• 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

  • September 4, 2012

    Participation of NCCAM in RFA-AG-13-003: Secondary Analyses of Comparative Effectiveness, Health Outcomes and Costs in Persons with Multiple Chronic Conditions (R21)
    National Center for Complementary and Alternative Medicine

    The purpose of this Notice is to inform applicants that the NCCAM will participate, effective immediately, in the following NIH Funding Opportunity Announcement (FOA):

    RFA-AG-13-003: Secondary Analyses of Comparative Effectiveness, Health Outcomes and Costs in Persons with Multiple Chronic Conditions (R21). For this FOA, the following goals are of interest to NCCAM:

    • To assess the public health and health cost impact of complementary health approaches in individuals with two or more conditions,
    • To identify potential differences in effectiveness and safety of different complementary or integrative treatment regimens for patients with specific combinations of two or more conditions,
    • To examine alterations in safety or effectiveness of a complementary or integrative treatment for one condition related to the presence of one or more specific coexisting condition.

    NCCAM is interested in meritorious applications responsive to this FOA that fall within its scientific mission. NCCAM intends to commit up to $400,000 total costs in FY 2013. We encourage applications to conduct secondary analyses in datasets that have collected information on the use of complementary or integrative health approaches in individuals with multiple chronic conditions. We are also interested in applications that assess the impact or outcome of utilization of complementary or integrative health approaches.  To facilitate secondary data analyses, NCCAM has posted a list datasets (PDF, 89K) that contain this information.

    Examples of specific research questions or projects of interest to NCCAM include but are not limited to:

    • Evaluation of the impact of specific forms of complementary health care utilization on health outcomes or quality of life in individuals living with HIV or AIDS in addition to at least one other condition (e.g. pain, insomnia, etc).
    • Studies assessing the effect of complementary or integrative medicine use in individuals with chronic pain and sleep difficulties.
    • Examination of whether utilization of complementary or integrative approaches in patients with chronic pain and another health condition impacts utilization of pain medications.

    All other aspects of this FOA remain unchanged.