Aging

Background: Some people experience cognitive decline as they age. That is, they lose memory, problem-solving, and other mental abilities. Amyloids are groups of proteins that develop in the brain and increase in number as people age. Researchers want to use imaging scans to track amyloids in people s brains over time. Their goal is to find out if any changes are related to cognitive decline or other medical issues. Objective: To learn how amyloids may affect brain structure and function as people age. Eligibility: People aged 55 years and older who are enrolled in the Baltimore Longitudinal Study of Aging. Design: Participants will have imaging scans and other tests every 1 to 4 years, depending on their age. Those 80 and older will be scanned yearly. These scans will be done during regular BLSA visits. The scans will be positron emission tomography and computed tomography (PET CT). Participants will be given fluid through a tube inserted into a vein in their arm. The fluid is a tracer that will cause the amyloids to light up in the images. Then they will lie on a bed with their head inside a PET CT scanner. They will lie still for about 30 minutes. Participants will have tests to assess their memory and other mental skills. They will answer questions about their mood and daily life. These tests will take about 40 minutes to complete; they may be done in person or by phone. Participants will give a contact number for someone who can answer questions about the participant s daily routine. These questions may be answered in person or by phone. Participants will be in this study for 5 years.

The primary objective of this new line of research is to test whether augmenting sensory information from the legs, using Walkasins sensory neuroprosthesis, can enhance performance of a complex walking task in older adults with foot sensory impairment. The overarching hypothesis is that Walkasins will enhance the automaticity and reduce cognitive demand of walking in older adults with foot sensory impairments, as measured by reduced prefrontal activity, decreased dual-task costs, and lower gait variability.

This is a randomized, double-blind, placebo-controlled, two-arm crossover clinical trial evaluating the effects of nicotinamide mononucleotide (NMN) combined with trimethylglycine (TMG) supplementation, compared to NMN alone. The study will assess safety and efficacy in improving exercise tolerance and modulating biomarkers of aging in healthy older adults. The primary outcome is cycle ergometry constant work rate (CWR) exercise tolerance, measured as time to fatigue. Secondary outcomes include changes in peak oxygen consumption (VO₂peak), critical power, anaerobic work capacity, lactate threshold, and NAD⁺ metabolite levels. The supplements have been used in prior exploratory studies and real-world applications, which have helped inform the design of this current trial.

This study consists of three aims focused on examining the feasibility of adding the Geriatric Resources and Assessment for the Care of Elders (GRACE) model to structured Annual Wellness Visits (AWVs) to improve patient and caregiver outcomes and reduce hospitalizations in older adults with complex health needs. The objectives are to: 1. Co-design a community-centric implementation strategy for the AWVs vs AWVs + GRACE -augmented care (AWV GRACE) study arms 2. Develop a referral pathway and algorithm to optimize enrollment of eligible participants 3. Conduct a pilot clinical trial to assess the feasibility of the AWV GRACE intervention.

Background: When people have a stroke, they often have difficulty moving their arms and hands. Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke can move their arms and hands. But the effects of TMS are minor, and it doesn t work for everyone. Researchers want to study how to time brain stimulation so that the effects are more consistent. Objective: To understand how the brain responds to transcranial magnetic stimulation so that treatments for people with stroke can be improved. Eligibility: Adults ages 18 and older who had a stroke at least 6 months ago Healthy volunteers ages 50 and older Design: Participants will have up to 5 visits. At visit 1, participants will be screened with medical history and physical exam. Participants with stroke will also have TMS and surface electromyography (sEMG). For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple movements during TMS. For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded. At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the loud noise. At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG, small electrodes on the scalp will record brainwaves. Participants will sit still, watch a movie, or do TMS. Participants may be asked to have 2 extra visits to redo procedures.

