of health measures, including self-rated health, physical functioning, depressive symptoms, mortality, and diabetes, as well as refined measures of region (i.e., the nine-category Census measure). Importantly, these three surveys also contain at least one measure of region of residence in early life (birth and adolescence), which, from a life course perspective, is useful in helping differentiate the role of early life socialization into regional culture from the role of structural characteristics of an individual's current region of residence in influencing health. In addition, this early life region measure, as well as the use of longitudinal methods, will enable the investigation of the extent to which health influences regional mobility, an issue (i.e., endogeneity) commonly ignored in research. Basic descriptive methods, typical regression models, multistate life table methods for both panel and cross-sectional data, and hierarchical growth models, including autoregressive latent trajectory models, will be used to flesh out the extent of regional differences in health as well as the mechanisms that account for them.

    PUBLIC HEALTH RELEVANCE: Regional differences in health and mortality in the US have been observed in numerous studies but have been left largely unexplained. Understanding the mechanisms that account for regional differences is important for determining how health disparities can be reduced. Our proposed project aims to determine the full extent of regional differences in health and to explain them (1) by using more refined measures of region and a broader array of health outcomes than used in previous research, and (2) by employing a life course perspective and methods to differentiate with greater precision and accuracy the pathways via which region may affect health. 

    The Contribution of Obesity to International Differences in Longevity

    DESCRIPTION (provided by applicant): The primary objective of this research is to identify the contribution of obesity to international differences in longevity. Adults in the United States have a higher prevalence of obesity than adults in any other country in Europe, North America, or East Asia. At the same time, life expectancy in the United States has fallen below that of most other OECD countries and ranked 32nd in the world in 2008. One of the prime candidates to account for the US disadvantage in health and longevity is its high level of obesity. A key input to evaluating the contribution of obesity to international differences in longevity is the set of individual-level mortality risks associated with different levels of obesity. This project will identify the set of mortality risks associated with obesity that should be used in international and intertemporal comparisons. We do so by explicitly introducing two other factors on which the mortality risks associated with current obesity depend: an individual's history of obesity and his or her smoking status. The omission of obesity histories from earlier studies has led to biased estimates of the effects of current obesity. Non-smokers show a higher mortality risk from obesity than smokers, so that countries that smoke heavily should be expected to have lower risks from obesity. We will apply these sets of obesity risks to calculate population attributable risks and obesity's implications for survivorship and longevity. An important product of our work will be an explanation of the large declines that have been observed in the estimated effect of obesity on mortality. In addition, we will develop a new indirect approach to estimating the contribution of obesity to international differences in longevity by building on previous methods developed to estimate smoking-attributable mortality. Epidemiologic and demographic studies of obesity would benefit greatly from a clarification of the mortality risks associated with obesity. Such a clarification would also contribute to improved projections of mortality in the US and elsewhere. Uncertainty about future of mortality is the single factor to which fiscal balances in the Social Security Trust Fund are most sensitive. The contribution of this project to improved projections is enhanced by its explicit incorporation of obesity histories into the risk analysis, since these histories are revealed well in advance of actual mortality conditions.

    PUBLIC HEALTH RELEVANCE: The United States has the highest prevalence of obesity and one of the lowest life expectancies among developed nations. The objective of this research is to identify the contribution of obesity to international differences in longevity. Results will lead to improved mortality projections and a clearer understanding of how obesity is influencing national mortality profiles.

    Variability of mortality levels and trends by state in the United States

    DESCRIPTION (provided by applicant): The purpose of the project is to promote research on historical trends and, in particular, interstate variations in the mortality of the United States since the 1930s. To this end, we will construct a publicly-accessible collection of mortality data series by state, designed to meet the research needs of team members and collaborators as well as those of the greater academic community. The new data series will include indicators of both total (i.e., all causes of death) and cause-specific mortality. We will create state-level estimates of all-cause mortality by age, sex, and year for the period from 1933 to 2007. We will also create annual state-specific estimates of mortality by age, sex, and cause of death for 1959-2007 (possibly, 1950-1958 as well). All data series will have the same format used for country estimates in the Human Mortality Database (HMD,, helping to facilitate comparative research both within the United States and on an international level. This work will draw on data from various sources, including the vital registration system, the decennial census, and the beneficiary records of Social Security and Medicare. It will require the development of new methodologies for combining such information into coherent and comparable series of mortality estimates, including complete life tables. Our knowledge of the data sources, including their defects and limitations, will be clearly documented and distributed alongside the data within the HMD. The project is intended to catalyze research on mortality patterns and trends by state within the U.S. State-specific mortality data are intrinsically useful for the analysis of health disparities, since geographic differences are an important component of overall inequality in the face of death. The products of the work proposed here will facilitate more detailed analyses of regional mortality differentials by cause within the U.S., which could offer new insights and evidence about the driving forces behind the country's mortality trends in recent decades - in particular the slow pace of decline compared to other high-income nations, especially for women.

