Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Lifetime risk and projected burden of dementia.

Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.

Loss of HNRNPK During Cell Senescence Linked to Reduced Production of CDC20.

Cellular senescence is a complex biological response to sublethal damage. The RNA-binding protein HNRNPK was previously found to decrease prominently during senescence in human diploid fibroblasts. Here, analysis of the mechanisms leading to reduced HNRNPK abundance revealed that in cells undergoing senescence, mRNA levels declined transcriptionally and full-length HNRNPK protein was progressively lost, while the abundance of a truncated HNRNPK increased.

Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.

Sex-dependent adaptations in heart mitochondria from transgenic mice overexpressing cytochrome b reductase-3.

Cytochrome b reductase 3 (CYB5R3) overexpression upregulates mitochondrial biogenesis, function, and abundance in skeletal muscle and kidneys, and mimics some of the salutary effects of calorie restriction, with the most striking effects being observed in females. We aimed to investigate the mitochondrial adaptations prompted by CYB5R3 overexpression in the heart, an organ surprisingly overlooked in studies focused on this long-lived transgenic model despite the critical role played by CYB5R3 in supporting cardiomyocytes mitochondrial respiration. Given that CYB5R3 effects have been found to be sex-dependent, we focused our research on both males and females.

Previous short-term disuse dictates muscle gene expression and physiological adaptations to subsequent resistance exercise.

Short-term unloading experienced following injury or hospitalisation induces muscle atrophy and weakness. The effects of exercise following unloading have been scarcely investigated. We investigated the functional and molecular adaptations to a resistance training (RT) programme following short-term unloading.

Ca/Calmodulin-Dependent Protein Kinase II (CaMKII) Regulates Basal Cardiac Pacemaker Function: Pros and Cons.

The spontaneous firing of the sinoatrial (SA) node, the physiological pacemaker of the heart, is generated within sinoatrial nodal cells (SANCs) and is regulated by a "coupled-clock" pacemaker system, which integrates a "membrane clock", the ensemble of ion channel currents, and an intracellular "Ca clock", sarcoplasmic reticulum-generated local submembrane Ca releases via ryanodine receptors. The interactions within a "coupled-clock" system are modulated by phosphorylation of surface membrane and sarcoplasmic reticulum proteins. Though the essential role of a high basal cAMP level and PKA-dependent phosphorylation for basal spontaneous SANC firing is well recognized, the role of basal CaMKII-dependent phosphorylation remains uncertain.

Associations of personality traits with actigraphic sleep in middle-aged and older adults.

Although prior studies have examined associations of personality traits with sleep, most have investigated self-reported sleep, been cross-sectional, and focused on younger and middle-aged adults. We investigated associations of personality with actigraphic sleep parameters and changes in sleep in 398 cognitively normal adults aged 40-95 years (M ± SD = 70.1 ± 12.

Effect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.

Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.

HEPATOCYTE GROWTH FACTOR FOR WALKING PERFORMANCE IN PERIPHERAL ARTERY DISEASE.

Introduction: VM202 is a plasmid encoding two isoforms of hepatocyte growth factor (HGF). In preclinical studies, HGF stimulated angiogenesis and muscle regeneration. This preliminary clinical trial tested the hypothesis that VM202 injections in gastrocnemius muscle would improve walking performance in people with mild to moderate and symptomatic lower extremity peripheral artery disease (PAD).

Effects of early, late and self-selected time-restricted eating on visceral adipose tissue and cardiometabolic health in participants with overweight or obesity: a randomized controlled trial.

The optimal eating window for time-restricted eating (TRE) remains unclear, particularly its impact on visceral adipose tissue (VAT), which is associated with cardiometabolic morbidity and mortality. We investigated the effects of three TRE schedules (8 h windows in the early day, late day and participant-chosen times) combined with usual care (UC, based on education about the Mediterranean diet) versus UC alone over 12 weeks in adults with overweight or obesity. The primary outcome was VAT changes measured by magnetic resonance imaging.

