Aging & Longevity
p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice
Cellular senescence is characterized by irreversible cell-cycle exit, a pro-inflammatory secretory phenotype, macromolecular damage, and deregulated metabolism. Senescent cells are highly associated with age-related diseases. We previously demonstrated that targeted elimination of senescent cells prevents neurodegenerative disease in tau (MAPT^(P301S);PS19) mutant mice. Here, we show that genetic ablation of the senescence mediator p16^(Ink4a) is sufficient to attenuate senescence signatures in...
Distinct systemic impacts of Aβ42 and Tau revealed by whole-organism snRNA-seq
Both neuronal and peripheral tissues become disrupted in Alzheimer's disease (AD). However, a comprehensive understanding of how AD impacts different tissues across the whole organism is lacking. Using Drosophila, we generated an AD Fly Cell Atlas (AD-FCA) based on whole-organism single-nucleus transcriptomes of 219 cell types from flies expressing AD-associated proteins, either human amyloid-β 42 peptide (Aβ42) or Tau, in neurons. We found that Aβ42 primarily affects the nervous system,...
A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase
An in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease aging as a key risk factor for cognitive decline. Herein, we present a spatio-temporal brain atlas (15 different regions) of microRNA expression across the mouse lifespan (7 time points) and two aging interventions. MicroRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and mediate aging speed. We first...
Cation-driven phase transition and anion-enhanced kinetics for high energy efficiency zinc-interhalide complex batteries
Aqueous Zn-halogen batteries, valued for high safety, large capacity, and low cost, suffer from the polyhalide shuttle effect and chaotic zinc electrodeposition, reducing energy efficiency and lifespan. Here we show a cation-driven positive electrode phase transition to suppress the shuttle effect and achieve uniform zinc electrodeposition, along with an anion kinetic enhancement strategy to improve energy efficiency and lifespan. Taking tetramethylammonium halide (TMAX, X = F, Cl, Br) as a...
A serial mediation model of physical exercise and loneliness: the role of frailty and depression
CONCLUSIONS: This study demonstrated a negative correlation between physical exercise and loneliness among older adults, with frailty and depression serving as significant mediators in this relationship. The findings suggest that physical exercise may alleviate loneliness in older adults by enhancing physiological function and fostering psychosocial empowermen.
Sex differences in middle-aged and old Wistar rats in response to long-term sulforaphane treatment for prevention of neuroinflammation, cognitive decline and brain senescence
The nervous system (NS) experiences morphological and functional changes during the aging process, where low-grade chronic inflammation, oxidative stress and senescence are key regulators. Sulforaphane (SFN) is an isothiocyanate that activates redox response and inhibits the inflammatory process, which could modify the pro-inflammatory components of senescent cells secretory phenotype (SASP). Here we aimed to determine if SFN long-term treatment was able to prevent age-associated damage in the...
The age-dependent neuroglial interaction with peripheral immune cells in coronavirus-induced neuroinflammation with a special emphasis on COVID-19
Neurodegenerative diseases are chronic progressive disorders that impair memory, cognition, and motor functions, leading to conditions such as dementia, muscle weakness, and speech difficulties. Aging disrupts the stringent balance between pro- and anti-inflammatory cytokines, increasing neuroinflammation, which contributes to neurodegenerative diseases. The aging brain is particularly vulnerable to infections due to a weakened and compromised immune response and impaired integrity of the...
Maternal malnutrition induces inflammatory pathways and oxidative stress in the dorsolateral prostate of male offspring rats
Maternal conditions during pregnancy can influence the long-term health of offspring. In particular, maternal malnutrition (MM), such as protein restriction, affects the development of several organs, including the male reproductive system. This study examined how a low-protein maternal diet impacts the structure and function of the dorsolateral prostate (DLP) in aging male rats. Male offspring were divided into two groups: A control group (CTR), whose mothers received a normal protein diet...
Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics
Sepsis is a life-threatening multiple organ dysfunction resulting from a dysregulated host response to infection, and patients with sepsis always exhibit a state of immune disorder characterized by both overwhelming inflammation and immunosuppression. The aging of immune system, namely "immunosenescence", has been reported to be correlated with high morbidity and mortality in elderly patients with sepsis. Initially, immunosenescence was considered as a range of age-related alterations in the...