    PUBLIC HEALTH RELEVANCE: The purpose of the project is to construct a publicly-accessible collection of mortality data series by state since the earliest time available until now (1933-2008). Improved information about mortality patterns by sex, age groups and causes of death contributing to the ongoing disparities in life expectancy across U.S. states will help researchers to identify the underlying conditions and processes that have produced these patterns. A better understanding of geographic differences in U.S. mortality will be a useful tool for guiding future policy efforts to improve the health and longevity of the population and to investigate the historical impact of public health interventions.

    Social protection, work and family strain: disadvantage effects in US and Europe

    DESCRIPTION (provided by applicant): The United States is losing ground in health: our ranking in life expectancy is near the bottom of European countries and comparisons of major chronic conditions in the US and 13 European countries showed the US to have higher disease prevalence than any comparison country. The diverging life expectancy (LE) trends have been most distinct for American women, but the US also fares poorly with regard to male life expectancy and infant mortality. The health gap is largest among socioeconomically disadvantaged groups, but even well- educated Americans have worse health than many of Europeans. We hypothesize that the explanations for the American health disadvantage have roots in the challenging social context faced by families, and in particular women, in post-WWII America. Since WWII, American society has been marked by: high fertility; high female labor market participation; weak labor laws and family protection policies; and family instability, and increased single parenthood. The combination or convergence of these factors created a ""perfect storm"" that threatened vulnerable families and imposed extreme stresses even on the relatively advantaged. Such social conditions might work via influencing health behaviors or through more direct physiological mechanisms. We have developed a theoretical framework for this confluence of conditions that builds on the job strain models incorporating dimensions of demand, control and support but adds an important dimension related to family that extends the strain model beyond work to family life. Over time Americans, especially women, have experienced high demands in terms of full time work often with high family demands, coupled with low formal support ( social protection policies) or informal support from other family members. This combination especially among workers with low job control leads to a cumulative disadvantage taking its toll in health over time. In order to understand whether these social conditions account for cross area variations in risk we must understand whether either the distribution and/or the toxicity of the ""risk"" vary across areas. We draw from ongoing studies including HRS, SHARE and ELSA, mortality data at a country level (using the human mortality files) and data on public policies, collected from the CPS,SIPP and SHARELIFE and OECD. We propose 4 specific aims: Aim 1: Describe the distribution of work-family strain for females born 1920-1960, across the US and EU. Aim 2: Assess the differential toxicity of work-family strain on CVD risk behaviors and biomarkers, incidence of stroke and heart disease, CVD mortality, and life expectancy in the US and Europe. Aim 3: Assess whether distributions or the toxicity of work-family strain explain geographic and temporal variations in CVD and life expectancy. Aim 4: Assess impacts of trends in work-family strain on socioeconomic inequalities in mortality in the US and Europe.

    PUBLIC HEALTH RELEVANCE: With the vast majority of women in the labor force who also have young children and with the aging of societies virtually across the globe, there is an urgent public health need to provide both formal (policy) and informal (family) support to women and their families. Evidence suggests that work family strain has an adverse impact on health outcomes for low wage employees and young children and perhaps other groups. Countries in which a number of work family policies have been implemented seem to fewer adverse population health outcomes. This situation is particularly severe in the US where fertility and labor force participation among women is high and where state and federal policies promoting the health of families is very limited.

