NIA - National Institute on Aging Grants

NIA - National Institute on Aging

ABSTRACT ICU admission is a major life crisis that can result in severe distress for the patient's family, both during and after the hospitalization. This includes psychological distress such as anxiety and posttraumatic stress and also spiritual distress, including crises of meaning, purpose, or religious faith. Facing life and death decisions as the surrogate decision maker or experiencing the patient's death further increases distress. Prior interventions to support ICU surrogate decision makers have affected end of life care such as ICU length of stay for patients who die during hospitalization, but few have impacted surrogate well-being. We propose that for an ICU intervention to improve surrogate well-being, it must provide intensive spiritual and psychological support. Healthcare chaplains are highly trained professionals who provide spiritual and emotional support to patients and family members of all faiths and those with no faith affiliation in the healthcare setting. Chaplains are trained to listen deeply to an individual's religious and cultural experiences, providing opportunities to improve the care of marginalized groups who have faced discrimination in healthcare. Connecting religious or spiritual concerns and medical decisions also is a chaplain's skill. Although chaplains are part of the healthcare team in many US ICU's, research about the outcomes associated with chaplains' spiritual care is just emerging, and nearly all available randomized trials examined the effects of chaplains on patient outcomes. To address the need for interventions that reduce surrogate distress, our team has developed the Spiritual Care Assessment and Intervention (SCAI) Framework, an intervention for ICU surrogates that is rigorous, reproducible and consistent with spiritual care standards of practice. Our prior, single site randomized trial of the SCAI framework in the ICU demonstrated improved spiritual and psychological well-being for ICU surrogates in the intervention group, but the study population lacked religious and ethnic diversity. We now propose an NIH Stage 3 multi-center, randomized, attention controlled clinical trial of the SCAI Framework for surrogates to evaluate efficacy in a sample with geographic, religious, racial and ethnic diversity. The study will take place in 6 geographically diverse sites that are also diverse in terms of religion, race and ethnicity. The intervention will be delivered by skilled and highly trained chaplains. Specific aims are: to demonstrate the effects of chaplain- delivered spiritual care on psychological and spiritual outcomes including anxiety, distress, spiritual well-being, posttraumatic stress symptoms and complicated grief; to demonstrate the impact of chaplain-delivered spiritual care on medical decision making; and to examine the effects of spiritual care among historically underserved racial and religious subgroups. Results will guide hospital leaders, policy makers and the healthcare team regarding chaplains' role in improving surrogates' psychological and spiritual health and the quality of decisions for critically ill patients.

NIA - National Institute on Aging

PROJECT SUMMARY Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) are leading causes of morbidity, mortality, and excess healthcare costs. Care for AD/ADRD patients requires multiple providers, often hindered by fragmented communication. As treatment options continue to expand and an aging population with frequent comorbidities, challenges in care coordination will multiply and represent an urgent need in healthcare. In our prior work we have found that digital tracings of communication network structures identified within the Electronic Health Record (EHR) predict cancer patients’ outcomes (e.g., ED visits, mortality), hence we are developing scalable EHR tools to improve cancer patients’ care. Our results in cancer provide a strong foundation for studying AD/ADRD patients, given similarities in the complexity of care coordination across multiple providers and specialties. This study of persons with AD/ADRD expands on our prior work in cancer by factoring in the longer-term nature of AD/ADRD patient care and adding a significant new dimension to the care team: patient and caregiver communications via EHR patient portals. We will leverage social network analysis, machine learning (ML)-assisted visual analytics, and qualitative methods to study EHR communication structure data at three University of California health systems that all use Epic. Pilot analyses identified N=30,523 AD/ADRD patients with over 2.7 million patient/caregiver portal messages and 108,709 healthcare providers asynchronously accessing their digital records. We focus on one modifiable dimension of team communication, information sharing via EHRs. Aim 1: Develop the first multisite database of EHR multiteam system communication in AD/ADRD care, incorporating novel social network measures to describe and quantify within- and between-group collaborative patterns in intricate EHR interactions. Aim 2: Analyze the association between targeted EHR communication structures and quality outcomes through social network analyses, focusing on preventable ED visits and unplanned hospitalizations in AD/ADRD care. Aim 3: Utilize machine learning-assisted techniques to characterize and assess collaborative care dynamics, identify EHR communication structures associated with poor quality outcomes, and predict patient outcomes and events. Aim 4: Apply qualitative methods to deepen our understanding of the findings from Aims 1-3, exploring how and why communication structures and teaming patterns impact collaborative care delivery. Multisystem healthcare teams and communication structures need to be understood and then designed much more intentionally and based on evidence. Our innovative methods will provide data to help us improve our fragmented healthcare system and ensure quality care.

NIA - National Institute on Aging

Project summary/abstract It is well-understood that life-relevant changes in independence occur as early warnings of lost cognitive resilience, and eventually Alzheimer's Disease and related dementias (ADRD). We and others demonstrated that medication self-administration (MSA) provides exactly the opportunity needed for early identification of ADRD. However, several knowledge gaps hinder routine assessment of this critical health self-management skill in current care. We lack studies directly comparing self-reported measures and objective, convenient MSA assessments in the general population. In addition, the impact of CVD and cognitive risk factors on MSA errors and MSA overestimation, strong predictors of memory performance and daily life functional independence, is unclear. To address these challenges, we propose to perform an objective MSA assessment in the Framingham Heart Study. This cohort has well-characterized cognitive assessment for up to three decades. An estimated 1185 surviving participants from the second-generation and Omni 1 Framingham Heart Study cohorts are expected to participate as part of their 11th /6th comprehensive health examination, starting September 2025. Our central hypothesis is that MSA errors and self- overestimation are early indicators of disabling brain and behavior changes. In Aim 1, we will cross-sectionally associate MSA errors and MSA self-overestimation, using the Hopkins Medication Schedule and a visual vertical scale, with behavioral- (neuropsychological performance) and brain-based ADRD biomarkers (atrophy, white matter change). In Aim 2, we will associate MSA assessment with a trajectory of cognitive decline on the Mini-Mental State (MMSE) and neuropsychological testing, as occurs in ADRD. In Aim 3, we will establish whether MSA assessment predicts greater care needs and life-relevant disability, examining the Allocation of Caregiver Time Survey, ER visits and hospitalizations, physical activities, and physical performance. MSA assessment is brief and feasible, with potentially greater public health value value than standard generic cognitive screening. We expect that our study will establish a role for objective MSA assessment in geriatric and cognitive care, and we also expect our research results to improve the MSA assessment standard used in pharmaceutical trials that enroll the aged.