Curcumin Mitigates Gut Dysbiosis and Enhances Gut Barrier Function to Alleviate Metabolic Dysfunction in Obese, Aged Mice.

The gut microbiome plays a critical role in maintaining gut and metabolic health, and its composition is often altered by aging and obesity. This study aimed to investigate the protective effects of curcumin on gut dysbiosis, gut barrier integrity, and bile acid homeostasis in aged mice fed a high-fat, high-sugar diet (HFHSD). Eighteen- to twenty-one-month-old male C57BL/6 mice were divided into groups fed a normal chow diet or HFHSD, with or without curcumin supplementation (0.

Has Muscle Power Better Discriminative Capacity Compared To Muscle Strength In Predicting Worsening Disability In Older Adults?

Background: Poor muscle strength is a risk factor for disability; nonetheless its discriminative capacity in identifying people who will become disabled is poor. We evaluated whether muscle power, which also is a risk factor for disability, has better discriminative capacity compared to muscle strength.

Methods: We used data from the population based InCHIANTI study.

Feasibility and Acceptability of Collecting Passive Smartphone Data for Potential Use in Digital Phenotyping Among Family Caregivers and Patients With Advanced Cancer.

Purpose: Modeling passively collected smartphone sensor data (called digital phenotyping) has the potential to detect distress among family caregivers and patients with advanced cancer and could lead to novel clinical models of cancer care. The purpose of this study was to assess the feasibility and acceptability of collecting passive smartphone data from family caregivers and their care recipients with advanced cancer over 24 weeks.

Methods: This was an observational feasibility study.

Long-term impact of Diabetes Prevention Program interventions on walking endurance.

Objectives: Type 2 diabetes (T2D) and prediabetes are associated with poor walking endurance, a marker of physical function. We aimed to examine the long-term effects of metformin or intensive lifestyle intervention in adults at high risk of T2D on their 6-min walk test (6MWT) performance.

Methods: Participants were randomized in the 3-year Diabetes Prevention Program (DPP) to one of the three groups: lifestyle intervention, metformin, or placebo, and were subsequently followed in the DPP Outcomes Study.

Higher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade.

Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k) is associated with less ventricular enlargement and brain aging progression, and less atrophy in specific regions, notably primary sensorimotor cortex, temporal white and gray matter, thalamus, occipital areas, cingulate cortex, and cerebellum white matter.

Peripheral risk factors and their role in biomarker-based screening for dementia in the community.

Introduction: Peripheral risk factors (PRFs) may correlate with dementia plasma biomarkers, potentially reflecting peripheral rather than brain health. This study explores the associations between PRFs and plasma biomarkers glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total-tau, and their role in predicting future dementia.

Methods: Data from the Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2015) included 4353 participants mean age of 76.

Characterization of DNA methylation in PBMCs and donor-matched iPSCs shows methylation is reset during stem cell reprogramming.

DNA methylation is an important epigenetic mechanism that helps define and maintain cellular functions. It is influenced by many factors, including environmental exposures, genotype, cell type, sex, and aging. Since age is the primary risk factor for developing neurodegenerative diseases, it is important to determine if aging-related DNA methylation is retained when cells are reprogrammed to an induced Pluripotent Stem Cell (iPSC) state.

Prioritizing Parkinson's disease risk genes in genome-wide association loci.

Recent advancements in Parkinson's disease (PD) drug development have been significantly driven by genetic research. Importantly, drugs supported by genetic evidence are more likely to be approved. While genome-wide association studies (GWAS) are a powerful tool to nominate genomic regions associated with certain traits or diseases, pinpointing the causal biologically relevant gene is often challenging.

Life's Essential 8 and midlife trajectories in cognition and brain health: The CARDIA study.

Introduction: Poor cardiovascular health (CVH) is linked to Alzheimer's disease and dementia; however, its association with neurocognitive trajectories earlier in life remains underexplored.

Methods: We included 3224 participants with information on CVH at early midlife (mean age 45.0 ± standard deviation 3.

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.