    Prepared December 2012

  • December 12, 2012

    The human brain is made up of tens of billions of neurons, brain cells that act as information messengers, transmitting and receiving chemical and electrical signals. These messages are received by branch-like cell structures called dendrites after traveling across synapses, the tiny gap between neurons. Now, researchers in NIA’s Intramural Research Program have shown in mice that a protein, PGC-1alpha, may play an important role in forming and maintaining healthy dendrites and synapses in the hippocampus--the brain region important to learning and memory. The findings are reported online in the Dec. 4, 2012, issue of Nature Communications.

    PGC-1alpha protein acts by stimulating the proliferation of mitochondria, the “powerhouses” of the cell that generate energy needed for the cell to function and survive. In cultured rat hippocampal neurons, the process resulted in increased numbers of dendrite spines; knocking out the protein not only reduced the number but also the thickness of the spines. The NIA investigators also found that brain-derived neurotrophic factor (BDNF), which is involved in learning and memory and may protect neurons against degeneration, stimulated the production of PGC-1alpha and mitochondrial activity in adult mice.

    Because BDNF is believed to play a key role in beneficial effects of exercise and cognitive stimulation on brain health, this suggests a role for PGC-1alpha and mitochondria in healthy brain function. Further study is needed to determine if PGC-1alpha may be a promising therapeutic target for Alzheimer’s disease and other neurodegenerative disorders.

    Reference: Cheng, A. et al. Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines. Nature Communications 3:1250. doi:10.1038/ncomms2238 2012


  • December 7, 2012

    Two new studies by NIA-funded researchers at UCLA have shown that older people are less adept than younger people at discerning visual clues of dishonesty in others. This may help to explain why many older people are more susceptible to financial fraud and other scams, the researchers found. Research results appeared online December 3, 2012, in the Proceedings of the National Academy of Sciences.

    In the first study, investigators had 119 older adult (average age 68) and 24 younger adults (average age 23) look at 30 photographs of faces and rated them on how trustworthy and approachable they seemed. The faces were intentionally selected to look trustworthy, neutral, or untrustworthy.

    Both groups reacted similarly to the trustworthy and neutral faces. But, younger adults reacted strongly to the untrustworthy faces, while the older adults did not. The older adults saw these faces as more trustworthy and more approachable than the younger adults.

    In the second study, 23 older adults (average age 66) and 21 younger adults (average age 33) underwent functional magnetic resonance imaging brain scans while looking at the faces. The brains of the younger adults showed activity in the anterior insula region both when they were rating the faces and especially when viewing the untrustworthy faces. In contrast, the older adults displayed very little anterior insula activation during the imaging. The anterior insula is associated with “gut feelings,” which represent expected risk and predict risk-avoidance behaviors.

    These studies are the first to show age differences in a characteristic pattern of brain activation in a "social" situation involving the assessment of another person's trustworthiness. Additional research is needed to determine whether the results are caused by age-related changes in the brain or if older adults are simply less motivated to look for social signals of untrustworthiness.

    Reference: Castle, Elizabeth, et al. Neural and behavioral bases of age differences in perceptions of trust. Proceedings of the National Academy of Sciences. Published online December 3, 2012,

  • November 15, 2012

    Two international teams of researchers, with NIH scientists and support, have separately identified a rare variation in the TREM2 gene as a moderate risk factor for late-onset Alzheimer’s disease. TREM2 is a gene involved in inflammation and immune response, and this discovery provides an important clue for researchers seeking a better understanding of the Alzheimer’s disease process. Researchers have hypothesized for many years that a rare genetic variant can confer moderate risk for disease. These are the first studies to identify such a variant related to Alzheimer’s disease.

    The first group was led by John Hardy, Ph.D., of University College London (UCL) Institute of Neurology and at NIH by Andrew Singleton, Ph.D., of the NIA. The second team was led by deCODE Genetics, Reykjavik, Iceland, whose work was supported in part by NIH.

    The approach taken to find this gene variant suggests that a similar research strategy should help identify additional variants of this type. The researchers in the UCL group used genome, exome and Sanger sequencing to analyze the genetic variability of TREM2 in 988 people with Alzheimer’s disease and 1,004 normal participants. They performed a meta-analysis of genome-wide association studies for Alzheimer’s and tested brain tissues from deceased Alzheimer’s patients. They also compared TREM2 gene expression in a transgenic mouse model of the disease.