NIA - National Institute on Aging

Aging

NIA - National Institute on Aging

Project Summary Alzheimer’s disease and related dementias (ADRD), rank as the fifth-leading cause of death for Americans over age 65 and have no known treatments to prevent or cure. Physical frailty, a syndrome of physiological systems declines among individuals aged 65 and older, is recognized as a risk factor for cognitive impairment that is predictive of ADRD. Understanding the shared mechanisms for both physical frailty and ADRD is crucial for enhancing and understanding the link between these two complex and multifactorial conditions. Existing studies have focused only on a few inflammatory biomarkers involved in physical frailty and cognitive impairment. Few studies have comprehensively investigated the role of inflammation underlying physical frailty and ADRD by utilizing multi-omics data, which also allows for integrated analyses of other shared mechanisms and their interplay with inflammation. As high-throughput proteomics, circulating immune cell abundances, and metabolomics data are becoming more accessible, as well as employed with advanced data integration and artificial intelligence /machine learning (AI/ML) approaches, the proposed F99/K00 will be the first to explore the impact of a broad panel of inflammatory markers that link physical frailty and ADRD, extending the investigation beyond inflammation alone. The specific aims of this study are to: 1) establish frailty-implicated inflammatory signatures associated with cognitive decline and/or dementia risk, aiding in ADRD risk assessment (F99 phase); and 2) characterize the molecular basis among different biological components (multi-omics data) linking physical frailty and ADRD, with a focus on inflammation and relevant pathways (K00 phase). During my dissertation phase, I will train in multi-omics integrative analysis methods, machine learning, and predictive modeling, to develop frailty-implicated inflammatory signatures and examine the signatures as risk factors for ADRD. I will develop data integration methods that both incorporate cohort heterogeneity and are transferrable across cohorts to improve association detection and prediction accuracy. As a post-doctoral fellow, I will expand my training to ADRD pathogenesis leveraging multi-omics data and AI/ML-driven multimodal approaches to understand shared mechanisms underlying the link between physical frailty and ADRD including inflammation and relevant processes. This research will leverage the Framingham Heart Study, under the direction of the National Heart, Lung, and Blood Institute, and UK Biobank, including longitudinal cohorts with large-scale multi- omics data, physical frailty phenotypes, and surveillance for ADRD onset. This fellowship application aligns with NIA’s strategic goal D-2, “to identify and understand the genetic, molecular, and cellular mechanisms underlying the pathogenesis of AD/ADRD and other neurodegenerative disorders of aging.” As a result of this work, we will identify shared biological pathways, including inflammation, that contribute to the progression of physical frailty and ADRD, offering promising targets for ADRD early detection and intervention. This award will train me as an independent investigator launching a career in making novel contributions to ADRD pathogenesis and prediction.

NIA - National Institute on Aging

This application seeks funding to continue a series of international and interdisciplinary research conferences on cognition, speech communication and aging. Scientists approaching this problem have typically been working in the areas of sensory and perceptual processing, especially hearing, cognitive psychology, or auditory neuroscience. Aging can have a negative impact on all of these systems and understanding how deficits in these areas, both independently and combined, affect speech understanding requires cross- disciplinary understanding and collaboration. We have developed a set of learning objectives for the conference and we currently have agreements from leading national and international researchers for oral presentations addressing these objectives (1) age-related changes in auditory perception and physiology; (2) animal studies of aging and hearing; (3) age-related changes in speech production, perception, and understanding; (4) cognition and aging; (5) multi-sensory perception and aging; (6) hearing loss and assistive devices; and (7) technical advances. In addition, we have requested funds to provide student scholarships to promote and support early-stage investigators. An important aspect of the conference is to encourage early- stage investigators in hearing research. By bringing together scholars actively involved in research across the disciplines, it is hoped that further progress will be made in understanding and remedying the speech- communication difficulties of older adults.

NIA - National Institute on Aging

Project Summary The impact of reproductive events on menopause and aging processes is largely unknown. While menopause is part of the aging process, the timing of menopause varies with earlier onset associated with risk of premature mortality. Latina women’s timing and frequency of reproductive events, including puberty, pregnancy, and menopause, differs from that of other racial/ethnic groups. Despite socioeconomic disadvantage, on average, Latina women experience similar or lower risk of adverse birth outcomes compared to non-Hispanic white women. This so called “birth paradox” does not apply to maternal outcomes. Latina women in the US have an elevated risk of primary cesarean, gestational diabetes, and increased risk of developing type II diabetes and heart disease later in life. We propose to examine how reproductive events are associated with biological aging processes and menopause and how social context may modify these associations in a sample of Latina women participating in the Hispanic Community Health Study /Study of Latinos (HCHS/SOL). The HCHS/SOL study is a longitudinal study of US Latinos, representing varied countries of origin, conducted in the US. The planned analyses will be conducted among a random sample of pre-menopausal women at baseline followed over a 12-year period. Leveraging the infrastructure of the HCHS/SOL study, through a brief phone-call, we will collect detailed information on reproductive events, perimenopausal symptoms and timing of menopause. We propose to assay existing blood samples for DNAm and characterize trajectories of epigenetic aging over a 12-year period (three time points) to understand how reproductive events influence timing of menopause and DNAm age in adulthood among Latina women. Uniquely, this design allows us to compare individuals’ DNAm aging pre- and post- reproductive events, a major strength of this proposal. Specifically, we will examine 1): How the frequency, severity and timing of reproductive events (menarche, infertility, pregnancy complications and gynecological disorders) affect menopausal onset and symptoms (N= 2000) and how social context may modify this association; 2) How frequency, severity, and timing of reproductive events impact the rate of epigenetic aging among premenopausal women of late reproductive age followed over a 12-year period to capture the menopausal transition (N=1000) and how social context modifies this association; 3): Use genome wide methylation and functional enrichment analyses we will explore how reproductive events are related to alterations of DNA methylation, prior to and during the menopausal transition (N=1000). Upon completion of this project, our findings will elucidate important epigenetic pathways that will help explain how reproductive events affect aging processes among a population that experiences distinct sociocultural factors.

