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. 2026 Aug 28;48(5):6409–6420. doi: 10.1007/s11357-026-02498-z

The Arlington study of healthy aging: a multidisciplinary community cohort study of functional decline with age

Delaney L Davis 1, Rajvi Shah 1, Logan Pixler 1, Dang M Mai 1, Juliana Santos 1, Camille Chandler 1, Kendall White 1, Jennifer Nguyen 1, Ario S Moradi 1, Javed Choudhari 1, Carrie Arena-Marshall 1,2, Chase Johnson 2, Ledia Kamel 1, Yue Liao 1,3, Tracy L Greer 3,5, Crystal Cooper 3,5, Hunter Ball 3,5, Noelle L Fields 3,6, Xinlei Wang 7, Bethany L Sussman 8, Matthew T Borzage 8,9,10, Paul J Fadel 1,3, Michael D Nelson 1,2,3,4,11,✉
PMCID: PMC13601427  PMID: 42663798

Abstract

The planet is experiencing an unprecedented growth in its human population aged 65 years and older, underscoring the urgent need for comprehensive aging-centered biobehavioral data to guide public health interventions. The Arlington Study of Healthy Aging (ASHA) is a multidisciplinary community cohort study designed to investigate the biological, psychological, and social mechanisms underlying age-related functional decline. Here, we present the study’s rationale, design, and methodological framework. Utilizing a comprehensive, multi-modal assessment strategy—including whole-body MRI, vascular function testing, venous blood biomarkers, cognitive and physical function evaluations, DEXA scans, and continuous remote monitoring of activity, sleep, blood pressure, and glucose—the study captures both quantitative and qualitative dimensions of aging across multiple organ systems (brain, heart, muscle, liver, adipose tissue). A central aim is to identify modifiable risk factors and protective mechanisms that influence aging trajectories. Through interdisciplinary collaboration, ASHA seeks to generate actionable insights to enhance longevity, independence, and quality of life among older adults. NCT 06857877, 2024-09-24.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1007/s11357-026-02498-z.

Keywords: Healthy aging, Older adults, Multi-modal assessment, Community cohort study, Biobehavioral aging, Functional decline, Whole-body MRI, Cognitive and physical function, Remote health monitoring, Longevity and quality of life

Background

The U.S. now has more older adults than ever—nearly 60 million people aged 65 and above—and this population is projected to surge by another 42% by 2050, when more than 23% of Americans will be over 65 years of age [1, 2]. Age is associated with an increased risk of chronic disease, which contributes to functional decline and reduced overall quality of life [3]. For many older adults, these concerns are compounded by cognitive decline, including Alzheimer’s disease and related forms of dementia. Promotion of healthy aging and development of strategies to mitigate age-associated impact on disease therefore represents a major national social and economic challenge.

To address these concerns, we have convened a multidisciplinary team of experts in biomedical imaging, integrative physiology, biomechanics/exercise science, neuroscience, behavioral science, social work, public health, and biostatistics, to initiate the Arlington Study of Healthy Aging (ASHA). This single-site, multi-ethnic community cohort study will support hypothesis-driven cross-disciplinary research on the mechanisms causing biological and functional decline with age. Here, we summarize the rationale, design and methods of ASHA.

Methods and study design

The Arlington Study of Healthy Aging (ASHA, NCT 06857877) is a comprehensive, single-site, multi-ethnic community cohort study conducted at the University of Texas at Arlington. Its design integrates multiple modalities and disciplines—including magnetic resonance imaging (MRI), integrative physiology, exercise science, neuroscience, and remote monitoring—to investigate the biological, psychological, and social mechanisms underlying age-related functional decline. Participants, aged 50–85 years, undergo extensive evaluation across two in-person visits, each lasting 5–8 h. These include full-body MRIs, cognitive and physical function tests, vascular health evaluations, medical history questionnaires, and blood sampling. The study also incorporates wearable technology to monitor sleep, physical activity, blood pressure, and glucose levels. ASHA aims to explore how factors such as ethnicity, sex, lifestyle, environment, and socioeconomic status influence aging, with the ultimate goal of identifying protective factors and interventions that promote healthy aging and reduce disease burden in older adults.