    The deCODE group obtained genome sequences from 2,261 Icelanders and identified sequence variations considered likely to affect protein function. They replicated their finding in a cohort from the NIA-supported Alzheimer’s Disease Research Center at Emory University, Atlanta, as well as in population groups in Norway, the Netherlands, and Germany.


    Guerriero R, et al. TREM2 Variants in Alzheimer’s Disease. New England Journal of Medicine. Published online, November 14, 2012.

    Jonsson T, et al. Variant of TREM2 Associated with the Risk of Alzheimer’s Disease New England Journal of Medicine. Published online, November 14, 2012.

  • November 14, 2012

    An international team of researchers has found that the vitamin D receptor gene (VDR), which senses and communicates the presence of vitamin D to the body, influences the chance that people with vitamin D deficiency develop negative health outcomes. Some variants of VDR may have a protective effect, while others might increase these people’s predisposition for the outcomes, specifically hip fracture, heart attack, cancer, and even death. This finding helps explain why some people with vitamin D deficiency have few health issues and others have life-threatening complications. The study was published online in The Journal of the American Medical Association on November 14, 2012.

    Researchers involved in the study, which was supported in part by several components of the NIH, including the NIA, National Heart, Lung, and Blood Institute (NHLBI), National Institute for Neurological Disorders and Stroke, the National Center for Advancing Translational Sciences, and National Institute of Diabetes and Digestive and Kidney Diseases, suggest that understanding the underlying genetic characteristics related to vitamin D metabolism may ultimately help move treatment closer to a personalized and more effective approach. For instance, if a gene is preventing the body from using the little vitamin D it has, vitamin D supplements might not help avoid adverse outcomes.

    Scientists analyzed data from participants of NHLBI’s Cardiovascular Health Study (CHS); NIA’s Health, Aging, and Body Composition (Health ABC) study; the Invecchiare in Chianti (InChianti) study in Italy; and the Uppsala Longitudinal Study of Adult Men (ULSAM) in Sweden.

    Reference: Levin GP, et al. Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical Outcomes. JAMA.Published online November 14, 2012.

  • October 25, 2012

    A team of NIH-supported researchers has confirmed a link between age-related hearing loss and a gene producing a key protein in the inner ear. The findings reinforce observations in older people that genetics and environment interact, linking age-related hearing loss to other neurodegenerative risk factors. Results of the nine-year study were published online on October 25, 2012, in Hearing Research.

    The study confirms the genetic association and, for the first time, establishes a link between a gene and difficulties with speech perception in older people. Previous research in a large group of older adults in Europe had identified a significant risk factor associated with age-related hearing impairment (ARHI) in the glutamate metabotrophic receptor 7 (GRM7) gene.

    The research team analyzed data from 687 individuals (59 percent female) from the Rochester, New York, greater metropolitan area. All study participants were white, with an average age of 71 and not related to anyone else in the study. Participants had a wide range of hearing abilities and underwent extensive standard and specialized assessments of hearing. Importantly, the researchers conducted tests of speech reception thresholds (SRTs) as well as pure-tone thresholds (PTs). DNA was taken from blood or tissue samples.

    Clinically, PTs are used to measure the basic level of hearing ability and sensitivity to sounds. But they do not indicate how well a person can perceive and process speech, which is a significant problem for older people with hearing loss. Deficits in speech detection can detract from productivity, quality of life, and psychological well-being for older people.

    The study results show that GRM7 is significantly associated with PT and SRT. This is the first investigation of genetic associations with measures of speech perception in older adults, supporting the role of GRM7 contributing to age-related hearing loss and speech perception.

    ARHI, also known as presbycusis, is one of the top three chronic medical conditions of older people, along with high blood pressure, and arthritis. More than 37 percent of people 65 and older report some trouble hearing; this increases to almost 59 percent in people 85 and older. Many older people find it difficult to adapt to hearing loss; this can result in communication difficulties at work and at home, leading to psychological problems, isolation and depression.

    Reference: Newman DL, et al. GRM7 variants associated with age-related hearing loss based on auditory perception, Hearing Research (2012).

