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Science, Volume 386, Issue 6725, November 2024.

Science, Volume 386, Issue 6725, November 2024.

Plethora of research has shed light on the critical role of synaptic dysfunction in various neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Synapses, the fundamental units for neural communication in the brain, are highly vulnerable to pathological conditions and are central to the progression of neurological diseases. The presynaptic terminal, a key component of synapses...

Neuroinflammation is closely related to the pathogenesis of Alzheimer's disease (AD). One of its prominent cellular components, microglia, is a potent coordinator of neuroinflammation in interplay with the characteristic AD pathological alterations including Aβ, tau, and neuronal defects, which constitute the AD-unique extracellular microenvironment. Mounting evidence implicates Triggering Receptors Expressed on Myeloid Cells 2 (TREM2) in the center of microglial activation, a vital event in the...

Exon skipping technologies enable exclusion of targeted exons from mature mRNA transcripts, which have broad applications in medicine and biotechnology. Existing techniques including antisense oligonucleotides, targetable nucleases, and base editors, while effective for specific applications, remain hindered by transient effects, genotoxicity, and inconsistent exon skipping. To overcome these limitations, here we develop SPLICER, a toolbox of next-generation base editors containing near-PAMless...

The ISR is a cellular signaling pathway that responds to various physiological changes and types of stimulation. The mitochondrial integrated stress response (ISR^(mt)) is a stress response specific to mitochondria which is initiated by eIF2α phosphorylation and is responsive to mitochondrial stressors. The ISR^(mt) triggers diverse metabolic responses reliant on activating transcription factor 4 (ATF4). The preliminary phases of ISR^(mt) can provoke an adaptive stress response that antagonizes...

Coronary heart disease (CHD) and cognitive impairment frequently co-occur in aging populations, yet the molecular mechanisms linking these conditions remain unclear. This study aims to elucidate the roles of key aging-related genes (ARGs), specifically FKBP5 and DDIT3, in the pathophysiology of CHD and cognitive impairment, and to evaluate the therapeutic potential of stellate ganglion block (SGB). Using single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data, we...

Precipitation hardening has been recently validated as a new mechanism for domain wall pinning and mechanical loss reduction in piezoelectrics. While anisometric precipitates have high pinning strengths, there is limited knowledge about the electrical anisotropy of the precipitation-hardened piezoceramics. In the present work, we successfully orient the precipitates in Li(0.18)Na(0.82)NbO(3) piezoceramics by applying a uniaxial stress during the aging and studied its electrical anisotropy....

Polycystic ovary syndrome (PCOS) is a heterogeneous familial disorder affecting up to one in five women. The aetiology remains unclear, but available evidence suggests it is a polygenic disorder with epigenetic, developmental, and environmental components. The diagnostic criteria for PCOS are based on reproductive features, and the syndrome is categorized into several phenotypes that can vary by race and ethnicity. Insulin resistance and metabolic dysfunction have a crucial role in the...

CONCLUSION: Meta-analysis of cross-sectional studies and cohort studies showed that depression in older adults was associated with the development of MCR, and depression increased the risk of MCR in older adults.

INTRODUCTION: Certain situations and contexts during early years of life and childhood can have a significant impact on the health of older individuals. Studies have demonstrated that adversities such as poverty, neglect, abuse, and exposure to chronic stress conditions during the early years of life are associated with a range of health problems in adulthood.

Alzheimer's disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss. In an AD-related mouse model expressing APOE4, XY sex chromosomes heightened...

To elucidate aging-associated cellular population dynamics, we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissues across different life stages, sexes, and genotypes. This comprehensive dataset reveals more than 3,000 unique cellular states and over 200 aging-associated cell populations. Our panoramic analysis uncovered organ-, lineage-, and sex-specific shifts of cellular dynamics during lifespan progression. Moreover, we identify both...

Alzheimer's disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss. In an AD-related mouse model expressing APOE4, XY sex chromosomes heightened...

A list of this decade's most prominent names in ageing research would undoubtedly include many women who have led the field in recent years. While the field, and science in general, still have far to go in achieving gender parity in opportunities and recognition, we can celebrate the progress made to date. However, the longer 'history of the field' that many of us present in our classrooms, conference halls and writings often tends to be dominated by men. Although numerous men have made...

Policy measures designed to address elder abuse, neglect, and exploitation date back to decades, including the Older Americans Act of 1965. Over the years, various legislative actions have aimed to address elder mistreatment, culminating in the Elder Justice Act of 2010. Despite these efforts, policy changes lag behind need, and government funding appropriation is woefully inadequate. On November 29, 2023, the National Collaboratory to Address Elder Mistreatment convened 76 experts from...

CONCLUSIONS: In this preliminary study, Age Self Care facilitated behavior change, including minor home modifications, fall risk reduction, and engagement in social networks, all of which support aging in place.

The telomerase RNA component (Terc) constitutes a non-coding RNA critical for telomerase function, commonly associated with aging and pivotal in immunomodulation during inflammation. Our study unveils heightened susceptibility to pneumonia caused by Staphylococcus aureus (S. aureus) in Terc knockout (Terc^(ko/ko)) mice compared to both young and old infected counterparts. The exacerbated infection in Terc^(ko/ko) mice correlates with heightened inflammation, manifested by elevated interleukin-1β...

Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behaviour associations^(1,2). Several recent studies have shown that thousands of study participants are required for good replicability of BWAS^(1-3). Here we performed analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional MRI studies from the Lifespan Brain Chart Consortium⁴ (77,695 total scans) to demonstrate that optimizing study design is critical for increasing...

Age-related macular degeneration (AMD) is a major cause of vision loss in older adults. AMD is caused by degeneration in the macula of the retina. The retina is the highest oxygen consuming tissue in our body and is prone to oxidative damage. DNA damage is one hallmark of aging implicated in loss of organ function. Genome instability has been associated with several disorders that result in premature vision loss. We hypothesized that endogenous DNA damage plays a causal role in age-related...