The goal of this clinical trial is to evaluate the impact of an integrated smart voice platform on quality of life and local healthy aging among community-dwelling older adults in both urban and rural areas. The main questions it aims to answer are: Does the smart voice platform, integrating healthcare, long-term care, and health promotion resources, improve the community life quality of elderly participants? Participants will: Receive access to and training on an existing smart voice platform system that connects healthcare, long-term care, and local cross-domain resources (businesses, NPOs, and NGOs). Complete assessments evaluating their quality of life, digital capability, and healthy aging outcomes.

The frequency and severity of heat waves has increased in the last decades. Older adults (over 65 years) have impaired responses to heat stress making them at increased risk for adverse events. Previous heat waves report that women over 65 experience worse health outcomes than any other age group and age matched men. Aging and reproductive hormones, specifically estrogen, independently alter responses to heat stress. However, the combined effects of low estrogen following menopause and aging on the response to heat stress are unknown. In this study, the investigators will identify the role of estrogen in pre and post menopausal women on thermoregulatory responses to heat stress.

To critically examine biological, clinical, and behavioral modulators of progressive resistance training-associated exercise response heterogeneity in physical function and whole-body metabolism in older adults.

Considerable heterogeneity in the aging population has been observed. The exceptional longevity of individuals reaching 100 years old, so-called centenarians may be an example of life-long healthy aging, or added years may be spent in poor health with decreased physical and cognitive functioning. Current knowledge of the aging experience and the trajectories of physical and cognitive decline across various age groups are not well-understood, yet crucial to prevent spending added years in disease. Hence, the study objective is to develop the metabolic profile associated with aging-related disorders measured as the incidence of impaired functional capacity, cognitive function, and/or well-being.

This is a 16-week randomized controlled trial (RCT) with outcome assessor blinding. The objective is to investigate the effects of resistance training (RT) combined with whole-body neuromuscular electrical stimulation (WB-NMES) and a high-protein diet on body composition, anthropometry, and quality of life. Sample and Group Allocation The sample will comprise 36 older adults (≥ 60 years), physically inactive, and with overweight or obesity (BMI ≥ 25 kg/m²). They will be randomized (stratified by sex) into four groups of 9 participants: RT + NOR: Resistance training + normal-protein diet. RT + PRO: Resistance training + high-protein diet. WB-NMES + RT + NOR: Resistance training with electrical stimulation + normal-protein diet. WB-NMES + RT + PRO: Resistance training with electrical stimulation + high-protein diet. Intervention Protocol Exercise (2x/week, 25 min/session): Seven exercises (2 sets of 1 min execution with 45s of rest). Progressive intensity controlled by the OMNI-RPE Scale. Electrical Stimulation (WB-NMES Groups): Simultaneous use of an electrode suit (85 Hz, 400 µs pulse width, 5s on/5s off duty cycle), with intensity capped at a maximum of 5/10 on the pain/discomfort Visual Analog Scale (VAS). Nutrition (In-person + Remote): High-protein (PRO) groups will focus on an intake of 1.2 to 1.5 g of protein/kg/day. Normal-protein (NOR) groups will receive general healthy eating guidelines, without encouraging an increase in protein intake. Assessments and Outcomes (Conducted at T0 and T16) Body Composition and Anthropometry: Multi-frequency bioelectrical impedance (InBody 570) and circumference measurements following ISAK guidelines. Physical and Functional Performance: Handgrip strength (dynamometry). Muscular endurance (30-second chair stand and arm curl tests). Upper limb power (2 kg medicine ball throw). Aerobic endurance (6-Minute Walk Test). Mobility and fall risk (Timed Up and Go - TUG). Questionnaires and Scales: Self-reported functional disability (WHODAS 2.0). Basic psychological needs satisfaction (BPNES). Motivational regulation in exercise (BREQ-3). Quality of life specific for older adults (WHOQOL-OLD). Adherence: Minimum attendance goal of 75% for the sessions. Statistical Analysis The analysis will follow the intention-to-treat (ITT) principle. Data will be analyzed using Linear Mixed Models for Repeated Measures (fixed factors: Group and Time), followed by Tukey's post-hoc test, adopting a significance level of $p \< 0.05$.

