Research and Funding

Approved Concepts

These concepts were approved at the National Advisory Council on Aging (NACA) meeting on January 18, 2017. We have posted the approved concepts here to give interested researchers maximal lead time to plan projects. Please note that not all concepts will necessarily end up converting to an FOA.

Characteristics, Causes, Contexts, and Consequences of Elder Mistreatment

Mistreatment of the elderly is a widespread and complex problem. It affects not only the victim of abuse, but also the families of both victims and perpetrators, and society as a whole. An analysis of the National Social Life, Health and Aging Project, a nationally-representative survey, revealed that approximately 13 percent of adults aged 57 to 85 experienced verbal, financial, or physical mistreatment over a one-year period. Even more troubling is that due to measurement issues and underreporting, this high percentage of self-reported cases likely represents only a subset of all victims. Facing the same obstacles as the child abuse and intimate partner violence (IPV) fields, barriers to disclosure, detection, and classification hinder advances in identifying indicators, risk factors, and intervention design. Rapidly deployable approaches are needed to improve screening, and bioinformatic approaches are needed to distinguish different types of mistreatment from accidental injury or illness and to identify sine qua non or pathognomonic symptoms and signs. Development of a conceptual framework with objective measures is needed to identify risk and protective factors for different types of elder mistreatment and to better assess and understand their cumulative risk or impact.

In October 2015, the NIH convened experts in child abuse, IPV, emergency medicine and elder mistreatment for the NIH workshop: "Multiple Approaches to Understanding and Preventing Elder Abuse and Mistreatment,” to identify key knowledge gaps and barriers to progress, to share insights, and to consider the potential for the field of elder mistreatment to build on advances and experiences in these research areas. Discussion led to the recommendation to pursue research with use of tested and successful approaches from the fields of child abuse and IPV. This initiative addresses two overarching recommendations from this meeting.

The proposed RFA will solicit research in two high-priority areas: (1) development of new and innovative instruments, tools, and analytic strategies and approaches for detecting and assessing outcomes of elder mistreatment, and (2) identification of early risk factors and protective factors that represent putative intervention targets. Applicants will be encouraged to pursue research that builds on principles and adapts successful approaches from the fields of child abuse and IPV. As the aging population is rapidly growing, so is the number of individuals at risk for mistreatment. If this initiative is successful, it will help develop the evidence base needed to support the design of individual-, family-, and community-level interventions for prevention and to promote recovery and resilience in victims and their families and those who inflicted harm and to prevent revictimization.

Scientific/Research Contact

Melissa Gerald, Ph.D.
Division of Behavioral and Social Research
National Institute on Aging (NIA)
Telephone: 301-402-4156
Email: melissa.gerald@nih.gov

Competitive Renewal of the AMP-AD Target Discovery and Preclinical Validation Project

The Accelerating Medicines Partnership (AMP) is a bold new venture among the National Institutes of Health (NIH), 10 biopharmaceutical companies, and several nonprofit organizations to transform the current model for developing new diagnostics and treatments by jointly identifying and validating promising biological targets of disease. This precompetitive collaboration harnesses collective capabilities, scale, and resources across multiple sectors to improve therapeutic development efforts for complex, heterogeneous diseases. AMP's goal is to understand such diseases more fully through research to identify and validate novel, clinically relevant therapeutic targets. As a result, it is expected to accelerate the process of bringing new medicines to patients. AMP is an umbrella partnership with initial programs in three disease areas:

This multi-sector partnership is managed by the Foundation for the NIH (FNIH). NIH and industry partners are sharing expertise and resources—more than $230 million of combined funding support and in-kind contributions over 5 years—in an integrated governance structure that enables the best-informed scientific contributions from all participants. A critical component of the partnership is making AMP data publicly accessible for use by the broad research community.

The Target Discovery and Preclinical Validation Project is a component of the Accelerating Medicines Partnership for AD (AMP-AD). Its central goal is to shorten the time between the discovery of potential drug targets and the development of new drugs for Alzheimer’s disease treatment and prevention, by integrating the analyses of large-scale molecular data from human brain samples with network modeling approaches and experimental validation. The project is a consortium of six multi-institutional, multidisciplinary cooperative agreements and research grants. The grant awardees are applying cutting-edge systems and network biology approaches to integrate multidimensional human “omics” data (genomic, proteomic, metabolomic) from more than 2,000 human brain and blood samples from individuals at all stages of the disease with clinical and pathological data to:

i) discover novel therapeutic targets for Alzheimer’s disease;
ii) gain a systems-level understanding of the gene, protein, and metabolic networks within which these novel targets operate; and
iii) evaluate their drugability in multiple model organisms

In the first iteration of the AMP-AD Target Discovery and Preclinical Validation Project, the Consortium achieved several key milestones starting from the development of a centralized repository for housing high-dimensional human and animal model ‘omics’ data and analytical results (the AMP-AD Knowledge Portal) and making the data and analytical results broadly available, to developing the first set of network models for AD largely based on RNAseq data, nominating the first set of novel therapeutic targets and initiating their preclinical validation in an array of cell-based and animal models. In addition, the participating teams produced a series of publications ranging from data descriptor manuscripts to manuscripts describing new methodology and new disease insights.

