Approved Concepts

Advance Aging Research through Centers for Medicare & Medicaid Services (CMS) Data Linkage

NIA and NIH promote data sharing and accessibility as key drivers of research discovery. In 2021, NIA established the Data Linkage Program to link NIA-funded study data with Centers for Medicare and Medicaid Services (CMS) data. The LINKAGE program has successfully linked CMS data to more than 30 studies that focus on caregiving, disability, mortality, dementia diagnosis and more. More recently, it has refined its infrastructure and expanded capacity to take on additional studies requiring data linkage.

This concept aims to support linking of NIA-funded study data with CMS data. This effort will reduce the administrative, financial, and information technology security barriers that may inhibit studies from data sharing. This concept proposes solicit applications from NIA-funded investigators with active awards seeking to link their study data to CMS data, with the goal of advancing our understanding of health care delivery and health outcomes in older adults, including people who are affected by or at risk for Alzheimer’s disease and related dementias.

Scientific/Research Contacts:

Irim Azam. M.P.H.
Division of Behavioral and Social Research

Nina Silverberg, Ph.D.
Division of Neuroscience

Marcel Salive, M.D., M.P.H.
Division of Geriatrics and Clinical Gerontology

Inquiries: Email linkage@nih.gov

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Advancing Diversity in Aging Research Through Undergraduate Education (ADAR) Program Coordinating Center

In a little over a decade, the Advancing Diversity in Aging Research through Undergraduate Education (ADAR) program has matured to provide intensive aging research experiences that help undergraduate students transition into strong, research-focused advanced degree programs or competitive private sector research careers in aging-related disciplines. There are currently 36 unique ADAR programs in 14 states and the District of Columbia. ADAR has been extremely successful in building new pathways for investigators in aging and Alzheimer’s and related dementias. It has reached nearly 700 undergraduate students, large percentages of whom are women and students from groups underrepresented in biomedical and behavioral research. Additionally, more than half of ADAR participants were accepted to graduate school with 83% in aging-related graduate programs.

Given the maturity and expansion of the ADAR program, there is a need for more centralized and coordinated efforts, infrastructure, and resources to increase efficiency and streamline processes across multiple high-quality research projects. This concept proposes establishing a coordinating center for the ADAR program, to:

• Facilitate collaboration, recruitment and organization between ADAR, participants, and NIA
• Create and maintain an ADAR coordinating center website
• Support virtual and in-person learning activities, networking opportunities, and career resources
• Collect, analyze and evaluate relevant data, including from previous ADAR cohorts to document impact, trends, and trajectories
• Plan, arrange, and facilitate the program-wide ADAR Summit and other annual meetings

Scientific/Research Contacts:

Maria Carranza, Ph.D.
Office of Strategic Extramural Programs
Email Maria Carranza

Delany Torres, Ph.D.
Division of Behavioral and Social Research
Email Delany Torres

Shreaya Chakroborty, Ph.D.
Division of Neuroscience
Email Shreaya Chakroborty

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Aging Mammalian Tissues In Vitro

Human-relevant models are essential to fully understand the biology of human aging in the context of the general principles of aging derived from research on animals. Recent scientific advances in technologies for culturing in vitro human tissues and induced pluripotent stem cells (iPSCs) are expanding the types of complex 3-dimensional (3D) in vitro models available to investigators. In vitro models including microphysiological systems are amenable to genetic manipulation, longitudinal phenotyping, and mechanistic studies. A successful in vitro model of aging is one that faithfully and reproducibly recapitulates aging processes and phenotypes, can be validated and broadly adopted. We need to establish what questions are best addressed using human in vitro systems and to develop tools and technologies for their implementation as complementary models in addition to research in animals and clinical studies.

This concept will support the development of mammalian 3D in vitro tissue systems to model aging to gain insight into the biology of aging and as new tools for screening and testing geroprotectant interventions.

Scientific/Research Contact:

Tiziana Cogliati, Ph.D.
Division of Aging Biology
Email Tiziana Cogliati

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Artificial Intelligence and Technology Collaboratory Renewal

Artificial intelligence (AI) and other emerging technologies hold great promise for addressing pressing issues in aging and dementia research. These approaches have the potential to improve the health and well-being of older adults, including individuals living with dementia and their caregivers. NIA’s Artificial Intelligence and Technology Collaboratory (AITC) program supports innovative cross-disciplinary collaborative teams performing cutting-edge demonstration projects using AI and tech approaches.

This concept aims to continue and expand the AITC program to help meet the increasing demand for AITC resources and equitably address scientific priorities across NIA. Each AITC must promote a sustainable research and infrastructure development program in one or more cross-cutting thematic areas in aging and dementia, which may include:

• Resources to promote AI and machine learning (ML) ready datasets
• Design and modification of technology by incorporating AI applications into human factors problems/design associated with aging and Alzheimer’s and related dementias
• Resources to promote integration of experimental and AI/ML approaches to better understand basic processes in the aging brain and Alzheimer’s and related dementias
• Computational and informatics tools applied to the study of aging mechanisms
• AI, ML, or health monitoring technologies in aging research
• AI-driven systems biology and technological innovations for aging research
• Imaging and image analysis
• AI-driven clinical decision support tools to enable personalized care for older adults with multiple chronic conditions

Scientific/Research Contacts:

Rebecca Krupenevich, Ph.D.
Division of Behavioral and Social Research

Amanda DiBattista, Ph.D.
Division of Neuroscience

Marcel Salive, M.D., M.P.H.
Division of Geriatrics and Clinical Gerontology

Leonid Tsap, Ph.D.
Division of Aging Biology

Inquiries: NIAAITC@nih.gov

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Bats and Healthy Aging

Bats are emerging as an important animal model for the science of aging. Recent research has uncovered several critical advantages of bats including biological, behavioral, and social similarities to humans. They also feature unique characteristics related to healthy aging including exceptional longevity, high immune system tolerance for viral infections, and reduced inflammatory response to cytokines and oxidative stress. Bats also have a natural resistance to age-related conditions like osteoporosis and hearing loss.