Human subjects protection

The study was approved by the Institutional Review Board at the University of Texas at Arlington (Protocol Number: 2024-0111), in accordance with the Declaration of Helsinki. All participants were informed about the purpose of the study, assured of confidentiality, and provided written consent prior to participation. Participation was voluntary, and respondents could withdraw at any time without consequence.

Study population

The target population consists of 600 adult residents of Tarrant County, Texas, strategically selected to encompass the racial, ethnic, and sex diversity of the United States. The sample will be intentionally structured to ensure robust representation of historically marginalized racial and ethnic populations, with equal distribution across four major racial/ethnic groups—Non-Hispanic Black, Non-Hispanic White, Hispanic or Latino, and Asian—and balanced representation of males and females within each group. By focusing exclusively on Tarrant County, one of the largest and most demographically diverse counties in the United States, the study benefits from a rich mix of urban and rural populations, varied socioeconomic backgrounds, and cultural perspectives. This localized yet diverse recruitment strategy strengthens the study’s ability to explore how environmental, lifestyle, and demographic factors influence aging, while maintaining geographic consistency that enhances data comparability and community relevance, and ensuring methodological rigor by ensuring study procedures are conducted using the same instruments and by the same personnel.

Exclusion criteria include active treatment for cancer; advanced chronic disease such as heart failure, renal failure on dialysis, Parkinson’s disease, or dementia; visual or auditory impairments that preclude neuropsychological testing, non-ambulatory status (i.e., less than 10 m without mobility aid), shortness of breath while performing normal activities of daily living, body mass index > 45 kg/m2, severe gait disorder due to musculoskeletal disease or neurological motor deficit, daily consumption of more than two alcoholic beverages; or estimated life expectancy < 4 years.

The target enrollment of 600 participants was selected to provide a sufficiently large and diverse cohort for comprehensive multidimensional phenotyping across the adult aging spectrum while remaining feasible given the intensive assessment protocol. Because ASHA is designed as a cohort resource to support multiple current and future research questions rather than a single hypothesis-driven study, the sample size was based on balancing scientific value, participant burden, and operational feasibility. This cohort size is expected to provide adequate variability across demographic, physiological, cognitive, and behavioral domains, supporting future investigations of healthy aging and the development of novel aging biomarkers.

Participant recruitment began in November 2024 and is expected to continue for approximately 4 years. Based on projected enrollment rates, recruitment of the target cohort is anticipated to be completed by late 2028. Ongoing recruitment efforts will focus on achieving broad representation across the targeted age range and demographic groups while maintaining the comprehensive phenotyping procedures central to the ASHA study design.

Informed consent and questionnaires

Informed consent and questionnaires, including detailed medical history, are collected through Vibrent Health, a secure, HIPAA-compliant online clinical research platform (Fig. 1) [4]. This digital approach streamlines participant onboarding and data collection, allowing individuals to complete forms remotely at their convenience while ensuring data integrity and privacy. Medical history includes medications, surgeries, physical activity, smoking, alcohol consumption, menstruation history, fall history, level of education, marital status, and zip code. A complete list of the questionnaires is detailed in Supplemental Table 1.

Fig. 1.

Fig. 1

Informed consent and questionnaires, including detailed medical history, are collected through Vibrent Health, a secure, HIPAA-compliant online clinical research platform

Anthropometrics

Height and body weight are measured using an electronic weight scale and stadiometer (Professional 500KL, Health-O-Meter, McCook, IL). Hip and waist circumference are measured with a standard tape measure, according to published guidelines [5].

Whole-body MRI

Comprehensive whole-body MRI is performed in the UT Arlington Clinical Imaging Research Center using a 3 T Siemens MAGNETOM Vida MRI Scanner, operated by a licensed radiologic technologist. Breaks are provided between imaging each organ system (brain, heart, skeletal muscle, and body composition) to maximize participant comfort. A detailed overview of the imaging protocol is provided in the Supplemental Material, illustrated in Fig. 2.

Fig. 2.

