• July 13, 2012

    On July 12, all of the seats in the Masur Auditorium were filled for the meeting of the NIA’s Geroscience Interest Group (GSIG), a newly formed trans-NIH interest group focused on the premise that aging biology is at the base of many of the chronic diseases that form significant portions of the research portfolios of most NIH Institutes and Centers.

    The full house was no surprise: The featured speaker was NIH Director Dr. Francis Collins. Dr. Collins described his research on Hutchinson Gilford Progeria Syndrome (HGPS), as well as its relevance to understanding normal aging. “It has been an amazing journey, moving very rapidly from gene discovery to clinical trials,” said Dr. Collins. HGPS is an extremely rare disorder characterized by exceptionally accelerated aging, leading to premature death at an average age of 13 years, usually from cardiovascular complications.

    Dr. Collins’ journey in this field started when, as a young physician, he was put in charge of Meg, a “real spitfire” of a young lady, he says, who was affected by the disease. His interest in HGPS was reawakened many years later when he was approached by Dr. Leslie Gordon of the Progeria Research Foundation, whose son Sam also has HGPS.

    Sparked by his encounter with Sam and others with HGPS, Dr. Collins’ laboratory put their interest into action, and in 2003 identified a single point mutation responsible for the syndrome, a silent mutation (G608G) in the gene coding for lamin A, a structural component of the nuclear envelope. Further molecular studies revealed that the mutation caused increased activation of a silent splice site, leading to the production of a truncated lamin A molecule termed progerin. Based on detailed knowledge of the biology of lamins and on his own research, Dr. Collins and his team were able to rapidly move the field toward translation so that within 5 years, a clinical trial for HGPS was begun, and, today, a second clinical trial is currently being considered.

    This is good news for the affected children and their families, who now have hope for management of HGPS. But the interest in HGPS goes beyond the disease itself. While viewed as an accelerated aging syndrome, many investigators in the aging research community have not thought these syndromes to faithfully represent normal aging. Aware of this view, Dr. Collins gave evidence of the potential for HGPS research to inform basic aging research. Not only is progerin produced by normal cells during aging, he noted, but abnormal splicing appears to be a common feature of aging, especially in cells that reach senescence via telomere loss.

    Dr. Collins is currently collaborating with NIA Director Dr. Richard Hodes, an expert in telomere biology who conducts research in his laboratory at the National Cancer Institute, to further pursue this area of research.

    “The seminar demonstrated the power of genetic and basic biology approaches not only to provide hope to individuals with rare diseases, but also to inform more common issues, including normal aging. I’m excited about the collaboration our labs have recently initiated,” said Dr. Hodes.

    During a discussion with the GSIG Executive Committee after the seminar, both Drs. Collins and Hodes reinforced their hope that this group could become a major force in trans-NIH efforts.

    “Aging biology has reached a tipping point for research,” said Dr. Felipe Sierra, GSIG founder and director of NIA’s Division of Aging Biology. “We have recent evidence that the aging process is malleable and it has been observed in several animal models that—when aging is delayed—so are the diseases and disabilities that normally accompany aging.”

    For more information on GSIG, contact Dr. Sierra at

  • June 30, 2012

    Despite efforts over many years to develop the biomedical science workforce pipeline for underrepresented minorities, results have been disappointing. In response to this unacceptable status quo, highlighted in a devastating description of the lack of progress in an August 19, 2011, report in Science, the NIH Director charged his Advisory Committee to the Director to form a special Diversity in Biomedical Research Working Group to see how NIH could devise a more effective plan to diversity the research workforce.

    On June 13, 2012, the Working Group offered its report and recommendations. The group focused on five key transition points in the pipeline from entry into graduate school to receipt of first independent research funding to awarding of tenure at an academic position or equivalent in an industrial setting. It offered 13 recommendations in five broad areas: data collection/evaluation; mentoring/career preparation and retention; institutional support; bias‐related research and intervention testing; and NIH diversity strategy and infrastructure. The executive summary and the full report are available at

    “The face of America is becoming more diverse and the biomedical workforce needs to reflect that diversity,” said NIA Deputy Director Dr. Marie Bernard, “NIA is committed to helping to achieve this, participating in a number of NIH-wide diversity programs and supporting two training programs unique to NIA.”

    See more information for prospective grantees about NIH programs to diversify the research workforce.

  • June 1, 2012

    In the brain, neurons use tightly controlled chemical and electrical signals to communicate with one another in complex networks. Low levels of a protein that facilitates these signals are associated with Alzheimer’s-related memory problems in a mouse model of the disease, according to NIH-supported scientists at the University of California, San Francisco. Restoring levels of the protein, known as Nav1.1, improved learning and memory in the mice and increased lifespan.