This concept will focus on the characterization and validation of wild and captive bat populations as models for aging research. It aims to explore potential biological, physiological, sensory, behavioral, and social aging processes that contribute to longevity and healthspan in bats and to develop novel interventions for age-related disorders. It will also include a multidisciplinary review panel to critically evaluate the success of bats as models of aging.

Scientific/Research Contact:

Manuel Moro, D.V.M., Ph.D.
Division of Aging Biology
Email Manuel Moro

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Caring for Complex Older Adults Through Electronic Health Record Dashboards (COATED)

The development of multiple chronic conditions (multimorbidity) and complex medical conditions is common with aging and is often linked to higher health care costs and poorer health outcomes. Electronic health record (EHR)-based interventions have demonstrated success in improving care delivery and uptake of health behaviors among older adults. EHR-based dashboards can provide clinical decision-making tools to optimize whole-person care of older adults by targeting healthier behaviors and reducing inefficiencies and fragmentation in care delivery, leading to improved outcomes.

This concept will support collaborations between researchers, health systems, clinicians, and multiple EHR vendors to design, build, test, and evaluate dashboards to improve the care of older adults with complex medical conditions in primary care. This initiative will conduct research and develop infrastructure including identifying existing interventions ready for scale and implementation; developing public-private partnerships and engaging key audiences; adapting or building a data and analytics platform; designing and testing dashboards for complex care management and/or guidelines for concordant care; fostering communication between patients and clinicians; and disseminating information and tools.

Scientific/Research Contact:

Marcel Salive, M.D., M.P.H.
Division of Geriatrics and Clinical Gerontology
Email Marcel Salive

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Data Coordinating Center for the Aging and Alzheimer’s Disease Mouse Brain Atlas (AD-MBA)

The progression of Alzheimer’s disease often follows a predictable temporal and spatial pattern where specific brain regions are affected at different stages of the disease. However, it is unknown why the disease affects certain regions of the brain or why specific cell subpopulations within these brain regions are selectively vulnerable. To better understand the mechanisms and impact of Alzheimer’s progression in different brain regions and cell types, NIA supports multiple projects using mouse models to generate comprehensive atlases of brain cell types and circuits that are altered during aging and dementia. Currently, there is no dedicated support for a centralized data sharing, integration, and dissemination infrastructure, and thus these valuable datasets remain siloed.

This concept seeks to address these critical needs by unifying these multiscale datasets and creating a central, unified research resource: The Aging and AD Mouse Brain Atlas (AD-MBA). Creation of the AD-MBA will include establishment of a data coordinating center to facilitate collaborations across groups, perform intensive analysis of multiscale datasets, and manage their dissemination. A successful coordinating center will:

• Integrate and harmonize existing multi-modal datasets from a subset of NIA-supported studies
• Develop and incorporate tools for multi-scale modeling of multi-omics and connectomics datasets
• Create an accessible web-based platform to disseminate integrated data
• Capitalize on existing resources and infrastructure, including the AD Knowledge Portal, and enable future alignment with other NIH programs, such as MODEL-AD and the BRAIN Initiative

Scientific/Research Contacts:

Erin Gray, Ph.D.
Division of Neuroscience
Email Erin Gray

Nandini Arunkumar, Ph.D.
Division of Neuroscience
Email Nandini Arunkumar

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Dementia Care and Caregiver Support Intervention Research — Stage I Only

Research on dementia care and caregiving is abundant, and literature reviews highlight the need for fully-powered efficacy and effectiveness studies where the hypothesized essential components and principles of the interventions are well-specified and fidelity in intervention delivery is maximized. Following the NIH Stage Model of intervention development, Stage I intervention research plays a key role in preparing for these fully-powered later stage trials, which typically include the following activities: developing or adapting intervention materials (including training materials); demonstrating that the intervention can be delivered with fidelity; and establishing that the intervention is relevant, acceptable, and feasible for participants.

This concept is distinct from a companion concept supporting intervention research at later stages of the NIH Stage Model (Stages II-V). Having distinct — but companion — concepts allows for a Stage I concept that lays the foundation for subsequent fully-powered clinical trials that result in effective interventions defined by their principles and can be implemented in a sustainable way where they are needed.

Scientific/Research Contact:

Melissa Riddle, Ph.D.
Division of Behavioral and Social Research
Email Melissa Riddle

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Dementia Care and Caregiver Support Intervention Research — Stages II through V

The research field on dementia care and caregiving has grown tremendously in recent years. Reviews of that research highlight the need for fully-powered efficacy and effectiveness studies where the hypothesized essential components and principles of the interventions are well-specified and fidelity in intervention delivery is maximized. Following the NIH Stage Model of intervention development, this efficacy and effectiveness testing happens in Stages II and III (efficacy), and Stage IV (effectiveness). Once it has been shown that an intervention can be delivered with fidelity in the “real world,” with demonstrated effectiveness, efforts turn toward testing strategies to getting the intervention adopted (Stage V implementation science). For Stages II-IV research, it is expected that, at a minimum, Stage I activities will already have been completed, so that intervention materials and training procedures (where applicable) are developed, and that the intervention has demonstrated relevance, acceptability, and feasibility for the target participants. For Stage V research, it is expected that, at a minimum, successful Stage IV intervention research has been conducted.

This concept is distinct from a companion concept supporting intervention research at Stage I of the NIH Stage Model. To support a robust planning phase before launching a subsequent clinical trial, the concept for Stage II-V is a milestone-driven phased concept, with a planning phase, followed by a clinical trial phase, if planning is successful. The main goals of the clinical trial planning phase are finalizing study procedures and demonstrating acceptability and feasibility of those procedures. These activities are in contrast to Stage I activities, which focus on establishing the acceptability and feasibility of the intervention itself. The ultimate goal of this concept is to encourage research that leads to effective interventions defined by their principles, that can be implemented in a sustainable way where they are needed.

Scientific/Research Contact:

Melissa Riddle, Ph.D.
Division of Behavioral and Social Research
Email Melissa Riddle

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Interdisciplinary Research Network on Housing and Health

Housing is a critical determinant of health which operates through four main pathways: stability, safety and quality, affordability, and neighborhood. Better understanding these pathways and addressing identified gaps in the literature translate to real public health gains. However, progress is stymied because of the siloing of relevant research disciplines. This concept seeks to address the fragmented nature of the housing field by convening researchers across disciplines to advance our understanding of how housing affects health.