Fig. 2

Comprehensive whole-body MRI for cross-disciplinary, multi-organ evaluation. The protocol is illustrated clockwise, beginning at the top right corner with the brain MRI protocol, which includes structural and functional imaging sequences. Moving clockwise, the next section depicts aortic distensibility and vascular stiffness assessment, followed by whole-body composition imaging using a stack of DIXON images extending from the lower head to the toes. Continuing, the figure highlights the muscle MRI approach, then transitions to liver MRI techniques for fat and iron quantification and concludes with cardiac MRI for functional and structural evaluation

The brain MRI protocol integrates a comprehensive suite of structural and functional imaging techniques to provide a multidimensional assessment of cerebral health and neural activity. Structural imaging sequences include T1-weighted magnetization prepared rapid gradient echo (MPRAGE) for high-resolution anatomical detail, T2-weighted fluid attenuated inversion recovery (FLAIR) for detecting white matter lesions and other pathologies, and diffusion tensor imaging (DTI) to evaluate white matter integrity and connectivity. Functional and physiological assessments are conducted using whole-brain arterial spin labeling (ASL) at rest to measure cerebral blood flow, resting-state blood oxygen level dependent (BOLD) functional MRI (fMRI) with concurrent PETCO2 recording to assess intrinsic functional networks, and advanced task-based functional (BOLD fMRI) paradigms to assess cerebrovascular health and brain physiology. These BOLD-MRI paradigms include

  1. Cerebrovascular reactivity (BOLD-CVR): Resting state and breath modulation BOLD fMRI with simultaneous end-tidal CO2 recording, to evaluate cerebral vascular reactivity [6, 7].

  2. Task-based BOLD fMRI, to evaluate cerebral activation related to language, motor control, and executive function, using the NordicNeuroLab stimulus suite:
    1. Visual sentence completion
    2. Picture naming
    3. Motor task (thumb-index finger tapping)
    4. Audible sentence completion

Together, this protocol offers a robust and integrated approach to studying brain structure, function, and vascular physiology across a range of cognitive and clinical domains. A more detailed description of the brain MRI protocol, along with the primary analysis, is included in the Supplemental Material.

The body composition MRI protocol utilizes a whole-body stack of DIXON images, acquired from head to toe, to enable quantification of skeletal muscle size, composition, and total and regional fat mass [8, 9]. This technique separates water and fat signals, allowing for detailed mapping of lean tissue and adipose distribution across anatomical regions. In addition to the whole-body scan, a quantitative 6-point multi-echo DIXON sequence is performed to assess hepatic fat content and liver iron concentration, providing critical insights into metabolic health and risk for conditions such as non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload. Together, these imaging sequences offer a comprehensive, non-invasive evaluation of body composition and organ-specific metabolic status, supporting research in obesity, sarcopenia, and cardiometabolic disease. A more detailed description of the body composition MRI protocol, along with the primary analysis, is included in the Supplemental Material.

The skeletal muscle MRI protocol provides a comprehensive evaluation of muscle structure, composition, and tissue characteristics across the entire thigh. High-resolution T2-weighted imaging is used to assess anatomical integrity and detect structural abnormalities. Quantitative T1 and T2 mapping, and novel fat separated T1 mapping, enable precise tissue characterization, thus offering insights into muscle quality and potential pathological changes. DIXON imaging is employed to calculate fat fraction, allowing for the assessment of intramuscular adipose infiltration—a key marker of muscle degeneration and metabolic dysfunction. Additionally, T2* mapping is included to evaluate tissue oxygenation and iron content, further enhancing the physiological profiling of skeletal muscle. This multi-parametric approach supports advanced research in aging, sarcopenia, metabolic disease, and exercise physiology by providing a rich dataset for understanding muscle health and function. A more detailed description of the skeletal muscle MRI protocol, along with the primary analysis, is included in the Supplemental Material.

