Skeletal Muscle mRNA Splicing Variants Association With Four Different Fitness and Energetic Measures in the GESTALT Study.

Background: Physical activity is essential for maintaining muscle mitochondrial function and aerobic capacity. The molecular mechanisms underlying such protective effects are incompletely understood, in part because it is difficult to separate the effects of disease status and physical activity. We explored the association of human skeletal muscle transcriptomic with four measures of energetics and mitochondria oxidative capacity in healthy individuals.

Sex differences in the trajectories of plasma biomarkers, brain atrophy, and cognitive decline relative to amyloid onset.

Introduction: The factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid-positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid-β.

Methods: Linear mixed-effects modeling investigated overall and sex-specific longitudinal trajectories of plasma biomarkers, brain volumes, and cognition relative to the estimated age of amyloid onset in a cohort of 78 amyloid-positive Baltimore Longitudinal Study of Aging (BLSA) participants (n = 45 male; follow-up time: 6.

Decreased SNCA Expression in Whole-Blood RNA Analysis of Parkinson's Disease Adjusting for Lymphocytes.

Blood-based RNA transcriptomics offers a promising avenue for identifying biomarkers of Parkinson's Disease (PD) progression and may provide mechanistic insights into the systemic biological processes underlying its pathogenesis beyond the well-defined neurodegenerative features. Previous studies have indicated an age-dependent increase in neutrophil-enriched gene expression, alongside a reduction in lymphocyte counts, in individuals with PD. These immune cell changes can obscure disease-relevant transcriptomic signals.

Dysregulation of astrocytic Aquaporin-1 in the brains of oldest-old rhesus macaques: the NIA caloric restriction study.

Aquaporin-1 (AQP1) is a highly conserved water-channel protein, found to be expressed by astrocytes in adult humans and non-human primates (NHPs). Upregulation of cortical AQP1 expression occurs with cancer, injury, and neurodegenerative disease, but minimal information is available about the effects of normative aging on AQP1 expression. This study leverages tissues from the oldest-old rhesus macaques, some greater than 40 years of age, from the National Institute on Aging longitudinal study of caloric restriction (CR).

An Insulin Upstream Open Reading Frame (INSU) Is Present in Skeletal Muscle Satellite Cells: Changes with Age.

Insulin resistance, stem cell dysfunction, and muscle fiber dystrophy are all age-related events in skeletal muscle (SKM). However, age-related changes in insulin isoforms and insulin receptors in myogenic progenitor satellite cells have not been studied. Since SKM is an extra-pancreatic tissue that does not express mature insulin, we investigated the levels of insulin receptors (INSRs) and a novel human insulin upstream open reading frame (INSU) at the mRNA, protein, and anatomical levels in Baltimore Longitudinal Study of Aging (BLSA) biopsied SKM samples of 27-89-year-old (yrs) participants.

Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells.

The rate of spontaneous action potentials (APs) generated by sinoatrial node cells (SANC) is regulated by local Ca release (LCR) from the sarcoplasmic reticulum via Ca release channels (ryanodine receptors, RyRs). LCR events propagate and self-organize within the network of RyR clusters (Ca release units, CRUs) via Ca-induced-Ca-release (CICR) that depends on CRU sizes and locations: While larger CRUs generate stronger release signals, the network's topology governs signal diffusion and propagation. This study used super-resolution structured illumination microscopy to image the 3D network of CRUs in rabbit SANC.

Alzheimer's Disease polygenic risk, the plasma proteome, and dementia incidence among UK older adults.

Alzheimer's Disease (AD) is a complex polygenic neurodegenerative disorder. Its genetic risk's relationship with all-cause dementia may be influenced by the plasma proteome. Up to 40,139 UK Biobank participants aged ≥ 50y at baseline assessment (2006-2010) were followed-up for ≤ 15 y for dementia incidence.

Identifying diagnosed major chronic diseases associated with recent housing instability among aging adults: data from the 'All of Us' research program.

Background: Housing instability is a known barrier to healthcare utilization potentially affecting the prevention, diagnosis and treatment of chronic diseases among diverse groups of adults. We examined the intersection of recent housing instability with prevalent cardiovascular disease, diabetes, cancer and psychiatric diagnoses among aging adults.

Methods: Cross-sectional data on 147 465 participants of the 'All of Us' Research Program (6 May 2018-1 July 2022), ≥50 years of age at enrollment, were analyzed.

Comparative lifespan and healthspan of nonhuman primate species common to biomedical research.

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing strict inclusion criteria, primary results are based on 12,269 NHPs that survived to adulthood and died of natural/health-related causes.

Correlates of six-month housing instability among U.S. adults by veteran status: Exploratory study using data from the All of Us Program.

Housing instability (HI) is a social determinant of health affecting adults in the United States (U.S.).

Association between Accelerometer-Measured Irregular Sleep Duration and Longitudinal Changes in Body Mass Index in Older Adults.

Irregular sleep duration may disrupt circadian rhythms and contribute to metabolic, behavioral, and mood changes, potentially increasing the risk for obesity. However, quantitative data on the relationship between sleep duration irregularity and weight change are lacking. In this prospective study, we analyzed data from 10,572 participants (mean age: 63 years) in the UK Biobank who wore accelerometers for a week between 2013-2015 and had two body mass index (BMI; kg/m) measurements on average 2.

Prediction, prognosis and monitoring of neurodegeneration at biobank-scale via machine learning and imaging.

Background: Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD) are the most common neurodegenerative conditions. These central nervous system disorders impact both the structure and function of the brain and may lead to imaging changes that precede symptoms. Patients with ADRD or PD have long asymptomatic phases that exhibit significant heterogeneity.

Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium.

Background: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

Methods: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567).

Neighborhood social cohesion and sleep health among sexual minoritized US adults and intersections with sex/gender, race/ethnicity, and age.

Objectives: Neighborhood social cohesion or living in communities characterized by trust and social ties may mitigate sleep disparities among sexual minoritized vs. heterosexual persons; but its relation to sleep health is understudied among sexual minoritized groups. To investigate associations between perceived neighborhood social cohesion and sleep health among adult US men and women who identified as "lesbian or gay, bisexual, or something else," we used cross-sectional National Health Interview Survey data (2013-2018).

Cross-sectional analysis of speed-up mechanism in normal gait among healthy older adults with and without falls - Results from the Baltimore Longitudinal Study of Aging.

Background: Falls in older adults increase the risk of mobility loss. Proper understanding of gait mechanisms related to falls may provide novel solutions for maintaining mobility in older adults.

Research Question: Identify fall-related gait patterns through analyzing alterations in gait parameters to walk faster than usual pace in older adults.

Cerebellum in neurodegenerative diseases: Advances, challenges, and prospects.

Neurodegenerative diseases (NDs) are a group of neurological disorders characterized by the progressive dysfunction of neurons and glial cells, leading to their structural and functional degradation in the central and/or peripheral nervous system. Historically, research on NDs has primarily focused on the brain, brain stem, or spinal cord associated with disease-related symptoms, often overlooking the role of the cerebellum. However, an increasing body of clinical and biological evidence suggests a significant connection between the cerebellum and NDs.