NIA - National Institute on Aging

Project Summary Adult hippocampal neurogenesis represents one of the most transformative yet contested concepts in neuroscience. While robustly demonstrated in rodents and other mammals, including non-human primates, the existence, extent, and functional relevance of neurogenesis in the adult human brain remain unresolved. Confirming adult hippocampal neurogenesis in humans would profoundly reshape our understanding of brain plasticity, resilience, learning, and memory, and inform new therapeutic strategies for neurodegenerative and psychiatric disorders. However, conflicting evidence from isotope-labeling, immunohistochemistry, transcriptomics, and cell culture studies—paired with challenges in postmortem tissue analysis and methodological reproducibility—have fueled intense debate within the field. This Banbury meeting will convene leading experts from multiple disciplines to critically assess the current body of evidence, including leaders who have recently generated new unpublished data to support or defer the presence of human neurogenesis, evaluate the potential of emerging methodologies such as spatial transcriptomics and single-cell analysis, and chart a collaborative path forward. Specific aims include: (1) critically evaluating existing data and technical limitations, (2) identifying promising technologies for resolving key questions, (3) fostering interdisciplinary collaborations, and (4) defining strategic priorities and standards for future research. The meeting will culminate in a consensus report that outlines current knowledge, identifies gaps, and provides actionable recommendations to guide the field. By bridging experimental, technical, and conceptual divides, this effort aims to resolve one of neuroscience’s most pivotal questions and advance our understanding of human brain function and plasticity.

NIA - National Institute on Aging

PROJECT SUMMARY In order to address the health and well-being problems posed by an aging population in the United States, research that pinpoints how to protect aging adults from health risks is needed. To enable rigorous, high-quality research in this area, two scientific approaches are necessary. A lifespan approach addresses the fact that aging is a complex, dynamic, cumulative process that unfolds across time. A biopsychosocial approach addresses the fact that psychological and social factors interact with physiological factors to drive aging. Work that integrates lifespan and biopsychosocial perspectives requires both scientific understanding across disciplines and also requires knowledge in strategic collaboration, scientific leadership, effective communication, and project management. The Society for Biopsychosocial Science and Medicine (formerly the American Psychosomatic Society) has integrative work as its very mission, and across 82 meetings has been where cutting-edge research combining biological factors with psychosocial factors is presented. However, lifespan approaches have not been traditionally centered at the meeting. Therefore, we will pursue aims under the conference theme of Biopsychosocial Science and the Future of Health and Well-Being Across the Lifespan. First, we aim to provide methodological, content, and career development training to prepare junior scholars for a career in biopsychosocial lifespan research. We will do so by supporting a mentorship program called the Developing Investigator Program—a mentorship program for promising trainees where senior members with a history of external funding are matched with each junior investigator to provide mentorship and concrete feedback on a grant proposal. Second, we aim to advance science that elucidates the personal, interpersonal, societal, and environmental factors influencing aging. We will do so by providing programming highlighting the highest caliber biopsychosocial aging and lifespan research. For example, we will invite experts to provide scholar training sessions will provide concrete and actionable resources for scholars to engage in biopsychosocial lifespan aging research in HRS, MIDUS, and other NIA-funded longitudinal deeply phenotyped datasets. Based on empirical literature on mentorship, we are innovating on the traditional one-time events often offered at conferences to create infrastructure for two-year long relationships. The expected outcome of these endeavors is a scientific workforce trained in approaches that integrate across biology, psychology, and social factors to ultimately improve health and well-being throughout the lifespan. 

NIA - National Institute on Aging

Abstract Support is requested for a Keystone Symposia conference entitled “Aging: Immune Function and Organ Health,” organized by Drs. Anne Brunet, Eric M. Verdin, Manuel Serrano and P. Eline Slagboom, with scientific programming input from Keystone Symposia. The meeting will take place March 22–25, 2026 at the Fairmont Banff Springs in Banff, Alberta, Canada. Aging is the single largest risk factor for a wide spectrum of chronic diseases and mortality, and the immune system is emerging as a crucial player in regulating the human lifespan. Recent studies have revealed that aging can be influenced by changes in immune function and inflammation, offering new treatment approaches to counter aging and age-related diseases. This Keystone Symposia meeting will bring together an interdisciplinary group of researchers to address the impact of the immune system on organ preservation and organ-organ communication, which are critical for organismal longevity. This meeting will also highlight transformative technologies and discuss how engaging the immune system can create opportunities for therapeutic interventions that benefit human health. This meeting will be held jointly with another Keystone Symposia conference, “Innate Immunity: Diversity in Host Defense and Disease.” This partnership will provide valuable insights into the interconnected role of the immune system in aging, its relation to organ function, and implications for organismal health and disease.

NIA - National Institute on Aging

Cold Spring Harbor Laboratory Conference on Protein Homeostasis in Health and Disease April 21 - 25, 2026 ABSTRACT This proposal is a request for financial support for a meeting on PROTEIN HOMEOSTASIS IN HEALTH AND DISEASE to be held at Cold Spring Harbor Laboratory from April 21 - 25, 2026. This meeting is the premier international forum for presentation of new results in this exciting area across biology and medicine and is attended by representatives from virtually every major laboratory in the field. The explosion of new information on how the folded state of proteins is acquired and maintained in vivo and the relevance of this process to essentially all biological processes for healthy aging and risk for degenerative diseases of aging including neurodegeneration, cancer, and metabolism guarantees an excitement and urgency of this meeting. To honor the previous more-than-a-decade organizers and recognize their immense contributions to the field, Drs. Hartl and Morimoto, we will feature them in a keynote opening session. Because of the recent developments on stress signaling in aging and disease, we will next focus on cell stress response signaling, chaperone mechanisms and co-translational folding and ribosome quality control. We will then explore the roles of intrinsically disordered proteins and their roles in biological condensate formation, protein degradative mechanisms, and organellar proteostasis and spatial quality control in Aging and Disease. We will close with a session on protein misfolding and aggregation in aging as well as age-associated disorders, including Alzheimer's disease and ALS. The themes of aging, proteostasis failure, and diseases of protein misfolding are well integrated throughout each session, and emerging principles on protein client interactions and alternate protein conformations will be dominantly displayed. The diverse protein quality control strategies used by compartments of the cell to ensure the integrity of the secretory and organellar pathways during times of protein folding stress will be represented by emerging topics on spatial quality control within a cell. The field of heat shock proteins and molecular chaperones has grown exponentially and draws interest not only from traditional scientific disciplines in the basic sciences but also from diverse areas of biomedical research including neurodegenerative disease, infectious diseases, cancer, heart disease and aging. Overall, the meeting will have eight lecture sessions, two poster sessions, two lightning presentation sessions, a panel discussion on therapeutic approaches targeting proteostasis, and a daily lunch/mentoring session with the speakers. Each session will consist of eight to nine oral presentations. For each session, we have invited two speakers, who will also serve as co-chairs. The remaining speakers in each session will be selected from the submitted abstracts. All speakers will have 15 minutes talk time. In addition, each lightning sessions will have 10 pre-selected poster presenters, who will have the opportunity to highlight the key features of their work in 2-min talks. This balance of talks allows the meeting to feature presentations by leading scientists, to be responsive to exciting new developments, and to encourage participation from investigators new to this field.