Specifically, this concept will support an Interdisciplinary Research Network on Housing and Health that will undertake a series of activities to overcome barriers to advancing this field. Key among them is a series of cross-disciplinary pilot projects that generated by new, interdisciplinary teams. The network will foster these connections by gathering researchers from different disciplines. Network-specific activities will include workshops, webinars, in-person gatherings, systematic activities to identify and prioritize research gaps (e.g., literature reviews), trainings, and data sharing. Combined, these activities can form and support new, interdisciplinary collaborations that will, in turn, address neglected research areas at the intersection of housing and health.

Scientific/Research Contact:

Kriti Jain, M.S.P.H., Ph.D.
Division of Behavioral and Social Research
Email Kriti Jain

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Interdisciplinary Research to Understand the Complex Biology of Resilience to Alzheimer’s and Related Dementias Disease Risk

Development of future effective treatment and prevention strategies for Alzheimer’s and related dementias requires a deeper understanding of the mechanisms leading to cognitive resilience despite the presence of dementia risk factors and biomarkers. NIA-supported studies of rare resilient subjects such as the Colombia-Boston Biomarker Research Study (COLBOS) have offered insights into the role of molecular mechanisms of resilience. In parallel, a growing number of genetically diverse animal models and induced pluripotent stem cells (iPSCs) from high-risk individuals are spurring the discovery of resilience-based mechanisms and potential drug targets.

This concept will build on progress made by the prior iterations of this funding initiative that led to the establishment of the Resilience-AD program. The goal is to continue the development of a robust program that integrates epidemiologic, genomic, and mechanistic research through the use of data-driven approaches to understand the molecular and cellular determinants of resilience to various types of AD/ADRD risk across diverse populations. This highly cross-disciplinary program will lay the foundation for new therapeutic strategies for disease prevention within a precision medicine paradigm. Some examples of research areas of interest include:

• Gene-environment interactions leading to resilient phenotypes across diverse populations
• Preclinical validation of candidate resilience targets across multiple cell-based and animal models
• Cross-species integration to ensure the relevance of insights for human biology
• Identification of cell types, molecular subtypes, and spatial contexts relevant to resilience mechanisms

This highly cross-disciplinary program aims to lay the foundation for new therapeutic strategies for disease prevention within a precision medicine paradigm.

Scientific/Research Contact:

Jennifer Isaacs, Ph.D.
Division of Neuroscience
Email Jennifer Isaacs

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Institutional Research Training Award for AD/ADRD And Aging Research in Low- and Middle-Income Countries (LMICs)

The proportion of the world’s population that is age 60 and older will double from 1 billion in 2019 to over 2 billion in by 2050, with the largest increases in low- and middle-income countries (LMICs). Currently, LMICs lack resources to deal with the health and social challenges of an increasing older population, and approximately 75% of LMICs have little or no data to inform evidence-based strategies for healthy aging. In parallel, more than two-thirds of people living with Alzheimer’s and related dementias worldwide are in LMICs. Global research and cross-country comparisons may assist in improving our understanding of aging and dementia among diverse populations, yet the majority of this research is conducted in high-income countries. Training the next generation of aging and dementia researchers in LMICs is critical for more equitable aging and dementia research. NIA has initiated efforts to build research workforce training capacity in LMICs, but more coordinated training among early education and career levels is needed.

This concept aims to leverage NIA’s investment in research in LMICs and support coordinated training efforts among LMIC graduate and post-doctoral trainees to complement NIA’s ongoing global health efforts. The overarching goal is to build capacity to conduct innovative and collaborative global research that will accelerate the pace of aging and Alzheimer’s and related dementias research in LMICs. Specifically, this concept will:

• Support collaborations between the United States and LMIC institutions to create sustainable and relevant training-related mentored research projects
• Develop and/or strengthen the capacity of the LMIC institution to train a cadre of experts who are likely to contribute to aging science advances in their country
• Establish an institutional program for mentored training in LMICs

Scientific/Research Contacts:

Damali Martin, Ph.D., M.P.H.
Division of Neuroscience
Email Damali Martin

Delany Torres, Ph.D.
Division of Behavioral and Social Research
Email Delany Torres

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National Alzheimer’s Coordinating Center (NACC)

The National Alzheimer’s Coordinating Center is an essential part of NIA-funded infrastructure for Alzheimer’s and related dementias research. NACC actively supports a large relational database of standardized longitudinal clinical data from more than 50,000 participants seen at the 35 Alzheimer’s Disease Research Centers (ADRCs).

This concept aims to support the reorganization, evolution, and growth required to sustain NACC’s new scale, meet critical modernization needs, and deliver on expanded data, collaboration and communication research objectives and coordination activities. It will enable innovations to promote more efficient data sharing and transform how NACC:

• Collects data from ADRCs
• Integrates and harmonizes existing and new data streams
• Ensures data quality
• Makes all ADRC data searchable, accessible, and visualizable

Scientific/Research Contact:
Cerise Elliott, Ph.D.
Division of Neuroscience
Email Cerise Elliott

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National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD)

NCRAD is an essential centralized infrastructure for NIA-funded Alzheimer’s and related dementias research, providing a biorepository that currently supports 74 studies with two million samples from 126,000 individuals. The repository provides samples to more than 200 researchers from these studies and is necessary to multiple NIA infrastructure projects including the National Alzheimer’s Coordinating Center, Alzheimer’s Disease Sequencing Project Functional Genomics Consortium, and Center for Alzheimer’s and Related Dementia.

