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IRB No. 21-257-2 (Dr. Breno Diniz, PI): The SenDep Study: Linking Molecular Senescence Changes to Depression and Cognitive Impairment in Late Life

Late-life depression (LLD) is a common mental disorder in the elderly, with prevalence rates ranging from 1 to 5%. Recent evidence suggests that LLD is linked to age-related negative health outcomes, such as cerebrovascular disease, increased risk of Alzheimer's disease, vascular dementia, and of premature mortality. The mechanisms of LLD are complex and involve the dysregulation of different biological pathways. Understanding the interplay between the biological changes in aging and depression can provide insight into the mechanisms by which LLD increases the risk of negative health outcomes. This study proposes to evaluate the association of Senescence-Associated Secretory Phenotype (SASP) Index with different clinical phenotypes of aging (i.e., cognitive impairment) and with cellular senescence phenotype (i.e., leukocyte telomere [LT] attrition) in LLD. Finally, we will evaluate the trajectory of changes in SASP, and its relationship with cognitive performance in these individuals. Our hypotheses are that LLD individuals will show a significantly higher SASP index compared to age- and gender-matched never-depressed control subjects. SASP index will be significantly associated with greater cognitive impairment and telomere attrition in LLD subjects. We further hypothesize that an increasing or persistently higher SASP index trajectory will lead to faster cognitive decline among study participants over two years of follow-up. To our knowledge, this will be the first study to examine the association between circulating molecular senescence markers (SASP), a cellular senescence marker (LT attrition), and neurocognitive and clinical characteristics in LLD. Based on the results of this study, we will also be able to identify novel targets for the development of interventions aiming not only the treatment of depression in the elderly but also aiming the prevention of the negative outcomes related to this condition

IRB No. 22-179J-1 (Dr. George Kuchel, PI): A deep longitudinal analysis of next generation influenza vaccines in older adults

This study is a collaboration between The Jackson Laboratory for Genomic Medicine (JAX) in Farmington, CT and UConn Health in Farmington, CT. All recruitment, enrollment, clinical data, and sample collection will occur at the UConn Center on Aging (COA), at UConn Health in Farmington, CT under the direction of Dr. George Kuchel, Professor of Medicine and Director of the UConn COA. Coded samples collected at Visits 1-17 will be securely transported to the Jackson Laboratory for Genomic Medicine (JAX), located on the UConn Health campus, for processing, storage, sequencing, and analysis. Dr. Duygu Ucar will oversee sample management and sample and data analysis per protocol. In this study, a total of sixty (60) healthy adults aged 65 years and older who have had no history of confirmed COVID-19 and have not received influenza vaccination for the approaching influenza season will be enrolled in the study and vaccinated with influenza vaccines approved by the U.S Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for individuals ≥65 years. All participants receive influenza vaccine during the 2022-23, 2023-24, and 2024-25 influenza seasons. Participants will receive Fluzone® Quadrivalent High-Dose vaccine during the 2022-23 and 2024-25 flu seasons and FLUAD® Quadrivalent during the 2023-24 flu season. Blood samples will be collected from the participants at each of the seventeen study visits over three years. Nasal swab and stool samples will also be collected from participants at 7 time-points across the study period. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this proposed study. By performing comprehensive profiling of their blood antibodies and immune cells over time, we will be able to associate specific age-related immune alterations with vaccine responder or non-responder status, thus allowing us to pinpoint biological pathways that can be targeted to enhance vaccine efficacy and that can also help us to progress towards developing a universal influenza vaccine.

IRB No. 23-089-2 (Dr. Cutter Lindbergh, PI): Computerized Cognitive Remediation of Long COVID Symptoms in Older Adults

Evidence is mounting that a significant minority of patients who develop coronavirus disease 2019 (COVID-19), especially older adults, show lingering neuropsychiatric symptoms including cognitive impairment, brain fog, and depression. These neuropsychiatric symptoms -- which are commonly referred to under the umbrella term "Long COVID" -- are debilitating and may last for months or even years after viral infection. There is a severe lack of evidence-based treatments. The purpose of the present study is to help address this public health crisis by determining whether computerized "brain-training" treatment has potential for improving thinking, mood, and other aspects of day-to-day functioning in older adults with Long COVID. There are two main aims of the present study. The first aim is to simply determine the "feasibility" of using brain-training treatment in older adults with Long COVID. This includes examining whether Long COVID patients are willing to engage in the treatment and whether they find the treatment acceptable and credible. The second aim is to gather preliminary data on whether the brain-training treatment appears to improve memory, thinking, mood, and other aspects of daily functioning in older adults with Long COVID.

IRB No. 23-134-2 (Dr. Julie Robison, PI): UConn Pepper Center (OAIC) Recruitment Volunteer Registry

Objective/Goals: The Research Volunteer Registry (RVR) is a mailing list that is used to invite and share opportunities to participate in future research studies and to community educational events the UConn Pepper Center will host.