NIA - National Institute on Aging

PROJECT SUMMARY This application seeks partial support for the upcoming Society for Muscle Biology (SMB) conference entitled, "Skeletal Muscle Stem Cells in Development, Regeneration, and Adaptations", which will be held July 19-24, 20256 in Victoria, BC, Canada. This will be the 13th edition of this conference since 1998 focusing on skeletal muscle stem cells (MuSCs) and the 2nd sponsored by the SMB. This biennial meeting has traditionally been operated by FASEB, but shifted in 2024 to be organized under SMB to allow the organizers and participants more autonomy. This change facilitates a more robust and vibrant conference and a greater focus on supporting trainees. We expect approximately 125 attendees from around the world with at least ~60% junior researchers. No other scientific meeting has a primary focus on MuSCs. The need for a conference with this focus is demonstrated by the steady increase in attendance since the meeting's inception and the consistently excellent post-meeting evaluations provided by meeting attendees. This meeting attracts all leading MuSC researchers from around the world, further demonstrating its value for established and future leaders in the field. The overall objectives of this meeting include to: 1) provide a comprehensive analysis of recent discoveries in the field, with the goal of understanding the regulatory mechanisms controlling normal and abnormal functions of MuSCs in muscle development, homeostasis, regeneration, hypertrophy, aging, and myopathy; 2) create and foster an interactive environment for the exchange of ideas and unpublished data, so as to hasten discoveries and facilitate new and existing collaborations; 3) provide opportunities for junior investigators to present their work and network with senior investigators; and 4) facilitate career development of all career stages by ensuring representation in all aspects of the conference program. Our keynote speaker will be Dr. Peter Zandstra, a renowned engineer and stem cell biologist. Scientific sessions are planned, presenting 48 speakers (23 confirmed invited speakers and at least 25 selected from submitted abstracts) at all career levels. Session topics include: (i) Molecular regulation of MuSCs; (ii) Spatial and modeling innovation in MuSC analysis; (iii) MuSC epigenetics and transcriptional regulation; (iv) Engineering and translating muscle stem cells; (v) MuSC dynamics during development and muscle regeneration; (vi) MuSC niche biology; and (vii) MuSCs and other cell interactions in disease. Invited speakers have been selected for their scientific excellence, with particular attention to discipline, encompassing all trainee levels and geographical diversity. Speakers are explicitly required to present unpublished work, to ensure scientific discussion is at the forefront of the field. We will have poster sessions, each preceded by a “posters blitz” where poster presenters will give a one-minute talk to highlight their work, and career-oriented workshops and “meet-the-speaker” breakfast and lunch sessions. This meeting will provide a forum to foster discussion and cross-fertilization from diverse areas of research, to advance our understanding of muscle regeneration and aid in the development of therapeutics.

NIA - National Institute on Aging

PROJECT SUMMARY/ABSTRACT There are currently 50 million people suffering globally with Alzheimer’s disease (AD). 95% of the population over age 65 is concerned about their dementia risk and 80% are interested in dementia screening. There is a critical need for accessible and cost-effective biomarkers that can be used to identify those on the ADRD continuum – including the asymptomatic stages – not only in research and specialty-care centers, but in community-based and primary care settings as well. This information could dramatically improve referrals for early clinical trial enrollment, the triage process for specialty evaluation, and comprehensive care planning. The methods used must be appropriate for point-of-care, community, or at-home deployment while maintaining accuracy and predictive value. Olfactory (sense of smell) dysfunction (OD), in combination with machine learning (ML) algorithms, is a promising non-invasive biomarker for ADRD. We have previously demonstrated the reliability of the Affordable Rapid Olfactory Measurement Array (AROMA) to objectively measure OD and categorize olfactory phenotypes (patterns of correct and incorrect responses to various odorants and multiple concentrations). AROMA uses essential oils, which are complex blends of odor molecules and may be more reflective of “real world” olfaction than the single chemicals used in most other tests. This is because when scents are encountered in real life, the brain processes and recognizes the odorant combinations making up each complete scent differently from the individual component chemicals. Our research with AROMA in ADRD has shown that AROMA can distinguish cognitively unimpaired (CU), mildly cognitively impaired (MCI), and AD patients from one another. Additionally, olfactory phenotypes were detected using machine learning and differentiated between disease states. Our algorithms had 100% sensitivity, 83% specificity for correctly classifying CU versus MCI/AD. Algorithms tasked with classifying MCI versus AD had 100% sensitivity, 75% specificity. We propose longitudinal testing of CU, MCI, AD subjects (n=324 men and women > 55 years) over 3 years to assess changes in OD, functional status, and neurocognition. A group of neurologic controls will be included to ensure olfactory phenotypes are specific for ADRD. Using traditional statistics and machine learning techniques to examine the relationship of AROMA performance with ATN-biomarkers and clinical markers of disease (Aim 1); define predictive models using AROMA data to predict changes in function and frailty (Aim 2); and develop a streamlined ADRD-version of AROMA using only the scents and concentrations of highest influence (Aim 3). Our long-term goal is for point-of-care olfactory biomarker data, analyzed in real-time by ML algorithms, to be widely accessible to meaningfully inform clinical, research, and caregiver decisions.