This concept proposes the continuation of this central biospecimen repository for dementia studies and its facilitation of sample sharing to all qualified investigators, as well as the biomarker assessment laboratory, which advances biomarker research with high quality control and harmonization with other laboratories. This concept will support continued growth for NCRAD, including, but not limited to:

• Comprehensive study-specific biospecimen management that implements best practices and uniform processes
• Implementation of rigorous specimen quality standards to support the broadest range of experiments
• Banking of a wide range of tissues and specimens to support the development of novel biomarkers
• Addressing disparities in dementia research by banking studies that recruit participants from underrepresented populations
• Ensuring capacity to generate high-quality dementia biomarkers
• Facilitate innovation, discovery, rigor and reproducibility through a unique model for sample distribution

Scientific/Research Contact:

Cerise Elliott, Ph.D.
Division of Neuroscience
Email Cerise Elliott

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National Longitudinal Study of Adolescent to Adult Health (Add Health) Wave VII Renewal

The National Longitudinal Study of Adolescent to Adult Health (Add Health) is a nationally representative, racially and ethnically diverse U.S. longitudinal study that began when participants were around 12-20 years old and has continued across six waves into participants’ forties. This study provides an opportunity to contribute to understanding the life course determinants of Alzheimer’s and related dementias and inequities therein. Dementia is increasingly recognized as unfolding across the life course, but most studies begin several decades into life, missing an opportunity to capture potentially modifiable social, psychological, and biological processes in childhood and midlife.

This concept proposes a renewal of the study and a seventh wave of data collection when participants are projected to be age 49 on average. The Add Health Wave VII renewal will integrate survey approaches that ensure continued population representation in this longitudinal diverse cohort with multi-domain measures that will enable researchers to examine the modifiable processes shaping inequities in Alzheimer’s and related dementias risk. Goals of this concept include:

• Re-interviewing eligible participants in a mixed-mode survey design that preserves sample population representation and includes measures of midlife factors salient for dementia risk including those that link early life factors with cognitive aging and that shape inequities
• Revisiting respondents for an in-home health visit including venous blood collection
• Assaying blood for biomarkers relevant to Alzheimer’s and related dementias risk
• Conducting a comprehensive assessment of cognitive, physical, and sensory function
• Updating mortality information from administrative data and other sources
• Cleaning, documenting, disseminating, and archiving public and restricted access data

Scientific/Research Contacts:

Amelia Karraker, Ph.D.
Division of Behavioral and Social Research
E-mail Amelia Karraker

Emily Hooker, Ph.D.
Division of Behavioral and Social Research
Email Emily Hooker

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New Institutional Training Programs for Aging Research

Institutional Research Training Grants are a cornerstone of NIA’s training and career development program. These grants provide support to institutions to select predoctoral and/or postdoctoral scholars for training and develop a program of coursework, mentored research experiences, and relevant technical and professional skill development.

To help diversify NIA’s training ecosystem and expand pathways for investigators in aging research, this concept proposes increasing funding for new institutional training programs for aging research. High priority research areas for training will be emphasized and institutions that have not previously held these kinds of awards will be encouraged to apply.

Scientific/Research Contact:

Laura Major, Dr.P.H.
Office of Strategic Extramural Programs
Email Laura Major

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Renewal of Clinician-Scientist Transdisciplinary Aging Research (Clin-STAR) Coordinating Center

Emerging clinicians who recognize the importance of aging within their discipline may benefit from essential guidance and resources to become competitive in aging research. Such support can facilitate transdisciplinary research approaches that better reflect the real-world needs of complex care for older adults. The Clin-STAR Coordinating Center was established in 2019 to facilitate knowledge exchange on the care of older adults; provide vital mentoring and career development support for emerging clinician-scientists committed to aging research; and foster interdisciplinary networking, collaboration, and pilot research projects. Clin-STAR builds on the success of the NIA Grants for Early Medical and Surgical Specialists’ Transition to Aging Research (GEMSSTAR) award program to encompass clinician-scientists across all clinical disciplines relevant to aging research.

This concept aims to support continuation and expansion of the Clin-STAR Coordinating Center. In addition to continuing current high-value programs, applicants may propose activities including, but not limited to:

• Special pilot funding and faculty exchange programs
• Expanded networking and collaboration tools
• Development of enhanced mentoring infrastructure

Among the key priorities in this renewal concept are increased involvement of allied health clinician-scientists from the breadth of relevant specialties and disciplines in Clin-STAR's leadership, mentoring faculty, and early career recipients; enhanced efforts to promote diversity and equity in all of Clin-STAR's activities; and increased reach of Clin-STAR's offerings to investigators and institutions in limited-resource settings.

Scientific/Research Contact:

Basil Eldadah, M.D., Ph.D.
Division of Geriatrics and Clinical Gerontology
Email Basil Eldadah

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Renewal — Social, Behavioral, and Economic (SBE) COVID Coordinating Center

Policies enacted during the COVID-19 pandemic such as health care availability, coverage, and delivery as well as school closures, eviction moratoriums, and access to remote work, may indirectly influence health and health disparities. There is a need to facilitate research and share results that assess the impact of the recent COVID-19 pandemic policies on population health and health disparities. In particular, understanding how behavioral, social, and economic (SBE) factors are modified by pandemics and pandemic-related policies both in the short- and long-term can provide vital insights. To better understand this impact and inform future policy, the NIH Social, Behavioral, and Economic Research on COVID-19 Consortium was established to advance research on COVID-19 mitigation efforts and economic disruption on health-related outcomes, with close attention to underserved and vulnerable populations.

This concept aims to support renewal of the consortium coordinating center. Continuing the coordinating center will allow for ongoing coordination of consortium research projects and shift the Consortium’s focus to fostering research in the broader community through conferences, workshops, data development, discovery, and sharing as well as a pilot research program that examines the long-term effects of the pandemic and related policies on health. These efforts could support continued research on the long-term ramifications of the pandemic and inform the future pandemic response via the development of a “lessons learned” toolkit. It would also provide an avenue for rapid response for urgent workshop, pilot research, or data needs that NIH encounters in the future.

Scientific/Research Contact:

John Phillips, Ph.D.
Division of Behavioral and Social Research
Email John Phillips

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RNA Metabolism in Aging and Aging-Related Diseases

Recent research supports the pivotal role of RNA in cellular functions, such as protein synthesis and the regulation of gene expression. RNA editing, alternative splicing, and RNA modification have all been implicated in the regulation of aging and longevity, yet their underlying mechanisms remain largely unknown. Recent technological advances, such as DNA and RNA sequencing, single cell and spatial omics technologies, offer new opportunities to investigate the intricate roles of RNA metabolism.