This is a Phase I, open-label, non-randomized clinical trial to evaluate the safety and preliminary efficacy of adipose-derived mesenchymal stem cell secretome capsules (VinVital) in patients with frailty syndrome. A total of 20 participants aged 60 to 75 will receive oral VinVital for 3 months, with an additional 3-month follow-up period (total 6 months). The primary objective is to assess safety based on the frequency and severity of adverse events (AEs) and serious adverse events (SAEs) according to CTCAE v5.0.

People with HIV who drink alcohol are at increased risk for accelerated aging biology, including increased immune senescence. This randomized, double-blind, crossover clinical trial evaluates two generally recognized as safe (GRAS) microbiota-targeted interventions on immune senescence biomarkers.

The aging of the U.S. population, combined with health care workforce shortages and insufficient access to effective fall prevention and exercise programs, has contributed to a high burden of fall-related injuries in older adults, especially in those with Mild Cognitive Impairment (MCI), a precursor of Alzheimer's dementia (AD) and related dementias (ADRD). There is an urgent need for scalable, evidence-based interventions that can be delivered efficiently in the home setting. This study aims to evaluate the efficacy and impact of a comprehensive digital fall prevention program (Digital STEADI) delivered through a technology platform with two conversational agents that leverage generative artificial intelligence (gen-AI) with human oversight to increase program access, enhance adherence to clinical fall prevention protocols and best practices, and reduce fall risk among community-dwelling older adults.

Older adults with breast cancer frequently present with frailty, decreased functional reserve, and increased risk of postoperative complications. Prehabilitation programs have emerged as a promising strategy to improve physical function and clinical outcomes; however, evidence in geriatric oncology remains limited, particularly regarding the role of biological markers in predicting response to such interventions. This study aims to evaluate the effectiveness of a multicomponent prehabilitation program in older adults with breast cancer, focusing on functional status, clinical outcomes, and quality of life. In addition, the study seeks to characterize biological markers associated with frailty and treatment response, with the goal of identifying potential predictors of benefit from prehabilitation. Participants will undergo a structured prehabilitation intervention including physical exercise, nutritional optimization, and comprehensive geriatric assessment. Clinical, functional, and biomarker data will be collected longitudinally. The results of this study may contribute to improving personalized care strategies in geriatric oncology and to identifying patients who are most likely to benefit from prehabilitation programs.

The Westlake Longevity Cohort (We-Longevity) is a prospective cohort study among centenarians, nonagenarians and senior citizens living in Zhejiang Province, China. The primary aim of this cohort is to characterize the multi-omics molecular characteristics of healthy longevity and their dynamic trajectories. The second aim is to culture the gut microbiota of these elderly people through culturomics. The third aim of We-Longevity is to investigate the association of dietary and lifestyle with the multi-omics molecular characteristics of healthy longevity, and to facilitate the development of personalized nutritional/lifestyle recommendation for the public.

This study investigates the influence of sex hormones and exercise on age-related neuromuscular decline in females. Specifically, the research aims to evaluate how hormonal variations impact both age-associated neuromuscular decline and the subsequent adaptations to exercise and resistance training. Age-related declines in neuromuscular function are especially pronounced in females, potentially due to the sharp drop in estradiol after menopause. This project will compare postmenopausal females who have not taken hormonal therapy (HT) to age-matched females taking HT.

Much of human interaction is based on trust. Aging has been associated with deficits in trust-related decision making, likely further exacerbated in age-associated neurodegenerative disease (Alzheimer's disease/AD), possibly underlying the dramatically growing public health problem of elder fraud. Optimal trust-related decision making and avoiding exploitation require the ability to learn about the trustworthiness of social partners across multiple interactions, but the role that learning plays in determining age deficits in trust decisions is currently unknown. Aim: Probe the malleability of the underlying neurocircuitry of trust-learning deficits in aging. This study will utilize real-time fMRI neurofeedback to train older adults in brain activity up-regulation toward enhanced trust-related learning in aging and confirm critical mechanisms of experience-dependent social decisions in aging. Grant R01AG072658 Aim 3: Test the malleability of trust-learning neurocircuitry toward optimized trust-related decision making in aging.