NIA - National Institute on Aging

PROJECT SUMMARY Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease affecting a total of 6.5 million Americans over the age of 65, with that number growing each year as our population ages. There is currently no prevention nor cure for AD, and only a handful of drugs that slow, but do not stop, the disease’s progression. The AD brain is marked by accumulation of amyloid β plaques, tau neurofibrillary tangles, and lipid droplets. Recent studies report brain and whole-body metabolic dysfunction in AD, to the extent that glucose insensitivity, insulin resistance, and metabolic hormone dysregulation are nascent hallmarks of AD. Additionally, metabolic syndromes such as type 2 diabetes, obesity, and hypertension are significant risk factors for the development of AD. The contemporary understanding of AD as a metabolic disorder has sparked a growing interest in metabolism-based therapy. One such therapy, the ketogenic diet (KD), a high-fat/low-carbohydrate diet, is increasingly being studied in the context of AD and has shown promise in preclinical and clinical trials. However, the potential of the KD as a treatment for AD is marred by variable efficacy, low compliance, and side effects outweighing benefits. The molecular mechanisms by which the KD ameliorates AD pathology are unclear and warrant further study, and potential mechanisms include inhibiting carbohydrate metabolism, increasing fat metabolism, and altering amino acid (AA) metabolism. My F99 phase (Aim 1) of this proposal will focus on β- hydroxybutyrate (BHB), the primary ketone body produced by KDs, which can act on the body in two main ways: metabolism for energy and signaling. I will disentangle these molecular features of BHB (1.1) in vivo via transgenic mouse models and (1.2) in vitro via orthogonal validation of candidate pathways identified in neuronal tau interactomics. My K00 phase (Aim 2) will expand to AAs, specifically looking at isoleucine (Ile) restriction and dissecting the effects of Ile on protein synthesis (2.1), signaling (2.2), and metabolism (2.3) in the context of AD and brain aging. The unifying goal of this F99/K00 proposal is to use the KD as a starting point for the development of novel metabolic therapies for AD and brain aging by (1) identifying the bioactive components of the KD that are necessary and sufficient for its benefits in AD and brain aging and (2) disentangling the convergent and divergent mechanisms of action of dietary metabolites in AD and brain aging. This F99/K00 proposal will enable my long-term goal of establishing an independent lab that applies pharmacological, genetic, and mass spectrometry approaches to dissect the molecular underpinnings of metabolic interventions in AD and brain aging.

NIA - National Institute on Aging

Project Summary In response to the growing number of people living with serious and life threatening illness, and the need to enhance the evidence base to improve clinical care, the American Academy of Hospice and Palliative Medicine (AAHPM) is convening the third State of the Science (SOTS) in Hospice and Palliative Care Research Symposium on March 2-3, 2026 in San Diego, CA. High quality clinical practice, supported by science, for people living with serious illness (SI) across the lifespan, especially the rising number of older adults, is critical. The number of Americans living with SI is increasing, including those with a combination of frailty, progressive physical and/or cognitive disabilities, multiple chronic illnesses, functional limitations,1 cancer, and children with illnesses that benefit from palliative care. The field of palliative care is uniquely positioned to address the needs and improve care for all people living with SI. Robust research and expertly trained scientists are needed to address critical knowledge gaps, which include best practices in promoting access, caregiving, and research methodology.2 The SOTS research symposium seeks to address the trans- NIH goal to support palliative care science across the lifespan3 by bringing together palliative care scientists from multiple disciplines representing medicine, nursing, social work, pharmacy, chaplaincy, rehabilitation therapy, psychology, health sciences, and others to facilitate research dissemination, mentorship, career development, and research collaboration to inform and address issues related to progression and prognosis of disease and disability. Target audience includes interdisciplinary researchers across career stages. The SOTS Planning Committee, made up of volunteers who are considered experts in their field, provide oversight of the planning and implantation and ensure scientific rigor, and will prepare a peer-reviewed report summarizing presentations and panel discussions at the research symposium. The report will examine scientific content and methods, highlight research gaps, provide recommendations for future research, and inform 2027 SOTS planning. The SOTS will be immediately followed by AAHPM's Annual Assembly of Hospice and Palliative Care, co-hosted by the Hospice and Palliative Nurses Association. This strategic scheduling makes it easier for researchers and practitioners to attend both events, reducing costs and travel time.

NIA - National Institute on Aging

PROJECT ABSTRACT Social isolation, loneliness, and social connection are gaining global attention due to their profound impacts on the health and well-being of older adults. In 2023, advisories by the Office of the Surgeon General, legislation introduced by United States Senator Murphy and Representative Flood, and a Commission on Social Connection by the World Health Organization (WHO) all demonstrated urgency in addressing an “epidemic” of loneliness and social isolation. Central to advancing the field is updating existing measures of social connection and developing better instruments for assessing social isolation and loneliness that can fully capture the experience of today’s older adults. This two-day scientific meeting is therefore focused on advancing the science of measurement of social connection for older adults through an interdisciplinary approach. It will further support early-stage researchers and nurture national networking and collaboration. The following aims are proposed: Aim 1) To identify priorities in what should be included in measurements across settings, populations, and evaluation goals; Aim 2) To advance a national agenda to address gaps in measurement across aging populations, creating a foundation for future discussions and conferences; and Aim 3) To provide mentorship to, and create community amongst, early-stage investigators focused on social connection research. The scientific meeting will bring together US-based researchers, decision-makers, and practitioners with expertise in social connection across varied scientific disciplines (e.g. social and health sciences) and interested parties (e.g. academia, community-based, policy, industry). Our approach will largely rely on a workshop format to enable open discussion on the major challenges and gaps in measurement across settings, priorities for aligning measures, and innovations in methods to gather data. We will support early-stage investigators through travel stipends, mentor-mentee pairing, and an aims workshop. In addition, we will generate clear recommendations for multiple interested parties through a peer-reviewed convening paper, a policy brief, and online materials. Taken together, the scientific meeting will serve as a critical starting point to advance the science of loneliness, social isolation, and social connection measurement among older adults. It will build meaningful national collaborations, support early-stage investigators, and inform measurement considerations for funders of social connection research. This conference will serve as a basis for future R13 applications to hold interdisciplinary national meetings, including around innovative interventions and technologies.