This concept aims to support the identification and characterization of RNA editing, alternative splicing, and RNA modification that are associated with the aging process and aging-related diseases (excluding Alzheimer’s and related dementias). Collaborative efforts leveraging cutting-edge technologies are encouraged to address critical mechanistic questions related to aging. Areas of interest include, but are not limited to examining how changes in RNA metabolism may:

• Play causal roles in the aging process
• Be related to aging hallmarks
• Contribute to cellular and physiological dysfunction in aging at the molecular level
• Serve as potential biomarkers or therapeutic targets for aging-related diseases
• Contribute to heterogeneity in aging and aging diseases
• Play roles in the mitochondria and other organelles in aging process or aging-related diseases

Scientific/Research Contacts:

Max Guo, Ph.D.
Division of Aging Biology
Email Max Guo

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Transition to Aging Research for Predoctoral Students

Launched in 2020, NIA’s Transition to Aging Research Award (F99/K00) aims to help support advanced graduate students to complete their doctoral degrees in biomedical research, and transition to postdoctoral training in aging research. However, slight adjustments to the award are needed to help increase the success of the program and reduce barriers to prospective applicants. For example, U.S. biomedical graduate programs are concentrated in the same high cost-of-living areas that receive the majority of overall NIH funding. Therefore, strong financial support for predoctoral students is essential to prevent student financial stress and attrition. In addition, adjusting the timing and number of the award receipt dates to better align with doctoral graduation will allow more applicants to prepare competitive submissions. Finally, expanding the number of supported applications will help ensure the program can keep pace with demand for the award and the increasing number of meritorious applications received.

To enhance the Transition to Aging Research Award program, this concept aims to expand to two due dates per year and better align the award timeline with doctoral graduation timelines; increase the overall number of supported applications each year; and further consider ways to best support this population.

Scientific/Research Contact:

Jamie Lahvic, Ph.D.
Office of Strategic Extramural Programs
Email Jamie Lahvic

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Translational Center for Accelerating the Use of Digital Technologies in Alzheimer’s Disease and Related Dementias Research

Recent advances in digital health technologies (DHT), such as wearable devices and sensors, combined with improved computational power and analytic approaches, provide an opportunity for a new approach for risk assessment, early detection, and monitoring of Alzheimer’s and related dementias. Remote collection of data may also improve recruitment of diverse participants and reduce participant burden. While NIA has supported the collection of DHT data across many brain aging and dementia programs, the lack of an open-source ecosystem for secure data storage, harmonization, and integration with other patient level data remains a major obstacle for the wider use of DHT data in translational and clinical research.

This concept proposes a new funding initiative that will develop the data infrastructure for secure hosting, aggregation, and dissemination of DHT data and the methodology to accelerate their use in dementia research. The major research activities would include:

• Establishing a FAIR data repository, designed to provide secure storage and access to existing and newly generated DHT data and interoperability with NIA’s data repositories for genomic and phenotypic data for Alzheimer’s and related dementias.
• Enabling pooling of digital data across different studies and develop analytical methods for integration of DHT data with other clinical data (e.g., imaging and fluid biomarkers) and high-dimensional molecular data (e.g., genomic, proteomic, metabolomic).
• Developing technical standards, implementing best practices, and providing expert knowledge for the use/deployment of DHT to enhance research rigor and data interoperability and comparability across Alzheimer’s and related dementias clinical research that can meet regulatory expectations.

Scientific/Research Contacts:

Nadezda Radoja, Ph.D.
Division of Neuroscience
Email Nadezda Radoja

Yuan Luo, Ph.D.
Division of Neuroscience
Email Yuan Luo

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Digital Technologies as Tools to Screen and Monitor Alzheimer’s Disease and Related Dementias

While some new Alzheimer’s disease and related dementias drugs have become available, there are still significant gaps in Alzheimer’s screening, early detection, clinical trial enrollment, monitoring, and treatment evaluation. There is growing interest in the development, standardization, and validation of cost-effective digital technologies, including software and mobile device applications, to address this need. Analysis of gait, speech, eye movement, hearing, or other factors associated with cognitive impairment using digital tools may support earlier disease detection and long-term monitoring of disease progress. However, to be universally accepted, these tools need to be standardized and validated in diverse populations.

This concept aims to stimulate the participation of small businesses in the Food and Drug Administration’s (FDA) Medical Device Development Tools program to develop and demonstrate the utility of digital technologies for Alzheimer’s disease and related dementias screening and monitoring as qualified tools to assess medical devices subject to regulation by the FDA.

Scientific/Research Contact:

Rajesh Kumar, Ph.D.
Office of Strategic Extramural Programs
Email Rajesh Kumar

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Leveraging Multimodal and Generative Artificial Intelligence to Advance the Application of Social Robotics in Caregiving

Caregiving for people living with dementia can be physically and psychologically challenging. Many existing assistive mobile or web-based technologies designed to ease caregiving burden have a limited scope, are too complex, and/or require a high level of digital accessibility or literacy for use. Overall, many current options fail to meaningfully engage people living with dementia and their caregivers. Ongoing advances in generative artificial intelligence (AI) to enhance human-robot interaction is one potential approach to address this need. To date, few behavioral and social researchers applying for small business/tech transfer grants in this field have been successfully funded.

This concept aims to support small business projects that iteratively develop and test a social robot for use in dementia caregiving. Projects will use AI to develop and integrate multimodal sensory (e.g., vision, audio, haptic) and speech models to improve human-robot interaction.

Scientific/Research Contact:

Dinesh John, Ph.D.
Division of Behavioral and Social Research
Email Dinesh John

Rajesh Kumar, Ph.D.
Office of Strategic Extramural Programs
Email Rajesh Kumar

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Modeling Aging Through Microphysiological Systems

The majority of basic aging research and early-stage drug development has been conducted using static cell cultures and animal models that only partially mirror aging in humans. Microphysiological systems (MPS) — in vitro, three-dimensional (3-D) constructs that mimic human tissue or organ functions — could provide relevant and cost-effective models to complement two-dimensional cell cultures and animal models. While more than 30 companies are currently developing and commercializing a variety of MPS, none on the market to date include an aging component.

