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.

An expert consensus statement on biomarkers of ageing for use in intervention studies.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

Full-length direct RNA sequencing uncovers stress granule-dependent RNA decay upon cellular stress.

Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5' end adapter ligation, to comprehensively interrogate the human transcriptome at single-molecule and -nucleotide resolution.

The Utility of Long-Read Sequencing in Diagnosing Early Onset Parkinson's Disease.

Objective: Variants in PRKN and PINK1 are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN or PINK1 variant.

Cerebral white matter myelination is associated with longitudinal changes in processing speed across the adult lifespan.

Myelin's role in processing speed is pivotal, as it facilitates efficient neural conduction. Its decline could significantly affect cognitive efficiency during ageing. In this work, myelin content was quantified using our advanced MRI method of myelin water fraction mapping.

LINC02257 regulates malignant phenotypes of colorectal cancer via interacting with miR-1273g-3p and YB1.

Colorectal cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) are involved in the progression of various types of cancer. In this study, we aimed to identify potential causal lncRNAs in CRC through comprehensive multilevel bioinformatics analyses, coupled with functional validation.

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.

Background: Cerebral blood flow normally places a limit on the magnitude of brain vascular permeability (P) that can be measured in vivo. At normal cerebral blood flow, this limit falls at the lower end of lipophilicity for most FDA-approved CNS drugs. In this study, we report on two methods that can be used to overcome this limitation and measure brain vascular permeability values that are up to ~1000 times higher using the in situ brain perfusion technique.

Plant-Based Diets and Their Associations with Physical Performance in the Baltimore Longitudinal Study of Aging.

Background: Plant-based diets are associated with various health benefits; however, their impact on physical performance in aging populations remains unclear.

Objectives: To investigate the associations between adherence to plant-based diets and physical performance, focusing on their potential protective effects against age-related declines in function.

Methods: Data were obtained from men and women aged 40 years or older in the Baltimore Longitudinal Study of Aging (BLSA) (mean ± SD age: 68 ± 13 years at the first dietary visit; n = 1389).

A 2-year calorie restriction intervention reduces glycomic biological age biomarkers.

Background/objective: In a subset of participants from the CALERIE Phase 2 study we evaluated the effects of 2y of ~25% Calorie Restriction (CR) diet on IgG N-glycosylation (GlycAge), plasma and complement C3 N-glycome as markers of aging and inflammaging.

Methods: Plasma samples from 26 participants in the CR group who completed the CALERIE2 trial and were deemed adherent to the intervention (~>10 % CR at 12 mo) were obtained from the NIA AgingResearchBiobank. Glycomic investigations using UPLC or LC-MS analyses were conducted on samples from baseline (BL), mid-intervention (12 mo) and post-intervention (24 mo), and changes resulting from the 2y CR intervention were examined.

Pathways From Socioeconomic Factors to Major Cardiovascular Events Among Postmenopausal Veteran and Nonveteran Women: Findings From the Women's Health Initiative.

Background: Cardiovascular disease (CVD) remains a leading cause of death for women in the United States, with veterans being at potentially higher risk than their nonveteran counterparts due to accelerated aging and distinct biopsychosocial mechanisms. We examined pathways between selected indicators of socioeconomic status (SES) such as education, occupation, household income, and neighborhood SES and major CVD events through lifestyle and health characteristics among veteran and nonveteran postmenopausal women.

Methods And Results: A total of 121 286 study-eligible WHI (Women's Health Initiative) participants (3091 veterans and 118 195 nonveterans) were prospectively followed for an average of 17 years, during which 16 108 major CVD events were documented.

The CALERIE Genomic Data Resource.

Caloric restriction (CR) slows biological aging and prolongs healthy lifespan in model organisms. Findings from the CALERIE randomized, controlled trial of long-term CR in healthy, nonobese humans broadly supports a similar pattern of effects in humans. To expand our understanding of the molecular pathways and biological processes underpinning CR effects in humans, we generated a series of genomic datasets from stored biospecimens collected from n = 218 participants during the trial.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Urolithin A and nicotinamide riboside differentially regulate innate immune defenses and metabolism in human microglial cells.

Introduction: During aging, many cellular processes, such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses, become compromised. Urolithin A (UA) and Nicotinamide Riboside (NR) are two naturally occurring compounds known for their anti-inflammatory and mitochondrial protective properties, yet the effects of these natural substances on microglia cells have not been thoroughly investigated. As both UA and NR are considered safe dietary supplements, it is equally important to understand their function in normal cells and in disease states.

Intentional Strategic Changes in the National Institute on Aging's RCMAR Program: Broadening its Scope and Reach to Strengthen its Impact.

Since 1997, the Resource Centers for Minority Aging Research (RCMAR) program, supported by the Division of Behavioral and Social Research (BSR) at the National Institute on Aging (NIA), has served as BSR's flagship mentoring program for early-career scientists from diverse backgrounds. The program has undergone significant changes over time, adapting to meet institutional and societal needs. This article highlights the motivations behind programmatic shifts in the fifth funding cycle (2018-2023) and the guiding principles for RCMAR VI (2023-present).

'I still remember': Increased categoric autobiographical memories in behavioural variant of frontotemporal dementia.

Autobiographical memory is diminished in patients with behavioural variant of frontotemporal dementia (bvFTD), and research has focused on the hampered ability of patients to retrieve specific memories. In this study, we implemented a methodology seeking to provide a qualitative analysis of autobiographical specificity. We invited patients with bvFTD and control participants to retrieve autobiographical memories and we distinguished between specific, categoric, extended and semantic autobiographical retrieval.

Impact of UPF2 on the levels of CD81 on extracellular vesicles.

Extracellular vesicles (EVs) are involved in cell-to-cell communication. Following uptake, EV cargo molecules, including DNA, RNA, lipids, and proteins, influence gene expression and molecular signaling in recipient cells. Although various studies have identified disease-specific EV molecules, further research into their biogenesis and secretion mechanisms is needed for clinical application.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

The ZFHX3 GGC Repeat Expansion Underlying Spinocerebellar Ataxia Type 4 has a Common Ancestral Founder.

Background: The identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25-year diagnostic conundrum. We used adaptive long-read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat expansion in affected individuals from Utah, Sweden, and Germany, highlighting the current pivotal time for detection of novel repeat expansion disorders.

Different germline variants in the XPA gene are associated with severe, intermediate, or mild neurodegeneration in xeroderma pigmentosum patients.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by pathogenic variants in seven nucleotide excision repair genes (XPA to XPG) and POLH involved in translesion synthesis. XP patients have a >1000-fold increased risk for sunlight-induced skin cancers. Many Japanese XP-A patients have severe neurological symptoms due to a founder variant in intron 3 of the XPA gene.