NIA - National Institute on Aging

Project Summary/Abstract The broad goal of this proposal is to understand how obesity interacts with the aging process and accelerates memory decline across the lifespan. Age-related memory loss occurs in ~33% of adults over the age of 70, yet no treatment option exists that can prevent or reverse these impairments. One of the major risk factors for developing age-related memory impairments is obesity, which affects nearly 40% of U.S. adults. However, even though obesity and aging are both known to be associated with cognitive decline, very little is known about how they interact to affect memory across the lifespan. The ubiquitin-proteasome system (UPS) controls the majority of protein degradation in cells and is dysregulated with age and in Alzheimer’s disease. However, the ubiquitination process is complex, and few studies have examined the role of degradation-independent ubiquitin modifications in the brain. K63 polyubiquitination is the second most abundant form of ubiquitination and is independent of protein degradation. We recently found that reductions in K63 polyubiquitination the hippocampus is critical for normal memory formation in young adulthood. Interestingly, we also found that both aging and obesity in young adult rats leads to aberrant increases in K63 polyubiquitination in the hippocampus, the primary brain region involved in long-term memory formation, which correlates with obesity- and age-related memory impairments. Further, knockdown of K63 polyubiquitination in the aged hippocampus rescues age-related memory deficits. However, it is unknown whether the obesity-induced and age-induced K63 polyubiquitination dysregulation are directly connected or instead just share some common molecular mechanisms. The work in this proposal is designed to test 1) if obesity accelerates age-related memory decline via dysregulation K63 polyubiquitination in the hippocampus, and 2) whether reducing aberrant increases in K63 polyubiquitination in the hippocampus can prevent obesity- and aging-induced memory decline. Using a diet-controlled longitudinal design in combination with sophisticated protein purification methods and unbiased mass spectrometry whole proteome analyses, Aim 1 will test if obesity accelerates the aging process in the hippocampus or instead results in a unique process characterized by dysregulated K63 polyubiquitination of a distinct subset of proteins. Aim 2 will use a diet-controlled longitudinal design in combination with cutting-edge CRISPR-dCas13-mediated knockdown of hippocampal K63 polyubiquitination to test if preventing obesity-induced and aging-induced increases in K63 polyubiquitination can preserve memory across the lifespan. Collectively, this study will answer important questions about how obesity can accelerate age-related memory decline and increase the susceptibility to age-associated neurodegenerative disorders. Results from this project could provide critical insights that may lead to the development of novel treatment strategies designed to mediate the effects of obesity on the aging process

NIA - National Institute on Aging

There is currently an approximate 60% success rate in diagnosing Alzheimer’s disease (AD) using cognitive tests. New FDA approved blood tests testing for amyloid plaque byproducts could soon bring this number to 90%, among patients with cognitive deficits. AD will now be detected earlier, and will consequently be more likely to be treated effectively. As amazing as these new indicators might be, effective treatments will still require an understanding of how the disease progresses, and how it affects the prefrontal and hippocampal structures, on a case-by-case basis. The ventral hippocampus (vHPC) is in bi-directional interactions with both the prefrontal cortex and the dorsal hippocampus (dHPC) and is likely to be an early locus of cognitive dysfunction. The traditional view is that vHPC and dHPC, even though they are part of the same anatomical structure, may perform different functions and that vHPC is much less involved in spatial navigation than dHPC. We propose that this view emanate from the fact that most of the studies in spatial navigation were conducted in relatively small environments where the large place fields of vHPC are not functionally relevant, because they do not discriminate between spatial locations (low position information content). Based in part on these findings, very little attention has been placed on the role of vHPC in normal or abnormal aging. In this 2-year proposal, we aim to fill this gap by characterizing the role of dHPC and vHPC in very large environments where the large place fields of vHPC are likely to be functionally relevant to spatial navigation. We further hypothesize that the encoding of space at both levels of the structure will be related to the complexity of the tasks. We propose to test these ideas by contrasting the multi-field and multi-scale neural encoding by place cells and the behavior of the animals in two tasks with low (foraging) and high (multi-goal maze) cognitive loads respectively. To measure the complexity of the multi-goal mazes, we propose to use the quantitative tools of Space Syntax, a common framework in Architectural Sciences that is rarely used in Neuroscience, if at all. We also propose to sample hippocampal activity in animals with increasing amount of experience and training, as in human aging, throughout their life span, starting from young adulthood until senescence. Whether differences in encoding between ventral and dorsal levels vary with complexity and age are observed or not, this study will likely provide important information and motivation for further studies of this and related structures not only in the context of spatial navigation in complex environments, but also in the manner in which they differentially processes simple and complex memories. Altogether, this proposal will advance our understanding to the role of the longitudinal axis of the hippocampus in complex spatial information processing and its changes as subjects age. It will shed further light of the contribution of this axis, as a whole, into the deficits observed during AD, dementia or mild Cognitive Impairments in humans.

NIA - National Institute on Aging

PROJECT SUMMARY This proposal seeks funding for 21 US-based Early Career Scientists (ECSs) to attend the FASEB Protein Folding in the Cell meeting in Louisville, Kentucky from June 1-4, 2026. This conference focuses on the latest developments regarding how the native conformations of cellular and secreted proteins are achieved and maintained. The meeting’s focus is on the basic science defining protein homeostasis, whose decline is especially prominent during aging and associated with many different neurodegenerative diseases, including Alzheimer’s disease and related dementias. Thus, we will dedicate close to half of the talks to this topic and pay particular focus on recent advances in therapeutic strategies. Special emphasis for the transmission of information will be placed both on the formal presentations as well as on informal interactions through round table discussions and, group brainstorming sessions to catalyze the generation of new hypotheses and the initiation of collaborations. Given the strong connection between protein folding and protein degradation and the fact that failure in either of these processes contributes to aging and disease, we are excited to report that we will, for the first time, join forces with the FASEB Ubiquitin (UB) meeting. We have precisely coordinated our two programs in an effort to provide maximal interactions. We will organize a joint Ignite Career Forum (see below), and will hold the keynote session, the poster sessions, two morning sessions (half of the speakers from UB, half from Protein Folding (PF)), and all coffee breaks, lunches, dinners and workshops together. By doing so, we will significantly expand the breadth of our covered topics and expose ECSs to a much broader research community while, at the same time, reducing the number of marquee speakers in the individual meetings and saving costs on registration. We will organize the second “Ignite Career Forum”, which will take place right before the main meeting, and will give sixteen graduate students and postdoctoral fellows the opportunity to present their research. The two best talks will be awarded speaking slots in the joint morning sessions of the main meeting. In addition, we have set aside 11 talks for invited ECSs and ECSs selected from the submitted abstracts, with a focus on bringing postdocs and Assistant Professors into the main program. Funding is sought to provide registration and travel awards for the 8 pre-meeting speakers (PF only), the two students representing PF on the organization committee as well as the 11 ECS, who will be selected for talks in the PF-program. We will organize 2-min lightning talks for poster presenters. Round table discussions over lunch will enable ECSs to discuss topics like careers, effective grant writing, how to pick the best research projects etc. with experts in the field.