This concept will invite small businesses currently working in the MPS space to create self-contained systems that maintain 3-D tissue constructs to allow for human-relevant modeling of molecular and cellular aging processes and/or drug discovery for aging-related diseases. The MPS fabrication procedure should be cost-effective, mass-producible, modular, and robust to ensure successful commercialization.

Scientific/Research Contact:

Jennifer Fox, Ph.D.
Division of Aging Biology
Email Jennifer Fox

Rajesh Kumar, Ph.D.
Office of Strategic Extramural Programs
Email Rajesh Kumar

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Access and Manipulation of Brain Cell Subtypes Implicated in Aging and AD/ADRD

Recent advances in technology, driven largely by the NIH Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, have generated sophisticated cell-type specific access tools that pair breakthroughs in adeno-associated viruses (AAV) capsid engineering and enhancer element identification. These AAV-enhancer tools allow various cargos to cross the blood-brain barrier and target specific brain cell types with extreme precision in animal models. Previous NIA-funded Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) studies have uncovered and identified disease-associated gene signatures and alterations across multiple brain cell subtypes. Despite this rapidly advancing knowledge, it is still not clear how these changes contribute to brain cell dysfunction.

This concept will encourage the utilization of this powerful new AAV-enhancer technology to develop novel brain cell-subtype specific targeting approaches to explore mechanisms related to aging and dementia across brain cell subtypes. This concept proposes two phases. The first phase will focus on identifying targets, generating AAV-enhancer vectors, validating cell subtype specificity, and demonstrating effective in vivo brain transduction in an animal model. Only projects that successfully complete the first phase will move on to the second phase. The second phase will test the specificity of brain cell subtype targeting of the AAV tools in vivo and activity of the transgene(s), address mechanistic hypotheses related to aging and/or dementia in an animal model, and evaluate the expression profiles of the AAV vectors.

Scientific/Research Contact:

Erin Gray, Ph.D.
Division of Neuroscience
Email Erin Gray

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Alzheimer’s Drug Development Program – Renewal

In 2006, NIA launched the Alzheimer’s Drug Development Program (ADDP) as a major funding vehicle to support the most challenging and costly steps of preclinical drug development and seamlessly connect promising drug targets to first-in-human testing. NIA’s large-scale target and biomarker discovery programs and translational centers have successfully expanded the drug discovery target landscape and created a need for next-generation brain imaging compounds as essential tools in this effort.

This concept proposes to renew the ADDP and strengthen its ability to expand the number of investigational new drug (IND) candidates for emerging therapeutic targets; diversify the therapeutic pipeline for AD/ADRD with drug candidates targeting multiple underlying disease mechanisms that can be used as mono-therapy or as part of combination therapy; and enable a precision medicine approach to drug development by delivering INDs for PET ligands that can be developed into companion diagnostics. The ADDP will continue to support mid- and late-stage preclinical development for small molecules and biologics. The renewal of the ADDP will also provide support for novel brain imaging tracers for emerging drug targets that have potential to be developed into companion diagnostics.

Biomarkers of Cognitive Decline and Dementia in Individuals with Autism Spectrum Disorder

Over the past two decades, research exploring the link between dementia and Down Syndrome has provided insight on the impact of age-related neurodegenerative processes and cognitive decline in individuals with neurodevelopmental disorders. Recent epidemiological data suggests that people with autism spectrum disorder (ASD) may be at higher risk for dementia compared to the general population. However, very little is known about this area of research and adults with ASD are mostly overlooked in aging research studies. Currently, NIA does not have an active program in this space.

This concept aims to help fill that gap by supporting the establishment of observational studies and clinical cohorts of adults living with ASD, with particular interest in neuroimaging, molecular and other approaches to discover and characterize the trajectories of new biomarkers of neurodegeneration and their relation with age-related decline in multiple cognitive domains. The concept may also support evaluation of established dementia biomarkers in this population, development and validation of needed neuropsychological tools, and post-mortem studies to characterize markers of neurodegeneration and/or processes contributing to neurodegeneration.

Deciphering the Impact of RNA Modifications on Brain Aging and AD/ADRD

Emerging evidence indicates that RNA modification is highly regulated in the brain and that dysfunction in this area is linked to neurodevelopmental and neurodegenerative disorders, including Alzheimer’s disease. However, the regulation of RNA modification and its relationship to brain and neurodegenerative diseases is not well understood. New insights into the underlying mechanisms of RNA modifications will inform new strategies for estimating Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) risk, predicting disease trajectory, enabling drug development, and ultimately paving the way toward precision medicine.

This concept aims to support innovative research to characterize molecular details and functional impact of RNA modifications and to discover new RNA modification-mediated mechanisms, biomarkers, and therapeutic targets in brain aging and Alzheimer’s and related dementias. Research areas of interest include 1) identify functionally relevant RNA modification sites and genes linked to AD/ADRD; 2) investigate temporal and spatial dynamics of RNA modifications driving brain aging and AD/ADRD; 3) characterize RNA modifying machinery and identify cellular location and function of these proteins; 4) dissect cellular and molecular mechanisms of RNA modifications associated with the onset, progression, and severity of AD/ADRD and in brain aging; 5) identify RNA modification signatures that can potentially serve as biomarkers; and 6) explore therapeutic interventions interfering with RNA modifications and RNA modifying protein-mediated molecular pathways and cellular processes.

Facilitating T1 Translational Aging Research: Preclinical and Early Phase Humans Studies

T1 translational aging research, meaning the application of basic and clinical biomedical findings towards the development of new therapeutics for age-related conditions, continues to evolve. This area of research has generated promising insights for new and repurposed drugs, but few ideas have advanced beyond the discovery phase. Thus, there is a critical need for greater innovation and efficiency in translational research to accelerate clinical testing of novel interventions. While previous efforts have largely relied on traditional methods, there is growing interest in computational approaches.