The cardiac MRI protocol is designed to provide a detailed and multidimensional assessment of cardiac structure, function, tissue composition, and vascular dynamics. Multiplanar cine imaging is used to evaluate cardiac morphology and ventricular function throughout the cardiac cycle. Phase contrast imaging at the level of the mitral valve leaflets enables quantification of mitral inflow velocities, providing key insights into diastolic function. To assess myocardial mechanics, multiplanar tissue tagging is employed to measure tissue deformation and strain. Quantitative T1 and T2 mapping allows for tissue characterization, identifying fibrosis, edema, or other pathological changes. Diffusion tenor imaging provides a detailed, non-invasive picture heart muscle fiber architecture and microstructural integrity [10]. High-resolution cine imaging of the aorta is performed to calculate aortic distensibility [11], while phase contrast imaging of the proximal ascending and distal descending aorta enables calculation of aortic pulse wave velocity (aPWV), a marker of vascular stiffness [12]. Advanced flow dynamics are captured using 4D flow MRI of the aorta, providing comprehensive visualization of blood flow patterns [13]. Finally, oxygen-sensitive cardiac MRI is used to assess coronary endothelial function and reactivity, offering a non-invasive measure of vascular health and myocardial oxygenation [14, 15]. Together, this protocol delivers a robust and integrative evaluation of cardiovascular physiology, ideal for research in aging, cardiometabolic disease, and vascular health. A more detailed description of the cardiac MRI protocol, along with the primary analysis, is included in the Supplemental Material.

Although the MRI component of ASHA is extensive, participant burden has been carefully considered through scheduling flexibility, participant education, regular communication during imaging sessions, and accommodations when needed. Recruitment and data collection efforts to date have demonstrated strong feasibility, with most participants successfully completing the full imaging protocol and only a small number requiring modifications or accommodations. Ongoing monitoring of participant experience and completion rates will continue to inform protocol optimization while maintaining the depth of phenotyping that is central to the study objectives.

Vascular, cognitive, and physical function testing and venous blood draw

Comprehensive evaluation of vascular function is performed using a multi-modal approach (Fig. 3), with participants fasted for at least 6 h. First, arterial blood pressure is measured in three positions—sitting, standing, and supine—using an automated blood pressure monitor (71WX-B Connex Spot Monitor; Welch Allyn Connex, Skaneateles Falls, NY), allowing for assessment of postural blood pressure regulation [16]. Screening for peripheral artery disease (PAD) is conducted using the SmartDop XT system (Koven Technology, Inc. St. Louis, MO), which provides automated measurements of both ankle-brachial index (ABI) and toe-brachial index (TBI), offering insight into lower extremity arterial health. Central arterial function and arterial stiffness are assessed using the SphygmoCor system (AtCor Medical, Naperville, IL, USA), via pulse wave analysis and pulse wave velocity, respectively [17]. Beat-to-beat blood pressure is measured from a small finger-pressure cuff placed around the middle or index finger using photoplethysmography (Finometer PRO, Finapres Medical Systems, Arnhem, The Netherlands) positioned at heart level. A minimum of 10 min of continuous data was acquired, per published protocols [18]. To evaluate endothelial function and microvascular reactivity, brachial artery flow-mediated dilation (FMD) and reactive hyperemia were measured using Doppler ultrasound (Vivid-i, GE Healthcare, Little Chalfont, UK) and rapid cuff inflation on the upper arm (AG101 air source and E20 rapid cuff inflator, D.E. Hokanson, Inc, Bellevue, WA, USA), distal to the ultrasound probe, according to standard guidelines [19]. Additionally, near-infrared diffuse correlation spectroscopy (MetaOx, ISS Inc.) was applied over the flexor digitorum profundus (forearm) to assess tissue oxygenation kinetics and microvascular reactivity, complementing measures of macrovascular perfusion and informing the interpretation of reactive hyperemia [20, 21]. A more detailed description of the vascular function protocol, along with the primary analysis, is included in the Supplemental Material.

Fig. 3.