NIA - National Institute on Aging

The 16th International Conference on Brain Energy Metabolism: “Preserving Cellular Energetics and Brain Function in Aging and Neurological Disease” will be held June 29-July 2, 2026, in Barcelona, Spain. Alterations in energy metabolism at the cellular and subcellular level and in neurovascular and neurometabolic coupling are key aspects of brain aging and Alzheimer’s disease, however, little is known regarding the mechanisms and interactions between poorly understood, yet critical aspects of energy metabolism. The goal of the 16th ICBEM meeting is to bring together leading experts in emerging techniques and researchers in clinical and basic neuroscience, and radiology who would not otherwise meet. The 2026 ICBEM meeting will serve as a driving force for cutting-edge discussions, formulation of incisive experiments, and for fostering collaborations to open novel areas of exploration related to alterations in energy metabolism that underlie and contribute to aging related diseases. To enhance interaction, the conference is limited to ~118 attendees and opens with a Keynote talk, by Thomas Longden, Ph.D. who will address the effects of metabolism in pericytes on cerebral blood flow in normal and aging brain. The conference is organized into a roundtable discussion, small group discussion, poster sessions, and 8 scientific sessions with 21 session speakers, 4 (19%) of which are early career investigators. The conference brings together experts as well as students and postdocs in a highly interactive forum with more than 33% of meeting time allocated for discussion of emerging concepts related to the regulation of neurovascular and neurometabolic coupling in normal and aging brain, neuronal-glial communication, alterations in lipid metabolism that impact cell function in aging or the presence of ApoE4, the roles and neuroprotective potential of alternative substrates, whether glycolysis in microglia is “fueling the fire or fighting it”, and protecting neuronal metabolism. Many of the invited speakers work with preclinical models, brain aging or neurodegeneration, with most of the speakers working specifically on studies related to identifying alterations in metabolism that lead to impaired function and strategies for neuroprotection. A key concept is that energy metabolism is not just a permissive factor but is a driver of changes in brain function associated with age-associated disease. Trainee presentations are key aspects of the meeting and bring a new generation of scientists into our community to foster their maturation by having them as speakers and session co-chairs. In addition to talks by early career investigators, at least 20 students/postdocs will be awarded travel stipends based on competitive ranking of abstracts, and the top 8-9 will present short talks. This conference will provide an outstanding venue for cross-disciplinary interactions between basic neuroscientists and clinicians. Formal talks and informal discussions are always highlights of this unique conference series that fosters new collaborations and scientific interactions to address emerging issues.

NIA - National Institute on Aging

Project Summary NIH supported research aims to advance our understanding of biological systems, improve the control of disease, and enhance health. It is well-recognized that connecting investigators with complementary expertise’s in fundamental cell biology, biochemistry, genetics, state of the art imaging with those developing avenues for the treatment of disease are essential to get effective advances. This grant proposal seeks support for the 2026 Gordon Research Conference (GRC) and associated Gordon Research Seminar (GRS) on Lysosomes and Endocytosis, with a central theme of “Endosomes and Lysosomes in Action Across Cells, Tissues and Disease States”. As the field of Lysosomes and endocytosis evolves with increasing research in this aging related topics, the 2026 meeting will place an important emphasis on neurodegenerative disease, specifically Alzheimer Disease and related aging disorders. Exploring at the cellular, molecular and structural levels how defects in lysosomal and endocytic processes contribute to disease onset and progression are essential fundaments for therapeutical intervention. Endosomes and lysosomes are critical components of the endomembrane system, orchestrating essential cellular processes including cargo sorting, degradation, membrane trafficking, and signaling. Their coordinated activity ensures proper cellular homeostasis and adaptability across a wide range of cell types and tissue environments. Emerging evidence highlights their dynamic and context-dependent roles in development, immunity, metabolism, and cell fate determination. Notably, dysregulation of endo-lysosomal pathways is increasingly recognized as a central contributor to the pathogenesis of numerous diseases, including neurodegenerative disorders, cancers, metabolic syndromes, and lysosomal storage diseases. The GRC will bring together internationally recognized experts and emerging scientists to present unpublished data, stimulate discussion, and develop new collaborations. The GRS, held prior to the main conference, will offer a focused environment for trainees and junior researchers to present their work and build professional networks to boost their careers.

NIA - National Institute on Aging

PROJECT SUMMARY The ovary is one of the first organs to age, impacting fertility and endocrine function. The aging ovary is characterized by a loss of egg quantity and quality as well as changes in the microenvironment, including chronic sterile inflammation and fibrosis. “Fibroinflammaging” is a common feature of many aging somatic tissues and is in part driven by accumulation of cellular debris. Interestingly, the ovary has an incredibly dynamic physiology and is under immense pressure to manage cellular debris to maintain tissue homeostasis, which likely explains its accelerated aging. Throughout the reproductive lifespan, the ovary undergoes continuous waves of follicular growth and atresia, cycles of ovulatory rupture, and formation and regression of the corpus luteum (CL), a transient endocrine organ formed post-ovulation. These events require continuous tissue remodeling and result in high cellular debris burden. We have demonstrated that CL regression is dysregulated with age and results in the accumulation of persistent CLs (pCLs) or ovulatory debris. Concomitantly, we identified a unique age- associated macrophage population, multinucleated giant cells (MNGCs), which exhibit pro-inflammatory and degradative phenotypes and stimulate an inflammatory response in follicles and tissue remodeling in the stroma, thus acting as key effectors of fibroinflammaging. Transcriptomically, pCLs are an intermediate between functional CLs and MNGCs and may be a precursor of ovarian MNGC formation. This proposal posits a novel mechanistic framework of ovarian aging mediated by age-related failure to effectively remove ovulatory debris. We will test the hypothesis that age-associated persistent ovulatory debris drives ovarian fibroinflammaging and that enhancing debris clearance mechanisms will improve function and reproductive longevity. In Aim 1, we will define age-related changes in CL regression and the activity of debris clearance mechanisms. Using a CL labeling approach, we will map regression across age and conduct targeted analyses of apoptosis, autophagy, and efferocytosis to investigate how ovarian debris clearance activity is altered. We will also utilize multi-omics approaches to define the content of ovulatory debris. In Aim 2, we will determine how ovulatory debris contributes to MNGC formation and fibroinflammaging. We will leverage mouse models with different degrees of cumulative ovulation to define the relationship between ovulation, debris accumulation, and fibroinflammatory phenotypes. In addition, we will use ex vivo approaches to determine whether CL debris can directly stimulate ovarian MNGC formation. In Aim 3, we will test whether targeted modulation of ovulatory debris impacts ovarian function and healthspan. We will employ a GPNMB-targeted vaccination strategy to deplete pCLs and MNGCs, which exclusively express this marker in the ovary, and assess the effects on reproductive and systemic aging endpoints. Complementary transplantation studies will evaluate the impact of excess pCL burden. This study will establish defective clearance of ovulatory debris as a critical and targetable ovarian aging mechanism.