Older adults living with a spinal cord injury (SCI) experience an increased burden of secondary health conditions than, coupled with age-related complications, may negatively affect physical and mental health, as well as health-related quality of life (HRQoL). Insufficient physical activity (PA) participation, sedentary behavior, and inadequate nutrition may further contribute to cardiometabolic risk, functional decline, and reduced well-being in this population. Although exercise interventions have demonstrated beneficial effects on cardiorespiratory fitness, muscular strength, mental health, and HRQoL among people with SCI, existing evidence has primarily been established among younger and middle-aged adults. Nutrition is also increasingly recognized as an important component of health management following SCI; however, evidence from nutrition interventions among adults with SCI remains limited. Consequently, we have developed an intervention that includes both exercise and nutrition education for older adults with SCI, and the present pilot randomized controlled trial (RCT) will evaluate its feasibility, fidelity, acceptability, and usability. Participants will be randomized 1:1 to either a 16-week intervention or to a waitlist control group. The intervention integrates an individualized exercise prescription based on the International SCI Exercise Guidelines (Martin Ginis et al., 2018), SCI-specific nutrition education (Sneij et al., 2022), and SCI-specific, theory-informed behavioral counseling (Hoekstra et al., 2023). The behavioral component incorporates strategies intended to support participants' capability, opportunity, and motivation to engage in exercise and healthy eating behaviors. Participants assigned to the waitlist control group will complete a 16-week waiting period before receiving the same intervention. The primary aim of this pilot trial is to determine whether to proceed to a full-scale RCT. We have identified the following a priori criteria for success: i) recruitment of n=24 participants within 12 months, ii) retention ≥90%; and iii) adherence to both exercise and nutrition education sessions ≥90%. Furthermore, we will determine scientific feasibility (i.e., data collection and outcome feasibility) and resource and management feasibility, including fidelity monitoring, time, and resources. Finally, we will explore participants' experiences, perspectives, and preferences regarding barriers and facilitators to the intervention, as well as exercise professionals', nutrition educators', and behavioral coaches' opinions on procedures and potential issues, to inform the design of a future hybrid type-II effectiveness-implementation pragmatic RCT. This pilot RCT will provide feasibility, fidelity, acceptability, and usability metrics that will inform the decision to proceed to a full-scale trial or whether modifications are needed.

Through the implementation of this three-year project, investigators expect to find a safe and effective exercise prescription for patients with oral cancer after surgery. The findings will encourage and promise and add further support to the concept that exercise prescription is worth implementation as part of care for the patients with head and neck cancer.

This study aims to evaluate the prevalence of diastasis recti abdominis (DRA) in the geriatric population and assess the effectiveness of a targeted exercise program on inter-recti distance (IRD) and linea alba stability. Diastasis recti abdominis is a common condition characterized by the separation of the rectus abdominis muscles, which can affect trunk stability, posture, and pelvic floor function. While heavily researched in postpartum women, data regarding DRA in older adults remains limited. In the first observational phase, 500 participants aged 60 and older will undergo ultrasonographic (USG) measurement of the inter-recti distance (2 cm above and 2 cm below the umbilicus) and an assessment of linea alba stability during active movements (cervical flexion, leg raise, and trunk extension). Abdominal circumference will also be measured. Risk factors, functional status, physical activity, urinary incontinence, and low back pain will be evaluated using standardized questionnaires (IPAQ, ICIQ-UI SF, Revised Oswestry Low Back Pain Disability Index) and a custom survey. Participants diagnosed with DRA (IRD 2 cm and/or linea alba instability) will be invited to join the second, interventional phase. They will be randomly allocated to either an experimental exercise group or a control group. The exercise group will perform a structured 8-to-10-week exercise program, while the control group receives no intervention. Follow-up assessments (USG, stability testing, and questionnaires) will be conducted for both groups after the 8-10 week period to compare outcomes.