Fig. 3

Comprehensive multi-modal vascular assessment. Panel A illustrates blood pressure measurements performed in three positions—sitting, standing, and supine. Panel B depicts peripheral artery disease (PAD) screening, including ankle-brachial index and toe-brachial index assessment. Panel C presents the methodology for pulse wave velocity (PWV) and pulse wave analysis (PWA) to characterize arterial stiffness and central hemodynamics. Panel D illustrates the macrovascular and microvascular function assessment, combining Duplex ultrasound of the brachial artery (representative image shown) with near-infrared diffuse correlation spectroscopy (NIR DCS) over the flexor digitorum profundus. Representative data include brachial artery velocity profiles, DCS-derived blood flow index (BFI), and near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation at baseline, during five minutes of arterial occlusion, and throughout the reperfusion period

Following vascular testing, participants undergo a venous blood draw (~80 mL). Approximately 25 mL of the sample is sent directly to LabCorp for clinical laboratory testing (as detailed in Supplemental Table 4). The remaining blood is processed for storage in our biorepository: whole blood is collected in PAXgene tubes for future genetic and transcriptomic analysis, and plasma and serum are aliquoted for long-term storage at −80 °C. This approach ensures both immediate clinical insight and the preservation of biological material for future mechanistic and biomarker studies.

After the blood draw, participants are offered a light snack (e.g., cereal bar, crackers, juice box, water) to restore energy before completing a battery of cognitive assessments. These include the Montreal Cognitive Assessment (MoCA) for global cognitive screening [22], the NIH Toolbox Cognition Battery and Odor Identification Test for domain-specific and global cognitive evaluation [23], and a prospective memory test that assesses the ability to remember to complete a future intended task based on the presence of external cues (details provided in Supplemental Material). Collectively, this battery provides a broad assessment of cognitive domains including executive function, attention, processing speed, language, episodic memory, and working memory using measures that have demonstrated ability to assess age-related cognitive changes.

Physical function testing follows (Fig. 4), beginning with the Short Physical Performance Battery (SPPB) to evaluate lower extremity strength and mobility [24]. Grip strength is measured using a handgrip dynamometer (Model J00105, JAMAR, ASP Global, Austell, GA), according to standardized approaches [25]. Participants then remove their shoes for measurements of foot length and width (Brannock Device Co., Syracuse, NY), along with their leg length measured from the pelvis to the ankle. Gait speed is then assessed using a ZenoMat walkway (ZenoMetrics, Peekskill, NY), under both normal and cognitively loaded conditions, including counting backwards from 100 by 1 s, naming animals, and counting backwards by 7 s [26]. The visit concludes with a 6-minute walk test to assess endurance and functional capacity, followed by a whole-body dual-energy X-ray absorptiometry (DEXA) scan to quantify lean mass, fat mass, and bone density (Lunar Prodigy Advance, GE Healthcare, Little Chalfont, UK). A detailed description of the physical function protocol, along with the primary analysis, is included in the Supplemental Material.

Fig. 4.

Fig. 4

Comprehensive physical function evaluation. Panel A illustrates the Short Physical Performance Battery (SPPB), which includes tests of balance, sit-to-stand performance, and 4-meter walk speed. Panel B depicts the grip strength assessment using a calibrated dynamometer. Panel C presents the 6-minute walk test (6MWT) for submaximal aerobic capacity and endurance. Panel D describes the dual-task performance protocol, where participants walk at their preferred pace on a Zeno Walkway (Protokinetics). The initial trial involves walking without any additional task, followed by three separate cognitive tasks performed while walking: (1) counting backward from 100 by 1 s, (2) naming animals, and (3) counting backward from 100 by 7s

Remote monitoring

Participants undergo a 7-day continuous monitoring protocol to assess daily physical activity, sleep patterns, cardiovascular dynamics, and glucose regulation (Fig. 5). Daily step count and sleep metrics are tracked using a Fitbit wearable device (Inspire 3, Fitbit, USA), which provides data on movement, activity intensities, sleep duration, and sleep stages. Continuous blood pressure monitoring is performed using the Hilo cuffless bracelet (formerly Aktiia), a validated wearable device that captures blood pressure fluctuations throughout the day and night, offering insights into autonomic regulation and cardiovascular variability. In parallel, participants wear a Libre FreeStyle continuous glucose monitor (CGM), which records interstitial glucose levels every 15 min, enabling the detection of glycemic variability, postprandial responses, and nocturnal glucose trends. A detailed description of the remote monitoring protocol, along with the primary analysis plan, is included in the Supplemental Material.

Fig. 5.