  • October 12, 2012

    What:              Seminar, Dr. Jie Shen, Harvard Medical School, Boston

    When:             Thursday November 1, 2012, 12:00 PM – 1:00 PM

    Where:             Lipsett Auditorium, Building 10, NIH

    Title:                “Mechanisms of Age-Dependent Neurodegeneration in Alzheimer’s and Parkinson’s Diseases”

    The Geroscience Interest Group (GSIG) cordially invites you to the seminar listed above. Dr. Shen is a Professor of Neurology at Harvard Medical School and Brigham and Women’s Hospital in Boston, Massachusetts. Her research interests focus on the physiological functions of gene products responsible for familial forms of Alzheimer’s disease (AD) and Parkinson’s disease (PD) in relevant neural circuits in the adult brain, and how disease-causing mutations in these gene products lead to age-dependent circuit dysfunction and neurodegeneration. Her laboratory has been the first to generate and analyze gene-targeted mice modeling loss of function for many of these familial AD and PD gene products. Through multidisciplinary investigations combining brain circuit-specific knockouts with electrophysiological and behavioral analyses, her group has uncovered essential roles for Presenilins in neurotransmitter release and neuronal survival in the adult brain. Her proposal that loss of Presenilin function in the adult brain may underlie dementia and neurodegeneration in familial AD, termed the “Presenilin hypothesis”, has been particularly influential and has garnered considerable media attention. In addition, her studies of familial PD genes have suggested that impairments in autophagy and mitochondrial function may be mechanistic precursors of dopaminergic neuronal dysfunction and degeneration.

    The Geroscience Interest Group (GSIG) is a newly formed trans-NIH group aimed at enhancing opportunities for discussion of the intersection between the biology of aging and the biology of diseases and conditions that are of interest across ICs.   It is focused on basic biology, but with a longer view towards translation. If you are interested in learning more, please visit the GSIG web site ( ).

    The seminar will be videocast at and archived in the GSIG web site. Sign language interpretation will be provided. Individuals with disabilities who need reasonable accommodation to participate may contact Dr. Felipe Sierra at or at 301.496.6402.

  • October 10, 2012

    NIH, Alzheimer’s Association invite research funders to participate

    A new, publicly available database is seeking to capture the full spectrum of current Alzheimer’s disease research investments and resources—both in the U.S. and internationally. The International Alzheimer’s Disease Research Portfolio (IADRP), developed by the National Institute on Aging (NIA), part of the NIH, in collaboration with the Alzheimer’s Association, will enable public and private funders of Alzheimer’s research to coordinate research planning, leverage resources, avoid duplication of funding efforts and identify new opportunities in promising areas of growth. The newly developed resource, currently hosted and maintained by NIA, helps to implement research goals of the National Plan to Address Alzheimer’s Disease (NAPA), announced by Health and Human Services Secretary Kathleen Sebelius in May 2012.

    “We need to do everything we can to find new, more effective ways to prevent and treat Alzheimer’s, and the research community recognizes the urgent need to coordinate funding strategies and leverage resources in order to maximize our effectiveness,” said NIA Director Richard J. Hodes, M.D. “We invite all private and public funders of Alzheimer’s research— federal and international funding agencies, academia, and privately funded researchers in the U.S. and throughout the world—to join us in building this new resource.”

    “Researchers and funders seeking scientific opportunities can use this database to inform their own efforts by searching for research being conducted on specific topics, to track research patterns over time, and to compare research areas supported by different funders,” Hodes said. He noted it will also provide the public a more complete picture of the scale of ongoing research into the causes and possible treatment and prevention of the disease.

    The IADRP uses the Common Alzheimer’s Disease Research Ontology (CADRO), a three-tier classification system created to include the complete range of Alzheimer’s disease research and related resources. The CADRO, developed in collaboration by the NIA and the Alzheimer’s Association, is organized around seven categories:  Molecular Pathogenesis and Physiology of Alzheimer’s Disease; Diagnosis, Assessment and Disease Monitoring; Translational Research and Clinical Interventions; Epidemiology; Care, Support and Health Economics of Alzheimer’s Disease; Research Resources; and Consortia and Public-Private Partnerships.   