This concept aims to accelerate progress in novel drug development and drug repurposing through multidisciplinary collaboration and innovation in computational techniques. It will support two project categories: a) conventional pathways and b) data-driven computational approaches with subsequent validation in animal and/or human experimental systems. Projects may involve collaborations with academic, nonprofit, or commercial entities. Possible topics include, but are not limited to:

• Development of novel treatments for age-related conditions such as sarcopenia, physical functional impairments, immunosenescence, fibrotic conditions, chronic obstructive pulmonary disease, chronic kidney disease, and wound healing
• Data-driven computational approaches for drug repurposing using heterogenous data resources
• Geroscience-based translation approaches including either computational drug repurposing studies or development of drugs to target fundamental mechanisms of aging.

The Impact of Stressors on the Biological Mechanisms of Aging and Other Aging-Associated Outcomes In Experimental Model Systems

The hallmarks of aging represent molecular, cellular, and systemic changes that underlie and drive the aging process. Until recently, the majority of studies examining changes in the hallmarks of aging and its downstream effects have been conducted in model systems under highly controlled conditions with minimal perturbations. However, both humans and animals experience multiple and repeated exposures to stressors over and across the lifespan, and these exposures likely impact the aging process. The impacts of stressors have largely escaped consideration in these studies; and in rare instances when stress is factored into a study, the focus is usually on acute exposures and short-term outcomes.

As a first step toward integrating research on the role of stress into studies on the biology of aging, this concept will solicit biphasic applications that focus on investigating the impact of stress exposures during the post-development period (“adulthood”) using in vitro systems, laboratory animals, and/or well-characterized wild, captive, or domesticated animal populations. The exploratory phase will aim to identify physical, social, and/or environmental stressors that, when initiated during adulthood, result in measurable changes in one or more hallmarks of aging. The implementation phase will expand upon the first phase studies to determine the impact of identified stressors on lifespan, health span, resilience to further or other stressors, and/or interactions with an intervention (pharmacological, behavioral, or genetic). The proposed funding opportunity will encourage comparative studies and will require multidisciplinary teams with expertise in both stressors/stress responses and the molecular, cellular, genetic, and biological mechanisms of aging.

Investigating Mitochondrial-Nuclear Communication in Brain Aging and AD/ADRD

Mitochondria are the major energy creator of the cell and their dysfunction has been linked to multiple age-related conditions, including Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). Mitochondria require a variety of proteins from other parts of the cell to complete their important biological functions, and most mitochondrial proteins are encoded by DNA in the cell nucleus. Despite this interconnected nature, little is known about how the mitochondria and nucleus communicate to ensure proper function and cellular health, and how metabolic changes caused by age and disease may impact this communication.

This concept aims to help stimulate the emerging field of organelle communication and will help provide foundational information and improved tools and methods to further study the role of nuclear-mitochondrial communication in aging and AD/ADRD. This concept would allow researchers to collect preliminary data on nuclear-mitochondrial communication, particularly using emerging tools and technologies. Researchers will be encouraged to investigate questions including, but not limited to:

• Do AD/ADRD risk factor genes show altered expression with mitochondrial dysfunction?
• How does mitochondrial dysfunction impact epigenetic changes to AD/ADRD genes?
• What is the functional consequence of epigenetic changes associated with mitochondrial dysfunction?
• Do different cell types exhibit different expression profile changes? Is there communication between peripheral cells?
• What role does mitochondrial heteroplasmy play in mito-nuclear communication?

Mentored Career Enhancement Awards to Build Cross-Disciplinary Knowledge and Skills for Comparative Studies of Human and Nonhuman Primate Species with Differing Life Spans

Comparative primate research is an important area of aging science that holds promise for identifying potential interventions to extend human health span in ways that may not be possible through human studies alone. Comparative primate research on life span and health span requires experience and expertise across multiple scientific disciplines. However, it is often difficult for mid-career investigators to establish new multidisciplinary collaborations, and to gain new training skills and resources required for developing and conducting rigorous research in this area.

To enhance research capacity and expand the community of researchers in comparative primate research, with a focus on longevity and health span, the proposed concept aims to facilitate cross-training and skill development for mid-career investigators. Specifically, this concept will support training activities that provide researchers with essential skills in a substantively different area of study than their current field of study, to enhance their capabilities to lead future comparative primate research projects. Examples of these projects include, but are not limited to the following:

• Examining the relationship between quantitative trait levels and lifespans in various primate species.
• Comparing biodemographic and life history characteristics of primate species and their impact on species lifespan.
• Analyzing the influence of cross-species differences in behavioral and social factors on primate life histories and lifespans.
• Investigating the effects of genomic changes during primate evolution and their potential impact on species lifespans.
• Studying variations in primate species’ interactions with environmental exposures.
• Exploring differences in age-related pathologies and their progression rates among primate species.
• Assessing the links between differences in brain regions and neuroanatomical features among primate species, their lifespans, and the risk of neurodegenerative conditions, including Alzheimer’s disease
• Developing and validating measures for cross-species comparisons in primates.

Scientific/Research Contact:

Carol Nguyen, M.S.
Division of Geriatrics and Clinical Gerontology
Email Carol Nguyen

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Renewal of the Claude D. Pepper Older Americans Independence Centers (OAICs)

The OAICs are NIA’s centers of research excellence on maintaining or restoring independence in older adults. Each OAIC develops programs that focus and sustain progress around a theme representing a key area of aging research for substantial populations of older persons and offers training opportunities in aging research. The OAICs have a long history of publications, multi-site clinical trials, successful pilot studies that developed into full-scale research awards, and collaborations.

This concept aims to continue the OAIC program within its current scientific scope, but with increased emphasis on expansion of diversity at multiple levels across the program. These include encouraging collaboration with minority-serving institutions, requiring a Diversity, Equity, Inclusion, and Accessibility plan beyond the Research Education Component (REC) program plan, and standardizing reporting procedures for REC participants.

