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Synaptic Vesicle Glycoprotein 2A Suppresses Amyloidogenesis Beyond Its Synaptic Role: A Novel Mechanism Disrupting BACE1 Binding and Altering APP Localization
Synaptic vesicle glycoprotein 2A (SV2A), a transmembrane protein widely localized to synaptic vesicles, serves as a key indicator of synaptic loss in Alzheimer's disease (AD). In this study, adeno-associated virus (AAV) was injected by brain stereotactic injection technique to construct SV2A-overexpressing APP/PS1 mice, then the effects of SV2A on amyloid precursor protein (APP) degradation and its molecular mechanism were further explored in vivo or in vitro. Our results demonstrated that SV2A...
Impact of Transposable Elements on DNA Double-Strand Break Repair and Genomic Stability
Transposable elements (TEs) are indispensable components of eukaryotic genomes, mechanistically linked to carcinogenesis, aging and other degenerative diseases. The ability of TEs to self-propagate and cause deletions, inversions or insertions within the genome poses a real threat to the fidelity of genomic integrity. This review discusses the fundamental properties of TEs, with a focus on cellular interactions associated with mechanisms involved in recombination, replication, and DNA repair....
The Secretome of Human Trophoblast Stem Cells Attenuates Senescence-Associated Traits
Senescent cells display indefinite growth arrest and a pro-inflammatory, senescence-associated secretory phenotype (SASP). As the accumulation of senescent cells in tissues with age plays detrimental roles in age-related pathologies, there is much interest in finding therapeutic strategies to eliminate them or suppress the SASP. In this study, we investigated the impact of the secretome and extracellular vesicles (EVs) derived from human trophoblast stem cells (hTSCs) on senescent human...
Astronauts as a Human Aging Model: Epigenetic Age Responses to Space Exposure
Spaceflight exposes astronauts to a combination of environmental stressors such as microgravity, ionizing radiation, circadian disruption, and social isolation that induce phenotypes of aging. However, whether these exposures accelerate biological aging remains unclear. In this exploratory study, we assessed 32 DNA methylation-based biological age metrics in 4 astronauts during the Axiom-2 mission at pre-flight, in-flight (day 4 and 7), and post-flight (return days 1 and 7). On average,...
NMNAT1 Activates Autophagy to Delay D-Galactose-Induced Aging in Cochlear Hair Cells
With an aging population, the incidence of age-related hearing loss (ARHL) continues to increase. Aging cells exhibit reduced nicotinamide adenine dinucleotide (NAD^(+)) levels and impaired autophagy; however, the mechanisms underlying these processes remain largely unclear. In our study, we assessed the role of nicotinamide nucleotide adenylate transferase 1 (NMNAT1) in cochlear hair cell aging using D-galactose (D-gal)-induced aging HEI-OC1 cells and cochlear explants. We observed a...
Decreased PTGES2 Farnesylation in Granulosa Cells Compromises PGE2-Dependent Cumulus Expansion and Oocyte Maturation During Ovarian Aging
With the increasing trend of delayed childbearing, the decline in oocyte quality associated with advanced maternal age has emerged as a pressing concern. However, the mechanism remains unclear, and effective strategies for improvement are currently lacking. Previously, we reported that the downregulation of the mevalonate pathway in aged granulosa cells (GCs) contributed to meiotic defects in oocytes, which may implicate farnesyl pyrophosphate-mediated protein farnesylation. Nevertheless, the...
Effects of Dual-Task and Single-Task Interventions on Physical and Cognitive Function in Older Adults: A Scoping Review
CONCLUSION: This review provides a comprehensive comparison of dual-task and single-task interventions, highlighting the superior efficacy of dual-task training in improving both cognitive and physical outcomes. While single-task interventions offer benefits, they lack the comprehensive improvements observed in dual-task training. Future research should explore long-term outcomes, refine intervention protocols, and assess the applicability of combined approaches to maximize benefits for aging...
Scientists spot never-before-seen shock wave around dead star
Observation challenges understanding of how dead stars interact with their environments
A multi-target therapeutic framework for Alzheimer's disease: an integrative mechanistic review
CONCLUSIONS: AD management requires a systems-oriented therapeutic architecture in which interventions are selected based on mechanistic dominance, biomarker stage, and potential synergy. We outline a multi-target strategy integrating amyloid/tau modulation, neuroimmune regulation, metabolic-vascular stabilization, and synaptic support. Future work should prioritize biomarker-guided stratification, treatment sequencing, and prevention-oriented combination designs.
Fasting as Medicine: Mitochondrial and Endothelial Rejuvenation in Vascular Aging
Aging drives a progressive decline in vascular health, undermining endothelial function, neurovascular coupling (NVC), and blood-brain barrier (BBB) integrity, three processes essential for maintaining cerebral perfusion and cognitive resilience. Central to these age-related deficits is mitochondrial dysfunction, which disrupts redox balance, bioenergetics, and nutrient-sensing pathways within vascular cells, thereby promoting oxidative stress, impaired mitophagy, mitochondrial fragmentation,...