    The investigators measured brain-wave activity in mouse models with high levels of beta-amyloid, a pathological hallmark of Alzheimer’s, in the brain. They found that specific abnormalities occurred during periods of reduced gamma-wave oscillations, a type of brain wave involved in regulating learning and memory. They further found that Nav1.1 levels in specialized nerve cells known as parvalbumin cells were decreased in these mice, suggesting an association between reduced Nav1.1 levels and abnormal brain-wave activity. The mice also had impaired memory and decreased lifespan compared with normal mice. However, when Nav1.1 levels were restored, brain-wave activity returned to normal, memory improved, and lifespan increased, despite the continued presence of high levels of beta-amyloid in the brain.

    Further research is needed to see if these findings might extend from mice to humans. But, these observations provide important clues about a potential mechanism involved in network and cognitive dysfunctions. Gamma wave alterations like those addressed in this Alzheimer’s study also occur in other neurological disorders, including epilepsy, autism, and schizophrenia, suggesting that these findings may have implications for these conditions as well.

    Reference: Verret L., et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149: 708-721, April 27, 2012.

  • June 1, 2012

    In two recent studies, NIA-supported investigators identified a surprising new candidate drug treatment for Alzheimer’s disease (AD) and determined a potential mechanism of action for the compound.

    In the first study, researchers demonstrated that bexarotene, a skin cancer drug, reversed AD symptoms in a mouse model of the disease. Researchers at Case Western Reserve University School of Medicine in Cleveland found that within 72 hours of treatment, bexarotene reversed social, cognitive, and olfactory deficits and cleared beta amyloid—a pathological hallmark of AD—from the mice’s brains. Bexarotene treatment was effective in both early and later stages of Alzheimer’s in the mice. The investigators emphasize that while these findings are promising, there is further need for translational research from the animal studies to examine the efficacy of bexarotene in people with AD.

    A second article by researchers at the Indiana University School of Medicine in Indianapolis established a potential mechanism of action for bexarotene. Investigators with the Alzheimer’s Disease Neuroimaging Initiative (ADNI) genotyped 103 ADNI participants and identified a variant of the DHCR 24 gene that was associated with lower brain amyloid levels compared to people without the gene, suggesting that this variant may have a neuroprotective effect. Researchers believe that bexarotene may act through the DHCR 24 pathway, providing further support for continued investigation of bexarotene. Specifically, these findings encourage more studies to evaluate the gene’s possible role in AD pathogenesis.


    Cramer, P. E., et al. ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science. 2012 Mar 23;335(6075):1503-6. Epub 2012 Feb 9.

    Swaminathan S., et al. Amyloid pathway-based candidate gene analysis of [11C]PiB-PET in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, Brain Imaging and Behavior, (2012) 6:1-15. 8.

  • July 25, 2012

    Registration is now open for “Unveiling the NIH Toolbox,” a free scientific conference to be held September 10-11 in Bethesda, Maryland. The meeting will present the NIH Toolbox for Assessment of Neurological and Behavioral Function— a set of brief but comprehensive neurological and behavioral health measurements designed for use particularly in large-scale research studies such as epidemiological studies or clinical trials. Developed by a team of more than 250 scientists from nearly 100 academic institutions, the NIH Toolbox provides a battery of on-line and royalty-free measures of motor, cognitive, sensory and emotional function for study participants aged 3 to 85 years. Developed under the auspices of the NIH Blueprint for Neuroscience Research, a coalition that creates new tools and resources to advance neuroscience research, the highly anticipated NIH Toolbox promotes economies of scale and enhanced efficiency in measurement.

    The meeting will feature lectures, interactive demonstrations, and panel discussions about the development, testing and use of the NIH Toolbox in biomedical research. An optional “Administering the NIH Toolbox” training workshop follows the conference on September 12-15. To register for the conference and/or training workshop, or to learn more about the NIH Toolbox, go to

  • August 8, 2013

    The NIA Grants for Early Medical/Surgical Specialists’ Transition to Aging Research (GEMSSTAR) program provides research grant support to early-stage physicians seeking to bridge their clinical specialty with aging research. This program particularly targets clinician-scientists who have recently completed their residency or fellowship training and are embarking on their first faculty position. In order to receive NIA-funded support for their research project, successful candidates must also secure non-NIH funds to support an individual Professional Development Plan.

    The receipt date for RFA-AG-14-010 is October 21, 2013.