Renewal of the Grants for Early Medical/Surgical Specialists’ Transition to Aging Research (GEMSSTAR) program

Ensuring an adequate pipeline of clinician-scientists, especially those in specialty fields, is critical for addressing the needs of a growing population of older Americans with complex medical problems. However, the intensive clinical training required of clinician-scientists in medical, surgical, and dental specialties often interferes with opportunities to develop a strong scientific track record. This can create a competitive disadvantage compared to non-clinician investigator peers. Established in 2011, the NIA GEMSSTAR program supports promising physician- and dentist-scientists at a crucial early career stage to help generate pilot data, obtain education and training in aging research, and establish a track record in aging/geriatrics-focused science in order to enhance competitiveness for subsequent funding. The GEMSSTAR Award funds a small research project alongside a separately funded individualized Professional Development Plan to augment skills in aging research and geriatric medicine. Participation in the Clin-STAR Annual Meeting during the award period is an integral part of the grantees’ experience and promotes collaboration, networking, career development and mentoring opportunities.

This concept aims to continue the GEMSSTAR program within its current scientific scope. It will help talented clinician-scientists establish a track record in aging research, build relationships with NIA and medical and surgical specialty societies, fund small research projects in their specialties, and promote interdisciplinary research among institutions.

Short Courses on Utilizing the NIH Stage Model to Develop Behavioral Interventions to Promote Healthy Aging

NIA supports research on behavioral interventions to help individuals meet the challenges of aging and to adopt behaviors likely to lead to improved health. NIA’s behavioral intervention development research program is guided by the NIH Stage Model , which is a six-stage intervention development framework that encourages a focus on understanding “how and why” interventions exert their effects all throughout the intervention development process. Understanding how and why interventions work, sometimes called the principle(s) or mechanisms of behavior change (MoBCs) of an intervention, is meant to create potent interventions that can be implemented efficiently in the settings where they are needed.

These short courses will develop curricula that address key elements of the NIH Stage Model. Specifically, courses will be asked to address, interactively, six behavioral interventions research topics essential to a full understanding of the Model: 1) NIH Stage Model Goals, 2) Stages, 3) MoBCs, 4) Fidelity, 5) Methodology, and 6) Scalability. Successful courses will equip investigators to use the NIH Stage Model in their own intervention development research, across a wide variety of theories, research designs, measures, and statistical approaches.

Short Courses Promoting Cross-National Analyses Using Data from the International Health and Retirement Study (HRS) and Harmonized Cognitive Assessment Protocol (HCAP)

NIA has made substantial investments in cross-national research on AD/ADRD through its support for the HRS International Family of Studies and the Harmonized Cognitive Assessment Protocol . Despite NIA’s substantial investments in this area, cross-national analyses of the HRS cognitive data and HCAP data, which could further our understanding of how different social, cultural, and institutional factors affect the trajectory of AD/ADRD in different contexts, have been relatively limited thus far. More needs to be done to support use of these valuable resources for transdisciplinary behavioral and social research related to aging and AD/ADRD outcomes.

This concept aims to support development of short training courses to increase utilization of the HRS cognitive and HCAP data. This project will develop training for scientists from multiple disciplines to improve skills in cross-national comparative research of HRS cognitive and HCAP data on a variety of aging and Alzheimer’s disease and Alzheimer’s disease-related dementias topics.

Scientific/Research Contacts:

Minki Chatterji, Ph.D.
Division of Behavioral and Social Research
Email Minki Chatterji

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Understanding the Mechanisms Underlying Age-Related Changes in Gait Biomechanics and Increased Metabolic Cost of Walking

Over 25% of older adults walk more slowly and exert more energy walking (metabolic cost) as they age, which can severely limit independence and quality of life. A combination of age-related changes in muscle strength, bioenergetics, balance, and joint mobility can contribute to this decline. The multiple factors and underlying mechanisms that affect walking speed, metabolic cost, and fatigue are not well understood.

This concept aims to support studies to better understand these mechanisms at the molecular level. It will encourage interdisciplinary collaborations that explore interactions among multiple systems and innovative approaches such as computational modeling, imaging and sensor technologies. Areas of interest include:

• Mechanisms and effects of central nervous system changes
• Neuromuscular changes
• Skeletal muscle bioenergetics
• Computational modeling and simulation
• Changes in tissue structure and function

NIA Aging Cell Repository — Contract Renewal

For 50 years, NIA has maintained the Aging Cell Repository as a scientific resource. The repository selects, produces, characterizes, and distributes more than 3,000 unique cell lines. Most cell lines are from humans, with others from nonhuman primates (NHPs), rodents, and domestic animals. It also includes cell collections from human longevity studies. The repository is a valuable resource for investigators performing functional and gene expression studies, characterizations of gene function and the effects of mutations, disease modeling, and as controls for assay development. The use of repository cell lines has resulted in 154 publications between 2020-2022 and more than 100 publications in 2023.

This concept proposes the renewal of a contract to ensure the continued availability to the research community of cell lines and DNA. The existing human geriatric collections will be reviewed to explore opportunities to enhance their value. The recent recognition and prioritization of NHPs as a highly valuable human-relevant animal model to investigate the biology of aging drive the plans to establish a biorepository of peripheral blood lymphocytes collected longitudinally and cross-sectionally from NHPs. A subset of these cells will be reprogrammed into a collection of induced pluripotent stem cells and linked to data from the NIA Primate Aging Database.

Pathology Monitoring of Aged Rodent Colonies

Mice and rats have long been used as animal models for aging research because they are more closely related to humans than yeast, flies, or worms, and they are easier to study than other mammals because of their relatively small size and short life span. NIA supports biomedical research that requires mice and rats to model the aging process through contracts that maintain colonies of aged mice and rats and ship them to funded investigators across the nation. To ensure the quality of these colonies and related research, it is essential to strictly monitor their health status to prevent the spread of pathogens to other animal facilities. It is also critical that investigators are aware of any non-life threatening pathogens detected in the colony to ensure appropriate housing at their facility and to accurately interpret their experimental data.

The goal of this contract renewal is to continue to provide independent monitoring of NIA’s aged mouse and rat colonies. In addition to providing the above health assurances, this will also inform program evaluation and help gauge performance of NIA’s rodent colony contracts. On a quarterly basis, a new batch of mice and rats from each room that houses the animals will undergo diagnostic tests to evaluate their health status. Tests include physical exams, tests for viruses and bacteria, a complete necropsy, and screenings for parasites and pathogenic protozoa.