IRB No. 23-173-1 (Dr. Roshanak Sharafieh, PI): Biomarker Development to Promote Geroscience-Guided Approaches to Chronic Wound Management in Older Adults

This research is being done to help better understand the role that senescent cells play in human wound healing in older adults. The goals of this pilot project are to provide: 1) junior faculty interested in human subjects research involving older adults with experience in the preparation of an IRB protocol, recruitment of human subjects and frailty assessments 2) provide investigators interested in translational aging research with the opportunity to generate early stage feasibility and preliminary human data that could then be used in future NIH grant applications. This will be accomplished using a cohort of older adults who have a lower extremity wound and studying their healing of the wound tissue compared to that of the healthy tissue over time. In order to achieve the objective, we propose the following aims: In Aim 1, Dr. Sharafieh and her research team will recruit individuals who have developed new early-stage lower extremity wounds within 1-3 weeks of presentation. Baseline research assessments will be completed and working with Drs Alam, Santiago, and/or Kerr, a tissue biopsy will be obtained to look for cellular senescence markers. In Aim 2, all individuals recruited during initial wound presentation (Aim 1) will be followed 5-7 weeks later and again 8-12 weeks after the onset of the wound to repeat clinical wound assessment, repeat wound biopsy. The purpose of this is to identify and quantify similarities and differences in wound biopsies throughout their healing process. The results from this follow up will show what markers are associated with senescence in the wounds when compared to individuals with properly healing wounds.

IRB No. 24-127J-1 (Dr. George Kuchel, PI): Hematopoietic epigenetic memory as a driver of inflammaging

This is a prospective, single-visit study. The UConn Center on Aging will recruit 80 healthy community-dwelling young (20-35 years old, n=40: 20 men, 20 women) and older adults (>65 years old, n=40: 20 men, 20 women). Blood samples (50 mL, single draw) will be collected from these participants and participants will be clinically assessed using Frailty Index, frailty phenotype and blood-borne measures of biological aging. This research is being done to determine how aging affects the rare blood stem cells that give rise to the circulating immune cells.. Scientists may conduct genomic testing of cells in blood in this research. This means that they will be looking at which genes are turned on and which are turned off in immune cells. This study may help contribute to new strategies to rejuvenate the immune system and responses.

IRB No. 24-066-2 (Dr. Iman Al-Naggar, PI): Mito-LUTS: A Pilot Study of the Effect of MitoQ on Lower Urinary Tract Symptoms in Older Women with Metabolic Syndrome

Objectives: The goal of this pilot study is to serve as proof-of-concept that using MitoQ, a supplement with gerotherapeutics properties, to target shared biological pathways between aging, metabolic syndrome and lower urinary tract symptoms (LUTS) represents a much-needed novel direction in alleviating lower urinary tract symptoms. It will also help identify and validate biomarkers described in the literature for LUTS diagnosis and severity and generate data required to design and power future clinical trials. Aims: Aim 1: Elucidate the effect of MitoQ on lower urinary tract symptoms (LUTS) in older women with MetS. We will carry out a double-blinded, placebo controlled randomized pilot and exploratory study to test the effect of MitoQ on LUTS in older women with MetS. Older women (50-75 years) with both LUTS (no UTI, with urgency possibly accompanied by other symptoms such as frequency, urgency or urge incontinence for at least 3 months), and MetS (International Diabetes Federation (IDF) definition) will be randomized 2:1 into a treatment (40mg/day MitoQ, for 16 weeks) and placebo arm (Total number of participants will be 50). Assessments of LUTS using well-validated questionnaires and 3-day voiding diaries will be done at baseline, during, and at the end of the drug administration period. Main outcome will be change in LUTS questionnaire scores from baseline for each individual and between Placebo and MitoQ groups. We hypothesize that treatment with MitoQ will improve LUTS questionnaire scores in females with MetS, whereas the placebo group scores will remain unchanged or worsen Aim 2: Measure the effect of MitoQ on biomarkers and their biomarkers and their correlation with LUTS severity. There are currently no clinically useful biomarkers that are specific for LUTS, and novel biomarkers that can reliably distinguish LUTS are urgently needed. A good biomarker would also help with choice of therapy, predict response, change with an intervention and reflect changes in symptom severity. Aim 2a: Does treatment with MitoQ in females with MetS-related LUTS alter blood and urinary biomarkers of biological hallmarks of aging and LUTS? We will measure biomarkers of inflammation and oxidative stress in blood and urine at baseline and 16 weeks after treatment initiation in our participants. We will also measure urinary proteins and metabolites shown to correlate with overactive bladder syndrome (OAB) and others reported to be urotoxic or uroprotective. Values will be compared to baseline for each subject and means will be compared between groups. We hypothesize that MitoQ will reduce biomarkers of inflammation, oxidative stress, and OAB, while also decreasing urotoxic metabolites and increasing uroprotective metabolites. Aim 2b: Do changes in biomarkers correlate with types of LUTS and their severity? In order to be clinically useful, a biomarker should correlate well with LUTS type and severity. Biomarker levels will be correlated to LUTS questionnaire scores and voiding diary parameters. Because LUTS can have multifactorial etiology, no single biomarker has been useful. We aim to identify a panel of biomarkers for diagnosis, prognosis, tailoring, and tracking interventions. We hypothesize that changes in biomarkers will reflect changes in LUTS and correlate with LUTS severity. Study Design: This will be a randomized, placebo-controlled, double-blinded pilot and exploratory study. Participants in the MitoQ intervention group will receive MitoQ capsules (40 mg/day), whereas placebo control group will receive capsules containing all inactive ingredients prepared by the same manufacturer without the MitoQ, for 16 weeks.

IRB No. 24-125-1 (Dr. Archana Sanjay, PI): Analyzing the impact of aging on skeletal stem and progenitor cells in human bone marrow

This study will examine tissue biospecimens normally discarded from orthopaedic procedures to determine how aging impacts tissue on the cellular level. We plan to collect those discarded biospecimens and transfer them to the Musculoskeletal Institute Research Lab of Dr. Sanjay for preparation and analysis. Using these tissue biospecimens, we will attempt to understand and characterize the effects of aging on a cell's regenerative potential.