    See detailed information and FAQs »

  • July 12, 2012

    Posiphen, a drug candidate designed and developed by researchers in the NIA’s Intramural Research Program, has been shown in three small, early studies to be well-tolerated and to reduce the generation of amyloid and tau protein—the hallmarks of Alzheimer’s disease—in older people at risk for developing the disorder. The series of dosing, tolerability, and “proof of mechanism” studies was conducted by an international group of investigators testing a pill form of the drug Posiphen during trials of seven to ten days in healthy volunteers and those with mild cognitive impairment (MCI), a condition that often progresses to Alzheimer’s. The report of the research appeared online July 11, 2012 in the Journal of Neurology, Neurosurgery & Psychiatry.

    Posiphen was determined to readily enter the brain and in cerebrospinal fluid tests, scientists found that the drug lowered levels of amyloid, tau, and inflammation—all key targets in the effort to find therapies for Alzheimer’s. Researchers believe the drug may work by inhibiting the production of neurotoxic products that derive from amyloid precursor protein, or APP, and result in the accumulation of abnormal clumps of amyloid. While the finding is preliminary, it does provide key data to move the drug forward for further human testing.

    Reference: Maccecchini, M., et al. Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-b peptide and s levels: target engagement, tolerability and pharmacokinetics in humans. Journal of Neurology, Neurosurgery & Psychiatry. Doi: 10.1136/jnnp-2012-302589.

  • June 29, 2012

    The creation of the first iteration of the Common Alzheimer Disease Research Ontology (CADRO) is a collaborative effort between the National Institute on Aging (NIA) and the Alzheimer’s Association (AA). The project began in May 2010 for the purpose of conducting a comparative analysis of the NIA and AA Alzheimer’s disease (AD) research portfolios. See International Alzheimer's Disease Research Portfolio.

    The purpose of this effort is to inform the development of a comparative analysis of research portfolios among multiple funders of AD research, inform strategic planning and priority-setting, and support coordination by federal and non-federal agencies supporting AD research in the United States and internationally.

    The ultimate goal of this project is to support communication and facilitate in the sharing of priorities among federal and non-federal agencies that support AD research.

    For more information see CADRO.

  • June 25, 2012

    Investigators have identified interventions that extend lifespan in model systems. For example, caloric restriction (CR) – a reduction in caloric intake while maintaining adequate nutrition – has been shown to increase insulin sensitivity, improve health, and extend lifespan in several organisms.  Although scientists do not fully understand the mechanisms through which CR may work, it is generally believed that it functions at least in part through inhibition of the protein complex mTORC1. Another intervention, the immunosuppressive drug rapamycin, extends the lifespans of yeast, flies, and mice, also by inhibiting mTORC1. However, unlike CR, long-term use of rapamycin causes insulin resistance in rodents; in humans, that could lead to diabetes and decreased lifespan.

    NIH-supported investigators recently found that rapamycin disrupts a second protein complex, mTORC2, in mice, and that mTORC2 is required for efficient equilibrium between glucose production and consumption. When scientists decoupled protein complexes mTORC1 and mTORC2 in mice, they found that decreasing mTORC1 signaling alone extended lifespan without changes in glucose tolerance or insulin sensitivity. However, reduction in mTORC2 activity was associated with impaired insulin sensitivity in the liver and no increase in life span.  

    These findings suggest  that rapamycin confers longevity through inhibition of mTORC1 and negatively effects glucose control through inhibition of mTORC2.The investigators note that a compound that would inhibit just mTORC1 might provide many of the same benefits of rapamycin on health and longevity, without the side effects that currently limit rapamycin’s utility.

    Reference: Lamming DW, Le Y, Katajisto P, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335: 1638-1643, 2012. PubMed:

  • July 10, 2012

    Taking the Next Step:   Grants Technical Assistance Workshop is an interactive forum for pre- and post-doctoral students and recent recipients of Ph.D., M.D., or related doctoral degrees with the National Institute on Aging, the world's largest funding source for research on aging and geriatrics. During this intensive 1.5 day workshop attendees will gain an understanding of the NIH grants process from application to award, and NIA staff will discuss research priorities and opportunities in the basic biology of aging, neuroscience, behavioral and social research and clinical geriatrics and gerontology. Attendees will have the opportunity to meet in small groups with NIA staff representative of their field of interest. A session focused on research and funding opportunities in health disparities and aging will highlight this GSA pre-conference workshop.

    Applications are due July 20, 2012.

    The deadline for applications has been extended until August 10th.

    See more information and application.