Hevin Promotes Aging-Related Cardiac Dysfunction via Facilitating Cardiac Inflammation in Male Mice
As individuals age, there is a gradual increase in the levels of inflammation in the body, with macrophages, essential immune cell types, assuming a critical role in modulating inflammatory responses and eliminating senescent cells. Prolonged inflammatory reactions can result in tissue damage, the advancement of diseases, and the acceleration of aging processes. Hevin (also known as SPARCL1, secreted protein acidic and rich in cysteine-like protein 1) is involved in regulating inflammatory...
Metabolites released from apoptotic cells in central nervous system orchestrates the pathological process of Alzheimer disease through improving autophagy
Apoptosis, a programmed cell death process activated in Alzheimer disease (AD), is not limited to neurons but extends to all cell types within the central nervous system (CNS). However, how apoptotic cells mediate their impact on surrounding cells and contribute to the pathological progression of AD remains largely unclear. Here, we report that in 5×FAD mice, cells surrounding amyloid-β (Aβ) plaques undergo apoptosis, which occurs concurrently with elevated macroautophagy/autophagy. The...
Insights into Mechanism of Ionic Liquids for Protein Stability: Future Implications for Neurodegeneration Treatment
Neurodegenerative diseases are characterized by a gradual loss of neurons, cellular dysfunction, loss of intricate synaptic networks and brain damage, which are going to be the second leading cause of death in future. These proteinopathies are marked by abnormal amyloid fibril deposition, aberrant aggregation of misfolded proteins via polymerization, where protein aggregates serve as key pathological hallmarks in Alzheimer's, Parkinson's, and multiple system atrophy disorders. These toxic...
The Role of the Gut Microbiome in the Complex Network of Frailty Syndrome and Associated Comorbidities in Aging
The gut microbiota changes throughout life, potentially influencing health and triggering physiological disorders. Frailty syndrome (FS) is an age-related condition that reduces quality of life and increases hospitalization and mortality risks, making early detection and prevention essential in older populations. This study analyzed 16S rRNA gene and metagenomics sequencing of fecal samples from 203 older adults (FS: n = 64, non-FS (NFS): n = 139) to assess the role of gut microbiota in FS and...
Disproportionate increase of extreme obesity among older adults: an exploratory analysis from the English longitudinal study of ageing
CONCLUSIONS: Extreme obesity is rising disproportionately, including among older adults, and requires urgent recognition as a distinct public health challenge. Healthcare systems must adapt to the complex needs of this population, including appropriate medical infrastructure, specialized care pathways, and enhanced clinical guidelines. Ongoing surveillance and tailored interventions are essential to address this growing burden.
Low-grade mucosal inflammation in aged senescence-accelerated mouse-prone 8 mice blunts epithelial barrier recovery after dextran sodium sulphate-induced chronic colitis
The gastrointestinal (GI) barrier maintains gut homeostasis by regulating nutrient absorption and preventing the entry of harmful agents. While its disruption has been linked to chronic disease, stress and dietary lifestyle, the role of aging in intestinal permeability remains subject of debate. Understanding how aging and age-associated inflammation affect barrier integrity is crucial for promoting GI health in the elderly. In this study, we used the Senescence-Accelerated Mouse-Prone 8 (SAMP8)...
Connected Care for Older Adults: A Pilot Intervention Engaging Community Health Workers to Advance Age-Friendly Care in Rural Oregon
CONCLUSIONS: Connected Care for Older Adults incorporates CHWs in primary care settings to deliver age-friendly care to rural, underserved adults 55 and older. Early findings and feedback from participating patients, caregivers, providers, and CHWs suggest that this is a promising approach to delivering age-friendly care.
The "Reducing Inflammation for Greater Health Trial (RIGHT)" Study-Concept, Rationale, and Design
The Reducing Inflammation for Greater Health Trial's (RIGHT) study is a single-center, randomized, double-blind, placebo-controlled trial designed to test whether clazkizumab, an interleukin-6 (IL-6) inhibitor, can improve or slow decline in physical, cognitive, and vascular function in older adults, when compared to a placebo. The trial will enroll participants meeting the following inclusion criteria: (1) ≥ 70 years of age, (2) with low to moderate physical function, defined as self-reported...
Investigating dual-task biomarkers of subjective cognitive decline using functional near-infrared spectroscopy
Older adults with subjective cognitive decline (SCD) may be at a greater risk of cognitive impairment than older adults without SCD (i.e., non-SCD). This study examined dual-task changes in cerebral oxygenation and performance to determine whether these changes may be used as a biomarker in older adults with SCD. Older adults with (n = 24) and without SCD (n = 18) completed neuropsychological assessments and finger tapping and working memory dual-tasks. Cognitive and motor performance were...
Insights into Mechanism of Ionic Liquids for Protein Stability: Future Implications for Neurodegeneration Treatment
Neurodegenerative diseases are characterized by a gradual loss of neurons, cellular dysfunction, loss of intricate synaptic networks and brain damage, which are going to be the second leading cause of death in future. These proteinopathies are marked by abnormal amyloid fibril deposition, aberrant aggregation of misfolded proteins via polymerization, where protein aggregates serve as key pathological hallmarks in Alzheimer's, Parkinson's, and multiple system atrophy disorders. These toxic...