Two hallmarks of both healthy aging and age-related disease are 1) memory and navigational deficits, particularly in orienting towards goal locations and planning how to navigate to them, and 2) increased susceptibility to stress and altered regulation of the stress response. However, there are marked individual differences in these age-related changes. The investigators' proposal will help characterize factors that contribute to this variability. Participants will be pseudorandomly assigned to stress-manipulated or control groups. The investigators will give both groups a novel immersive navigation task, validated by the PI in healthy young adults. This paradigm gives participants the opportunity to either (a) flexibly draw on spatial memory in order to plan efficient routes to goal locations, or (b) fall back on inefficient, but cognitively less-demanding, stimulus-response associations (i.e., habits). Using neuroimaging and behavioral measures, the investigators' protocol will test whether experimentally-induced stress leads individuals to bring fewer details about future locations to mind when route planning, and whether such restricted prospective thought ultimately biases participants towards relatively inflexible, habitual actions.

There are over one million Veterans who identify as lesbian, gay, bisexual, (LGB) or a related identity. Older LGB Veterans face unique hurdles as they age, including stress, anxiety, heart disease, cancer, decreased ability to perform activities of daily living, delayed care, and increased likelihood of entering a nursing home. Sparse social networks and limited access to aging resources are common for LGB Veterans and contribute to adverse outcomes. The proposed study will partner with older Veterans to adapt and test a virtual structured group that promotes healthy aging, self-acceptance, and connection to health-related resources. This study aims to improve Veterans' health and well-being through increased resilience, positive healthcare engagement, and access to resources that support older Veterans' needs. There are currently no other VA programs designed to address the unmet needs of older LGB Veterans. By learning more about how to serve subgroups of Veterans more effectively, this study will also improve outcomes for all older Veterans and their care partners.

The purpose of this study is to test whether young-donor fecal microbiome transplantation (FMT) and a fermented, plant-rich high-fiber, microbiome rejuvenating diet (MRD) reduce inflammatory and biological aging markers. Participants (≥40 years) will be randomized (1:1:1:1) for 8 weeks with 4-week follow-up to: (A) diet alone, (B) FMT alone, (C) diet + FMT, or (D) Placebo FMT. We will use rigorously screened young and healthy FMT donors and encapsulated delivery. Outcomes include change from baseline to end of dietary intervention (week 8) in markers of aging and inflammation. Secondary outcomes include defining microbiome engraftment/diversity/function, key metabolites, diet adherence, and quality-of-life.

A growing body of research has highlighted the importance of frontal regions, at both the functional and structural levels, in age-related declines in attentional and cognitive processing. However, the underlying neurobiological pathophysiological changes in the brain that contribute to these declines are still largely unclear. The objective of this proposal is to investigate neural mechanisms of age-related attentional distractibility, focusing on the neural circuit initiated from the locus coeruleus (LC). In the current proposal, the investigators will test the hypothesis that the neural disconnectivity of LC with the salience network (SN) drives failures of ignoring distractors in older adults. The investigators will examine how LC-SN connectivity is associated with selective attention performance, and how improved LC-SN connectivity through a cognitive training program may lead to improved attentional performance.

This observational study will evaluate whether sperm cryopreservation can help preserve sperm quality and molecular characteristics that may be affected by increasing paternal age. Men aged 18 years and older will provide a semen sample and a blood sample for laboratory analysis. Each semen sample will be divided into fresh, slow-frozen, and vitrified aliquots. The study will compare sperm quality (as assessed by computer-assisted sperm analysis), DNA methylation profiles, DNA fragmentation, sperm telomere length before and after cryopreservation. The effects of age on these parameters will also be assessed. The impact of age on seminal plasma extracellular vesicle composition and blood cell telomere length will also be analysed. The goal is to determine whether sperm cryopreservation may represent a strategy for preserving sperm characteristics associated with younger paternal age.