Cross-sectional associations of epigenetic clocks with intrinsic capacity and functional ability in older adults with frailty and cognitive impairment: the COGFRAIL study
Functional ability and intrinsic capacity (IC) have been proposed as determinants of healthy aging, but the extent to which these indicators are affected by biological aging remains unknown. We explored the association of biological age acceleration (BAA) with functional ability and IC in older adults with physical and cognitive impairments. This cross-sectional study used data from 163 individuals (84.0 ± 5.2 years [range 72-99], 61.8% women) of the COGFRAIL cohort. Functional ability on basic...
Uracil-induced replication stress drives mutations, genome instability, anti-cancer treatment efficacy, and resistance
Uracil incorporation into DNA, as a result of nucleotide pool imbalances or cytosine deamination (e.g., through APOBEC3A/3B), can result in replication stress and is the most common source of mutations in cancer and aging. Despite the critical role of uracil in genome instability, cancer development, and cancer therapy, only now is there emerging data on its impact on fundamental processes such as DNA replication and genome stability. Removal of uracil from DNA by base excision repair (BER) can...
Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients
Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double-blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre-surgery through hospital discharge. Primary...
Changes in Home Care Clients' Sensory Impairment Status and Its Association With Functioning Over 18 Months: A Longitudinal Register-Based Study
We investigated the changes in home care clients' vision and hearing over 18 months and examined the role of sensory impairments in maintaining their functioning. We used data from the Finnish Resident Assessment Instrument (RAI) database (n = 7013). Sensory impairment status was categorized by type (single or dual) and severity (mild or moderate/severe). The association between sensory impairment and functioning over 18 months was examined using binary logistic regression analysis with...
Nuclear Import Defects Drive Cell Cycle Dysregulation in Neurodegeneration
Neurodegenerative diseases (NDDs) and other age-related disorders have been classically defined by a set of key pathological hallmarks. Two of these hallmarks, cell cycle dysregulation (CCD) and nucleocytoplasmic transport (NCT) defects, have long been debated as being either causal or consequential in the pathology of accelerated aging. Specifically, aberrant cell cycle activation in post-mitotic neurons has been shown to trigger neuronal cell death pathways and cellular senescence....
Effect of the 2018 Japan floods and COVID-19 pandemic on cognitive decline among atomic bomb survivors in Hiroshima, Japan: a retrospective cohort study
CONCLUSIONS: ABSs had a reduced risk of cognitive decline during the pandemic compared with that of the other groups.
The association between the number of teeth and frailty among older adults: a systematic review and meta-analysis
CONCLUSIONS: There is a significant association between tooth count and frailty, particularly in those with 20 or fewer teeth. Policymakers should prioritize oral health within aging populations by promoting early preventive care and education to mitigate frailty risk. Robust, large-scale studies are needed to guide evidence-based interventions and public health policy.
Longitudinal effects of diet quality on healthy aging - Focus on cardiometabolic health: findings from the Canadian longitudinal study on aging (CLSA)
BACKGROUND: Hypertension, a major concern for older adults, contributes to morbidity and mortality by increasing the risk of cardiovascular disease, stroke, kidney dysfunction, and cognitive decline. A healthy diet plays a vital role in limiting chronic disease progression in aging populations.
Causal relationship between molecular markers of biological aging and orthopedic diseases: A two-sample bidirectional Mendelian randomization study
CONCLUSIONS: This study suggests a potential causal associations between molecular markers of biological aging and orthopedic diseases, suggesting avenues for future research into the underlying mechanisms.
Immersive Virtual Reality for Older Adults: Challenges and Solutions in Basic Research and Clinical Applications
Immersive virtual reality (IVR) offers significant potential for aging research, providing a controlled yet ecologically valid platform for studying cognitive, emotional, and motor processes, as well as supporting interventions and diagnostic assessments in older adults. However, its usability can be hindered by age-related sensory, motor, and cognitive changes, which may contribute to anxiety, disorientation, and reduced task engagement. In this narrative review, we examine the challenges older...
The genetic risk factors, molecular pathways, microRNAs, and the gut microbiome in Alzheimer's disease
Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. It is a multifaceted condition resulting from interplay of genetic mutations (e.g., APP, PSEN1, PSEN2) that account for less than 5% of cases, several genetic risk variants such as APOE4, TREM2, CD33, CLU, SORL1, and CR1 contribute to disease susceptibility and epigenetic factors, which may mediate the influence of environmental and lifestyle factors over time. Other critical contributors such as aging, protein misfolding...
Aging and Longevity: Latest results from PubMed
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