NIA - National Institute on Aging

SUMMARY This proposal requests funds to support the 54th Annual Meeting of the American Aging Association (AGE) that will take place on June 2-5, 2026, in Provo, UT. The annual AGE meeting is one of the pre-eminent meetings focused on geroscience and brings together scientists at all career stages from around the world as a way to support the mission of AGE to promote biomedical aging studies that target increasing the functional lifespan of humans, to keep the public informed on these activities, to increase knowledge of geroscience among health care professionals, and to support and advance the scientific and professional career development of AGE trainees and scientific members. The 54th Annual AGE Meeting will be held in conjunction with the Nathan Shock Centers of Excellence in the Basic Biology of Aging Symposium (June 2). Since its first conference in 1971, the American Aging Association has been the only scientific society in the United States focused solely on the biology of aging. The annual AGE meeting also closely aligns with the mission of the National Institute on Aging with goals to convene senior and junior scientists in a forum where the latest discoveries in aging research are discussed and debated, to highlight exciting new research in the field, to promote the emergence of new ideas and collaborative activities among participants and to stimulate and advance development of new investigators in aging research. The theme for the AGE 54th annual meeting is “Geroscience from Discovery to Application”. The invited speakers include prominent established scientists, early career investigators, and trainees, all of whom will be selected based on the quality and impact of their science. We have planned 10 noncompeting oral sessions that will be held along with three special lectures and multiple opportunities for network development. Advancing the scientific and professional development of the next generation of geroscientists is a primary goal of the society and we have outlined specific trainee programs to leverage the experience and expertise of senior members of AGE. In addition, we have chosen to have at least one to two speakers in each of the sessions as early-career investigators or trainees selected from submitted abstracts. Two poster sessions are planned that will not compete with oral presentations. Abstracts will be reviewed and scored, and the top 40 poster presenters will be given the opportunity to present their posters in a two-minute oral “poster pitch” during the regular sessions. We seek to have approximately ½ of all session speakers from early career researchers or trainees, and all speakers as recognized experts in the field, or those with growing expertise and high impact trajectory. We request funds to support both invited speakers (early career and trainee) as well as supplement travel grants for outstanding trainees to attend. We expect that the meeting will be held in person with a live-streamed virtual component. AGE has experience with both fully virtual and hybrid meetings. We will adhere to established meeting guidelines, including ensuring that day care opportunities and special needs access are provided.

NIA - National Institute on Aging

SUMMARY Since its inception in 1985, the goals of the Kern Lipid Conference have been to promote lipid science and increase the understanding of diseases involving altered lipid metabolism. The conference strives to provide an open forum for established and young emerging scientists from academia and industry. To this end, the 2026 Kern Lipid Conference will be co-chaired by Drs. Kimberley D. Bruce, Clair Crewe, Robert H Eckel, and Philipp Scherer, representing a range of scientific expertise and career stages. In 2026, the Kern Lipid Conference will be held at the Viceroy Hotel in Snowmass, Colorado (August 10-12th, 2026) with a new timely theme, “Lipids and Lipoproteins in Cardiometabolic and Neurodegenerative Disease”, which responds to the emerging role of lipids and lipoprotein metabolism in age-associated neurodegenerative diseases such as Alzheimer’s disease. Since this meeting is attended by world leaders in metabolism, this conference is the ideal opportunity to bring peripheral metabolic scientists and neuroscientists together. Therefore, the primary goals of the 2026 conference are (1) to provide an interactive environment that leads to novel insights into the shared mechanisms driving age-associated cardiovascular and neurodegenerative disease involving lipids and lipoproteins (2) to engage and inspire young scientists from a range of scientific disciplines to develop their careers studying lipid and lipoprotein biology, cardiometabolic, and neurodegenerative disease pathogenesis. There are 8 scientific sessions in the 2026 scientific program, covering the following topics: (1) Peripheral Lipids and Neurodegenerative Disease (2) Causative Factors in Hyperlipidemia, (3) Lipoproteins in Cardiometabolic and Neurodegenerative disease, (4) Lipid Signaling, (5) Lipids as Immunometabolic Regulators (6), Emerging Technologies in Lipid analysis and Imaging (7) ApoE and Apolipoproteins, and (8) Lipid Droplets and Lipophagy. Idea exchange is maximized by allocating ample time for questions and discussion after oral presentations, shared meals, an evening poster session, and career development roundtables. The Kern Conference has traditionally attracted many early career scientists (~40% of the participants), established scholars in their fields, as well as creative scientists from the industry. Participation of young scientists is strongly promoted with opportunities to present, serve as session chairs, and receive prestigious early-career awards that will facilitate career development: the Roger Davis Investigator Award for Transitional Faculty, the David L Williams Lecture Award, and the Franz Simon Poster Award. Overall, the tranquil setting and meeting format will facilitate interdisciplinary interactions, making it likely that novel insights into disease mechanisms and therapeutic approaches for cardiometabolic and neurodegenerative diseases will emerge from the 2026 Conference. This R13 application is critical to the success of the 2026 Kern Conference because it will enable us to support the attendance and highlight research from more early career scientists.