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Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons
In aging cells and animal models of premature aging, heterochromatin loss coincides with transcriptional disruption including the activation of normally silenced endogenous retroviruses (ERVs). Here we show that loss of heterochromatin maintenance and de-repression of ERVs result in a chronic inflammatory environment characterized by neurodegeneration and cognitive decline in mice. We identify distinct roles for HP1 proteins to ERV silencing where HP1γ is necessary and sufficient for H4K20me3...
Erratum for the Research Article "Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer's disease" by L. Xia et al
No abstract
Epigenetic dysregulation of transposable elements in cognitive impairment and Alzheimer's disease
Aging and cognitive impairment increase the risk for Alzheimer's disease (AD), and growing evidence suggests that transposable elements (TEs) in the genome play a role in aging and AD. The mechanisms of TE dysregulation in this context are unclear, but one possibility is that epigenetic changes, including DNA hypomethylation and/or reduced chromatin structure, underlie age- and AD-related TE activity. Therefore, the purpose of the present study was to generate a resource for studying TE...
Association between weight-adjusted waist index and cardiometabolic multimorbidity in older adults: Findings from the English Longitudinal Study of Ageing
The weight-adjusted waist index (WWI) is a novel anthropometric measure designed to better reflect central obesity than traditional indices such as body mass index and waist circumference (WC). This study examined the prospective association between WWI and cardiometabolic multimorbidity (CMM) and evaluated its predictive utility. We included 3,348 participants (mean age 63 years; 45.1% male) from the English Longitudinal Study of Ageing who were free from hypertension, coronary heart disease,...
The National Dementia Workforce Study: Methods for Surveying Community Clinicians Who Provide Care to People With Dementia
People with dementia have complex medical, functional, and social needs and experience highly variable care quality and outcomes across the U.S. health care system. Community-based physicians, nurse practitioners, and physician assistants serve critical roles in diagnosing and managing dementia, yet little is known about this workforce and factors contributing to variability in care. The National Dementia Workforce Study (NDWS), sponsored by the National Institute on Aging, is conducting large...
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Association of playing cards/mahjong with all-cause mortality in older adults: a cohort study
CONCLUSION: Older adults who regularly play cards/mahjong have a lower risk of all-cause mortality, especially in the oldest groups. These leisure activities may promote longevity, but further research is needed to understand why.
Reconstructed cell-type-specific rhythms in human brain link Alzheimer's pathology, circadian stress, and ribosomal disruption
Alzheimer's disease (AD) disrupts behavioral circadian rhythms, but its effects on molecular rhythms in the human brain are poorly understood. Using single-nucleus RNA sequencing (snRNA-seq) from post-mortem cortical samples, we informatically estimated the relative circadian phases of 409 persons with and without AD dementia, reconstructing circadian expression profiles across cell types. Although core clock rhythms were preserved in AD, many cell-type-specific circadian outputs were disrupted....
Strategies to rescue mitochondria in Parkinson's disease: The significance of mitochondrial transfer
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal degeneration and pathological α-synuclein accumulation. Mitochondrial dysfunction is a central feature in PD pathogenesis, contributing to impaired bioenergetics, oxidative stress, neuroinflammation, and defective organelle communication. This review synthesizes the current understanding of mitochondrial quality control mechanisms, including fission, fusion, mitophagy, and biogenesis, and their...
Strengthening Africa's brain health and economic resilience
Africa stands at a decisive moment in which urgent action is essential to safeguard its brain health and economic stability. While Africa's population remains predominantly young, it is expanding and aging rapidly. This demographic shift is projected to drive a sharp rise in neurodegenerative diseases, including Alzheimer's, with profound health and economic costs-but brain health research, policy, funding and care across the continent remain critically underdeveloped. In this Perspective, we...
Composite transposons with bivalent histone marks function as RNA-dependent enhancers in cell fate regulation
Discrete genomic units can recombine into composite transposons that transcribe and transpose as single units, but their regulation and function are not fully understood. We report that composite transposons harbor bivalent histone marks, with activating and repressive marks in distinct regions. Genome-wide CRISPR-Cas9 screening, using a reporter driven by the hominid-specific composite transposon SVA (SINE [short interspersed nuclear element]-VNTR [variable number of tandem repeats]-Alu) in...
Mitigating ion flux vortex enables reversible zinc electrodeposition
Metal anodes hold considerable promise for high-energy-density batteries but are fundamentally limited by electrochemical irreversibility caused by uneven metal deposition and dendrite formation, which compromise battery lifespan and safety. The chaotic ion flow (or ion flux vortex) near the electrode surface, driving these instabilities, has remained elusive due to limitations in conventional techniques such as scanning electron and atomic force microscopies, which are invasive and incapable of...