As the Project embarks on its fourth year, several limitations and opportunities are becoming apparent. On the limitations end we are realizing that the data generated by the research teams are so rich and complex that only a fraction of it can be utilized in the predictive modeling during the course of the five-year awards and with the available funding resources. In addition, given that one of the pioneering efforts in the Consortium is to develop a data-driven approach for prioritization of novel targets, there is limited bandwidth for the number of targets that can be followed up and insufficient time for full preclinical validation. Lastly, the AMP-AD data and analytical results cannot be easily mined and used by biologists and clinicians because the development of web-based data visualization tools and interfaces to enable biologists to query and interact with the data are not supported by the current resources (with the exception of small supplemental funding to pilot the development of a prototype for one web-based tool).

Several opportunities have presented themselves as well. The initial, as well as supplemental, funding has enabled the generation of very rich and varied human omic datasets (including WGS on ~2000 AMP-AD brain samples) that lend themselves to a multitude of modeling approaches for target and biomarker discovery. A variety of cell-based and animal models are being characterized relative to network models generated from human data for their use in preclinical validation; a large number (~80) of novel candidate targets have been discovered, many of which promise to be tractable for drug discovery and drug development; a series of interlinked pilot projects focused on biomarker discovery has been launched in year 4 of the awards. Lastly and most importantly, the Consortium is a successful proof of concept that an open-science, large-scale team approach to basic and translational research is a viable and more productive alternative to the current research model.

Scientific/Research Contact

Suzana Petanceska
Division of Neuroscience
National Institute on Aging (NIA)
Telephone: (301) 496-9350
Email: sp440u@nih.gov

Coordinating Center for the Claude D. Pepper Older Americans Independence Centers (OAICs)

The Claude D. Pepper Older Americans Independence Center (OAIC) program supports centers of research excellence and research training leading to improved or maintained functional independence in older age. The OAIC Coordinating Center facilitates interactions among OAICs and serves as a conduit for translating OAIC objectives and findings. Functions of the OAIC include:

  • Sponsoring an annual OAIC Investigators Meeting
  • Developing and maintaining a website for scientific exchange among OAIC investigators, the aging research community, and the public
  • Sharing research resources such as databases of measurement tools and recruitment techniques with other NIA and NIH programs and the broader scientific community
  • Providing logistical and educational support for OAIC investigators including trainees
  • Fostering communication, cooperative arrangements, and collaborative projects among multiple OAIC sites and between OAICs and other NIH- or non-NIH-supported research programs

The OAIC Coordinating Center was established in 2005 through an administrative supplement mechanism to an existing OAIC site. In 2007, the Coordinating Center was competed through an RFA using the P30 mechanism. The RFA specified that the Coordinating Center could be funded as either a core within an existing OAIC or as a stand-alone center. The subsequent, and most recent, re-competition of the Coordinating Center took place by RFA in 2012 using similar provisions.

The NIH Office of Extramural Programs is now requiring that coordinating centers for P30 and other centers programs must be funded through a specific award using a mechanism appropriate to a coordinating center’s functions. Moreover, the current OAIC Coordinating Center award will end in 2018, so an initiative is needed in the current planning cycle for its continuation. In addition, since the Coordinating Center’s inception, the OAICs have evolved into a more active and inter-connected research network. Development of the Coordinating Center’s activities is vital to keep pace with the needs of such a network.

Scientific/Research Contact

Basil Eldadah, M.D., Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging (NIA)
Telephone: (301) 496-6761
Email: eldadahb@mail.nih.gov

Development and Commercial Availability of Cell-Based Tests for Age-Related Changes in Resiliencies to Physical Stressors

Declines in resilience, defined as a dynamic property which enables an organism or individual to resist or recover from the effects of a physiologic or pathologic stressor (i.e., physical in nature) can contribute to a variety of adverse health and functional outcomes as we age. Examples of specific resiliencies include maintenance of cardiovascular function after major surgery, successful fracture union and recovery of hematopoietic function after cancer chemotherapy. Unfortunately, our current understanding of age-related changes in resiliencies to physical stressors is quite limited and interventions to promote or enhance resiliencies are not available. This important research gap prompted the NIA to issue three FY2017 initiatives on the resilience concept. These initiatives are focused on different aspects of the resilience concept:

  1. RFA-AG-17-014 focuses on characterization of resiliencies in humans and underlying mechanisms;
  2. RFA-AG-17-040 focuses on mechanisms underlying global resilience in mice; and
  3. RFA-AG-17-061 focuses on the molecular characterization of individuals who remain free of dementia despite being at high risk for Alzheimer’s disease.