Fig. 5

Remote monitoring. Continuous glucose monitoring performed using the Freestyle Libre system for interstitial glucose tracking. Continuous blood pressure monitoring with the Hilo device, enabling ambulatory blood pressure assessment using a wrist-worn bracelet. Activity and sleep monitoring performed using a wrist-won FitBit wearable device, providing data on physical activity patterns, step count, and sleep metrics

Incidental findings

Incidental findings identified during study procedures are managed according to established institutional and imaging-center protocols. MRI examinations are reviewed in accordance with the imaging center’s standard operating procedures, including evaluation by the Medical Director. Incidental findings are communicated to the Principal Investigator, who facilitates notification of the participant and recommends appropriate medical follow-up. For other study assessments, clinically relevant incidental findings are reviewed by the Principal Investigator and designated study staff and communicated to participants with recommendations to discuss the findings with their primary care provider or other appropriate healthcare professional. The study does not provide clinical diagnosis or treatment, and participants are encouraged to seek follow-up care through their usual healthcare providers.

Data analysis plan

Because ASHA is designed as a cohort resource to support a broad range of current and future research questions, a detailed statistical analysis plan is beyond the scope of this study design paper. Future analyses will employ appropriate multivariable statistical approaches tailored to specific hypotheses, including methods for handling missing data and correction for multiple comparisons when applicable. The rich multi-modal dataset will also support integrative analyses across imaging, vascular, cognitive, physical function, behavioral, and biological domains. As the cohort matures, advanced analytical approaches, including machine learning and systems biology methods, may be applied to identify complex relationships, novel biomarkers, and determinants of healthy aging. Detailed analysis plans and power considerations will be reported in future hypothesis-driven publications.

Data sharing plan

The ASHA study is committed to promoting scientific collaboration and maximizing the impact of the data collected. Following completion of primary study objectives and in accordance with participant consent, institutional policies, and applicable ethical and regulatory requirements, de-identified study data may be made available to qualified investigators through a controlled-access data-sharing process. Requests for data access will be subject to review and approval by the ASHA study leadership and relevant institutional oversight bodies to ensure the protection of participant privacy and confidentiality.

Discussion

The Arlington Study of Healthy Aging (ASHA) represents a comprehensive, multidisciplinary approach to understanding the biological, psychological and social mechanisms underlying age-related functional decline in a diverse, community-based population. By integrating advanced imaging, vascular assessments, cognitive and physical function testing, and continuous real-world monitoring, ASHA is uniquely positioned to generate high-resolution data across multiple domains of aging. This design reflects a growing recognition that aging is not a singular process but rather a complex interplay of systems—cardiovascular, metabolic, musculoskeletal, neurological, and behavioral—that evolve over time and interact with environmental and lifestyle factors.

One of the key strengths of ASHA is its emphasis on integrative physiology, particularly in the domains of cardiometabolic health, vascular function, and skeletal muscle integrity. The inclusion of advanced MRI protocols—such as multi-parametric cardiac imaging, whole-body and liver DIXON scans, and skeletal muscle mapping—provides novel insight into tissue-level changes that precede clinical disease. These imaging modalities are complemented by vascular assessments that span macrovascular and microvascular function, including central blood pressure, arterial stiffness, endothelial function, reactive hyperemia. Together, these tools allow for a nuanced understanding of vascular aging and its relationship to systemic health.

The study’s design also prioritizes functional outcomes, recognizing that cognitive and physical decline are among the most impactful consequences of aging. By incorporating validated tools such as the NIH Toolbox, MoCA, and Short Physical Performance Battery, alongside dual-task gait assessments and the 6-minute walk test, ASHA captures both baseline function and early indicators of decline. The inclusion of continuous monitoring technologies—Fitbit for activity and sleep, Hilo for blood pressure, and FreeStyle Libre for glucose—adds ecological validity and enables tracking of health behaviors and physiological rhythms in real-world settings.