    “In order to capture and compare the wide array of existing investments in Alzheimer’s research, funding organizations needed a common language and a common classification system. The CADRO provides this common language,” said Lorenzo Refolo, Ph.D., of NIA’s Division of Neuroscience, one of the developers of the ontology and the IADRP database

    “As nations around the world prepare for a significant increase in Alzheimer's prevalence, efforts are intensifying to better understand the natural history and progression of the disease and develop new approaches for diagnosis, treatment and prevention,” said William Thies, Ph.D., Alzheimer’s Association chief medical and scientific officer.

    “This database is a powerful tool for research funders to evaluate their existing research portfolios and become more strategic in their future funding by identifying gaps, overlaps, redundancies, but also to identify emerging opportunities. It will help funding organizations focus their commitments to underfunded areas of research and identify unexplored research potential. The goal is to get the answers we need faster,” Thies said.

    NAPA required the U.S. to develop a national plan for research, care and services needed to address Alzheimer’s. Under the plan, announced May 15, 2012, the primary research goal calls for preventing and effectively treating the disease by 2025. Toward that end, the plan identifies the coordination of research with international public and private entities as a vital strategy towards accelerating the discovery of effective treatments (see Strategy 1.D under Goal 1 (PDF, 965K)). The IADRP database, a product of a two-year long collaborative effort between the NIA and the Alzheimer’s Association, is a major step towards the implementation of this strategic goal.

    Along with NIA, over 20 fellow NIH Institutes and Centers are part of the database. Other federal agencies participating in the effort include the Agency for Healthcare Research and Quality, Centers for Disease Control and Prevention, Administration on Aging, the Department of Veterans Affairs and Department of Defense. The Alzheimer’s Research UK is the first international entity to join the collaboration.

    IADRP can be found at  For more information, contact Dr. Lorenzo Refolo, NIA Division of Neuroscience, at 301-496-9350 or; or, Dr. Heather Snyder, Alzheimer's Association, Medical and Scientific Relations Division, at 312-335-5184 or


    The Alzheimer's Association is the world’s leading voluntary health organization in Alzheimer’s care, support and research. For more information on the Association, visit

    The National Institute on Aging, part of the NIH, leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. The NIA provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer’s Disease Education and Referral (ADEAR) Center at For more on health and on aging generally, go to To sign up for e-mail alerts about new findings or publications, please visit either website.

    About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

    NIH …Turning Discovery Into Health

  • October 2, 2012

    Neil BuckholtzThe National Institute on Aging is pleased to announce that Neil Buckholtz, Ph.D., has been appointed as the new Director of the Division of Neuroscience (DN). Dr. Buckholtz comes to this position after 19 years of distinguished leadership as chief of the Dementias of Aging Branch in DN.

    “Dr. Buckholtz’s experience in the development, coordination and implementation of basic and clinical Alzheimer’s research will be a tremendous asset at this critical juncture in research on cognition, Alzheimer’s and aging,” said NIA Director Richard J. Hodes.

    Dr. Buckholtz and colleagues led the successful NIH/HHS Alzheimer’s Disease Research Summit held in May, Hodes noted. At the Summit, HHS Secretary Kathleen Sebelius introduced the Nation’s first National Plan to Address Alzheimer’s Disease which placed NIA at the forefront of its research effort. The Summit resulted in recommendations that are already guiding NIH and others in the field. Dr. Buckholtz is well known for his creativity and determination as a driving force behind the Alzheimer’s Disease Neuroimaging Initiative, which has become a model for public private partnerships in science and data sharing in neuroscience and other fields.

    “I look forward to Neil’s continued innovative thinking and problem-solving as we tackle important challenges of an aging population,” Hodes said.

    Dr. Buckholtz holds a doctorate in physiological psychology from the University of Wisconsin, Madison and was a faculty member at the Medical University of South Carolina, Department of Psychiatry, from 1970-1983, before coming to NIH. 

  • September 11, 2012

    NCI is Participating in PA-12-271, Potential Effects of Metformin on Aging and Age-Related Conditions: Small-Scale Clinical Studies and Secondary Analysis of Controlled Clinical Studies (R01).

    This Notice is to inform potential applicants that the National Cancer Institute (NCI) of the National Institutes of Health (NIH) has joined PA-12-271, entitled “Potential Effects of Metformin on Aging and Age-Related Conditions: Small-Scale Clinical Studies and Secondary Analysis of Controlled Clinical Studies (R01).”

    Additional information is available at