Regardless of one’s perspective on the concept of resilience, we currently lack standardized research tools to probe resiliencies at the cellular level. Critical features of such in vitro tests involve an element of “challenge” or perturbation, assessment of response in a short time scale/real-time, and over a robust range (graded tests). The development and commercial availability of standardized tests of specific resiliencies (e.g., patient-specific tests, in vitro stimulation tests using primary cell cultures or co-culture systems), especially focusing on cellular processes or pathways associated with aging such as DNA damage and repair, cell senescence or inflammation, could lead to a more in-depth understanding of different degrees of resiliency (phenotypic features) and underlying mechanisms. The commercial availability of such assays could:

  • Reveal aging mechanisms underlying decrements, as well as factors contributing to the maintenance of resilient phenotypes.
  • Complement and inform studies in pre-clinical models and vice versa (e.g., help to identify potential common mechanisms underlying resiliencies).
  • Accelerate research progress on the characterization of cellular mechanisms underlying physiologic responses and the identification of novel therapeutic targets and interventions to enhance resiliencies as we age.
  • Be used as clinical diagnostics (i.e., patient-specific assays) and improve clinical management of patients.

Importantly the availability of such standardized research tools would also facilitate the comparison of findings across different studies of resilience. The proposed set of FY2018 FOAs on the development and commercialization of cell-based assays of resiliencies are timed to work in tandem and in conjunction with the projects supported by the FY2017 initiatives so that important research tools will be available to enhance their research progress.

Scientific/Research Contact

Chhanda Dutta, Ph.D.
Chief, Clinical Gerontology Branch
Division of Geriatrics and Clinical Gerontology
National Institute on Aging (NIA)
Telephone: (301) 435-3048
Email:DuttaC@nia.nih.gov

Effects of Aging on Hematopoiesis

Hematopoiesis is often considered as a lifelong process in which myeloid and lymphoid cells are continually generated throughout life. However, it is now evident that there is a decline in T and B cell development with age, whereas myelopoiesis remains relatively stable. This is thought to contribute to the impairment of immune function observed in the elderly which is associated with an increased susceptibility to various infectious diseases and a reduced efficacy of vaccination regimens. It is thought that age-related changes in the microenvironment of the bone marrow such as an accumulation of adipocytes and plasma cells may contribute to the decreased capacity of the hematopoietic microenvironment to support lymphopoiesis. The identification of various factors regulating the differentiation of hematopoietic stem cells with aging have significant implications for our understanding of age-associated immune dysfunction and may lead to the development of new therapeutic approaches to rejuvenate the aged immune system. There is a need for a greater understanding of the basic biology that regulates hematopoiesis in older individuals. The gaps in our knowledge and technology of the pathogenesis of non-malignant hematologic disease in older adults was addressed at a workshop held in 2016 as part of a continuing program on hematology research at NIDDK: the SHINE program (Stimulating Hematology Investigators New Endeavors: PAS-16-033).

Scientific/Research Contact

Nalini Raghavachari, Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging (NIA)
Telephone: (301) 435-3048
Email: nraghavachari@mail.nih.gov

HIV and Aging

The number of older individuals living with HIV is rising. In 2005, 29 percent of Americans infected with HIV were age 50 years or older. By 2012, this proportion had risen to 42 percent. By 2020, it is projected that over half of HIV-infected Americans will be 50 years or older. These trends are mirrored globally. The rise in HIV infection among older individuals is due primarily to the successes of modern antiretroviral therapy, which has allowed individuals infected at a younger age to survive well into older age. A smaller but growing fraction of the rising prevalence of HIV in older adults is attributed to new infections in later life.

In contrast to the pre-modern era of HIV treatment, where AIDS-related opportunistic infections and cancers were common, the most frequent morbidities and causes of death currently in treated HIV infection are similar to those seen in older non-infected adults. These so-called HIV-Associated Non-AIDS (HANA) conditions include cardiovascular disease, lung disease, infection-related and non-infection-related cancers, HIV-associated neurocognitive disorders (HAND), neuropsychiatric disorders, osteopenia/osteoporosis, liver cirrhosis, and renal disease. In addition, individuals living with HIV infection may exhibit many of the clinical and socio-behavioral characteristics commonly observed in aging, such as multiple comorbidities, polypharmacy, declining physical and cognitive function, alterations in body composition, social isolation, and increasing caregiver burden. People living with HIV also exhibit molecular changes associated with aging such as epigenetic alterations, mitochondrial impairment, and telomere shortening. Thus, accumulating evidence suggests that HIV and/or its treatment may lead, at least in part, to an accelerated aging phenotype.