Beyond the assessment of chronological age and functional status, the comprehensive phenotyping framework of ASHA provides a foundation for evaluating biological aging across multiple physiological systems. The integration of vascular function, neuroimaging, cognitive performance, physical function, wearable-derived behavioral measures, and molecular biomarkers may enable the development and validation of biological age metrics, including frailty indices, imaging-derived aging biomarkers, epigenetic clocks, and composite physiological aging scores. Such approaches may provide greater insight into interindividual variability in aging trajectories and help identify mechanisms that contribute to resilience, accelerated aging, and healthy longevity. These multidimensional measures of biological aging are indeed expected to become an important focus of future analyses.

Importantly, ASHA is grounded in community engagement and health equity, with recruitment strategies designed to reflect the demographic diversity of North Texas. What distinguishes ASHA, however, is its uniquely integrative scientific approach, with coordinated multi-organ and multidisciplinary evaluation across numerous fields. By examining organ systems in concert rather than isolation, ASHA generates a more complete understanding of health trajectories and disease mechanisms, especially for conditions that span or interact across physiological systems. This level of integration will allow our investigative teams to uncover patterns that traditional single-organ or single-discipline studies miss.

The ASHA cohort also provides a valuable platform for future translational research in aging. The integration of advanced imaging, vascular physiology, cognitive assessments, physical function measures, wearable technologies, and biospecimen collection creates opportunities for the discovery and validation of novel biomarkers of aging and age-related disease. These data may help identify biological pathways associated with resilience and functional decline, inform the development of targeted interventions, and support the evaluation of emerging geroscience-guided therapeutics. Furthermore, the deeply phenotyped nature of the cohort facilitates participant stratification and recruitment for future clinical trials designed to test interventions aimed at preserving function, delaying disease onset, and promoting healthy longevity.

A notable strength of ASHA is the implementation of a highly standardized and comprehensive phenotyping protocol within a single research center, which promotes consistency in data acquisition, participant assessment, biospecimen processing, and quality assurance procedures. However, the single-site design may limit the generalizability of study findings to populations with different demographic, socioeconomic, geographic, and healthcare backgrounds. Additionally, regional factors unique to the study catchment area may influence observed associations and aging trajectories. While the cohort is designed to include a diverse population of older adults, replication of findings in larger multi-site studies will be important to establish broader external validity. Future expansion of the cohort and collaborative efforts with other aging studies may further enhance the generalizability and translational impact of ASHA findings.

Taken together, the Arlington Study of Healthy Aging offers a model for comprehensive aging research that bridges basic science, clinical application, and community relevance. Its integrative design and rich data collection strategy will enable novel insights into the mechanisms of aging and inform strategies to preserve function, independence, and quality of life across the lifespan.

Supplementary Information

Below is the link to the electronic supplementary material.

ESM1 (422.1KB, docx)

(DOCX 422 KB)

Acknowledgements

We sincerely thank all participants for their invaluable time, commitment, and contribution to this study.

Abbreviations

ASHA

Arlington Study of Healthy Aging

MRI

Magnetic resonance imaging

DEXA

Duel-energy X-ray absorbency

U.S.

United States

HIPAA

Health Insurance Portability and Accountability Act

MPRAGE

Magnetization-prepared rapid acquisition gradient echo

FLAIR

Fluid-attenuated inversion recovery

DTI

Diffusion tensor imaging

ASL

Arterial spin labelling

fMRI

Functional magnetic resonance imaging

PETCO2

End-tidal partial pressure of carbon dioxide

BOLD

Blood oxygen level dependent

CVR

Cerebral vascular reactivity

DIXON

MRI method used to separate fat and water signals.

NAFLD

Non-alcoholic fat liver disease

aPWV

Aortic pulse wave velocity

FMD

Flow mediated dilation

MoCA

Montreal cognitive assessment

NIH

National Institutes of Health

SPPB

Short Physical Performance Battery

CGM

Continuous glucose monitor

Funding

The study is currently internally supported by the College of Nursing and Health Innovation at the University of Texas at Arlington, as well as through generous support from Ms. Abbe Patton.

Declarations

Declaration of generative AI and AI-assisted technologies in the manuscript preparation process

During the preparation of this work, the authors used Microsoft Co-Pilot for drafting text, improving clarity and organization, refining grammar and style, and generating summaries. The authors reviewed and edited the output as needed and take full responsibility for the content of the published article.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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