In 2015, the NIH Office of AIDS Research (OAR) released NOT-OD-15-137 outlining scientific priorities that would be the basis for HIV-related research funding. These priorities are:

  1. research to reduce the incidence of HIV/AIDS, including the development of safe and effective HIV/AIDS vaccines;
  2. development of the next generation of HIV therapies with improved safety and ease of use;
  3. research towards a cure for HIV/AIDS; and
  4. HIV-associated comorbidities and co-infections.”

The Notice also identified support for “[b]asic research, health disparities, and training that cross-cut these priorities.” These priorities suggest numerous opportunities for studying HIV and aging-related research questions.

This initiative will focus on the intersection of HIV and aging by addressing two overarching objectives:

  1. to improve understanding biological, clinical, and socio-behavioral aspects of aging through the lens of HIV infection and its treatment; and conversely,
  2. to improve approaches for testing, prevention, and treatment of HIV/AIDS, and management of HIV-related related comorbidities, co-infections, and complications in different populations and cultural settings by applying our current understanding of aging science.

Scientific/Research Contact

Basil Eldadah, M.D., Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging (NIA)
Telephone: (301) 496-6761
Email: eldadahb@mail.nih.gov

Novel Mechanisms of Non-autonomous Signaling in Aging and Longevity

The key question to be answered under this RFA is “How is cell-autonomous aging communicated to other cells?” In the past few decades, most of the studies on the molecular mechanisms of aging have focused on the events within cells (cell-autonomous aging). These studies have led to a quite comprehensive understanding of the cell-autonomous mechanisms of aging, including changes in many genes, pathways, biomolecules, and organelles involved in the aging process. A dominant hypothesis, supported by observations obtained in the past several decades, has been that the underlying cause of aging is the cell-autonomous, time-dependent accumulation of stochastic damage to biomolecules, organelles, and cells. However, it has become apparent in recent years that cell-autonomous mechanisms alone are inadequate to explain aging at a tissue or organismal level. In multicellular organisms, it would be hard to imagine that cell-autonomous changes would limit their impact only within the border of a cell without causing cell non-autonomous consequences that affect aging at a tissue or organismal level. In fact, some compelling evidence in recent years, such as parabiosis, serum transfer, cell ablation, and molecular mechanistic studies, suggests that cell non-autonomous mechanisms also play important roles in driving degenerative changes of aging that arise as the consequence of cell-autonomous aging. Although the damages and changes initially occur in specific cells and tissues, it seems that these initial changes need to be communicated to other cells, tissues, or organs and thereby impact lifespan and healthspan of the organism. For most of the non-autonomous players, we don’t know what they are, how they are released from cells, how they are transported and communicated to other cells, and how they elicit aging-processes upon reaching their target cells. This proposed RFA aims to stimulate research on a better understanding of the cell non-autonomous signaling in aging.

Scientific/Research Contacts

Max Guo, Ph.D.
Division of Aging Biology
National Institute on Aging (NIA)
Telephone: (301) 402-7747
Email: max.guo@nih.gov

Jose Velazquez, Ph.D.
Division of Aging Biology
National Institute on Aging (NIA)
Telephone: (301) 496-6402
Email: jvelazqu@mail.nih.gov

Socioeconomic Disparities in Health at Older Ages

It has long been established that better-educated and higher-income people live longer, on average, than less educated and lower income people. But in recent decades, there have emerged new, surprising and largely unexplained trends: the gaps in life expectancy at older ages by income, education, and geographic region have been widening in the United States. In June 2016, BSR sponsored an expert meeting of the National Academy of Sciences Committee on Population entitled “Health Disparities Across the Life Cycle.” Workshop participants discussed the recent research findings pointing to widening health disparities in the US and what the implications might be for NIA’s research agenda. (See workshop summary) Given the momentum generated by this workshop, and by the recent availability of datasets with life history information and with linkages to geographic contextual data, the time is ripe for an NIA initiative that will contribute to the literature on this topic, moving beyond description to the identification of mechanisms and modifiable risk factors.

Scientific/Research Contact

Georgeanne Patmios, MPH
Division of Behavioral and Social Research
National Institute on Aging (NIA)
Telephone: (301) 496-3138
Email: gp29p@nih.gov