Aggregator

Neuroinflammation is a pathological feature of neurodegenerative diseases like Alzheimer's disease and ALS. Cytoplasmic dsRNA (cdsRNA) triggers a type-I interferon response in human neural cells, leading to their death, and is found in neurons of C9ORF72-ALS patients. Here, we report the spatial coincidence of cdsRNA and pTDP-43 inclusions in human postmortem tissue with Alzheimer's disease pathology, and upregulated interferon response genes in affected regions. CdsRNA also accumulates in a...

Multiple drivers of global change are causing rapid biodiversity loss worldwide. However, predicting species' trajectories remains challenging due to the dynamic and state-dependent nature of ecological responses in real-world ecosystems. Here, we leverage nonlinear time series analysis of a multi-decadal, high-resolution dataset encompassing climate, freshwater, and sediment variables, alongside estuarine macroinvertebrate abundance. Our analysis shows that key biological traits, including body...

The RNA-binding protein FUS is commonly mutated in familial cases of amyotrophic lateral sclerosis (ALS-FUS), where it forms cytoplasmic inclusions. In addition, non-mutated FUS is a constituent component of protein inclusions in approximately 5-10% of cases of frontotemporal lobar degeneration (FTLD). Overexpression of wild-type human FUS is toxic to Drosophila neurons, preventing normal development and shortening lifespan in adults. In this study, we demonstrated that removal of the nuclear...

Mitochondria provide energy and maintain homeostasis, and their dysfunction relates to aging. Disrupted structure and function of mitochondria are linked to age-related diseases, but the roles of many mitochondrial proteins in mitochondrial dynamics and aging remain unclear. We studied the role of the mitochondrial fission protein MTP-18 in mitochondrial dynamics and aging in C. elegans. Our data show that loss of mtp-18 increases longevity and stress resistance, alongside changes in key...

Chronic d-galactose (d-gal) injection is an experimental model of accelerated aging in rodents. However, the cardiovascular phenotypes of this model have been poorly characterized, especially as they relate to sex differences. The goal of this study was to investigate the cardiovascular effects of chronic d-gal injection in male and female C57BL/6 mice and the impact of HO-1 induction or inhibition in this model. Forty-eight 8-week-old male and female C57BL/6 mice were divided randomly into four...

Epidemiological studies consistently link higher fish intake with slower rates of cognitive decline and lower dementia incidence. The aim of the present study was to systematically review existing observational studies investigating the association between fish consumption and cognitive function in older adults. A total of 25 studies (8 cross-sectional and 17 prospective including mainly healthy older adults, age range of participants ranging from 18 to 30 years at baseline in prospective...

No abstract

Flower aging, or senescence, is generally accompanied by petal dehydration/wilting. The cuticle functions as a barrier to withhold water for plant organs. However, little is known about how the cuticle modifies the process of petal development. Here, we report that cuticular wax is dynamically changed during petal senescence and wax coverage on petals is coordinated with the expression of TgWIN1. Functional identification indicates that TgWIN1 positively regulates wax accumulation and delays...

The protein-level functionalities of the human gut microbiota in large populations, and their associations with host factors, remain unexplored. This study reports a metaproteomic study of 1,967 fecal samples from 1,399 middle-aged and elderly Chinese individuals, identifying microbial functions linked to 44 phenotypes. We uncover aging-associated functional shifts in carbon metabolism and energy production driven by species within the Bacillota, Bacteroidota, Actinomycetota, and Pseudomonadota....

Lactate, once viewed merely as a glycolytic byproduct, is now recognized as a key signaling molecule and epigenetic regulator through the recently identified post-translational modification known as lactylation. In diabetic microvascular complications, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic peripheral neuropathy (DPN), persistent hyperglycemia promotes metabolic reprogramming toward glycolysis and leads to excessive lactate production. This sustained...

Type 1 diabetes, particularly with childhood onset, is associated with altered neurocognitive traits, yet the underlying biological mechanisms are unclear. Here, we integrate genome-wide association results with single-cell epigenomic profiles and show that type 1 diabetes heritability is enriched in accessible chromatin of human brain-resident cells, most notably microglia, across neurodevelopment into adulthood. Bonferroni-corrected cross-trait genetic correlation analyses reveal negative...

Aging is the strongest risk factor for chronic diseases such as cardiovascular disease, Alzheimer's, and cancer. DNA methylation (DNAm) clocks offer a promising measure of biological age, but most rely on linear models that miss non-linear dynamics and CpG interactions. To address this, we developed a deep neural network (DNN)-based DNAm clock trained on 29,167 samples profiled on Illumina EPIC v1.0 and v2.0 arrays. Using 12,234 CpGs selected through sex- and age-stratified correlations, our...

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) but its neural mechanisms remain poorly understood. A mechanistic understanding requires precise characterization of functional responses to various stimulation conditions within the same individual. Here we use 3-T magnetic resonance imaging (MRI)-compatible DBS and precision imaging to collect extensive data from 14 patients with PD who received DBS. Across five timepoints spanning 1 year, each patient...

The connection between aging and immune dysfunction is uncovering how immunoaging processes contribute to disease. Recent data from Alzheimer’s disease, Parkinson’s disease, and adult and pediatric glioblastomas reveal a novel role for TIM3 in brain immune alteration. These findings highlight the role of TIM3 in promoting myeloid cell dysfunction toward an immunosuppressive profile. TIM3-blocking antibody treatments for central nervous system pathologies could be a new therapeutic window for...

Mitochondrial diseases progressively lead to multisystemic failure with treatment options remaining extremely limited. Here, to investigate strategies that alleviate mitochondrial dysfunction, we first generate a ubiquitous and tamoxifen-inducible knockout mouse model of mitochondrial transcription factor A (TFAM), a nuclear-encoded protein involved in mitochondrial DNA (mtDNA) maintenance - Tfam^(fl/fl)Ubc^(Cre-ERT2) (iTfamKO) mice. Systemic TFAM deficiency triggers mitochondrial decline in a...

Aging is the strongest risk factor for chronic diseases such as cardiovascular disease, Alzheimer's, and cancer. DNA methylation (DNAm) clocks offer a promising measure of biological age, but most rely on linear models that miss non-linear dynamics and CpG interactions. To address this, we developed a deep neural network (DNN)-based DNAm clock trained on 29,167 samples profiled on Illumina EPIC v1.0 and v2.0 arrays. Using 12,234 CpGs selected through sex- and age-stratified correlations, our...

Emerging evidence shows that inflammaging varies across populations, challenging universal immune-aging models. Urbanization in sub-Saharan Africa-characterized by reduced exposure to infectious diseases and rising rates of noncommunicable diseases-offers a natural experiment for assessing environmental effects on inflammaging. Lower inflammaging in indigenous groups may reflect adaptation to chronic infection, whereas heightened inflammation in industrialized populations suggests ecological...

Epigenetic clocks derived from DNA methylation patterns are among the most promising biomarkers of biological aging^(1-7), as they capture molecular signatures that predict morbidity and mortality beyond chronological age. Although cross-sectional assessments of epigenetic age have been linked consistently to health outcomes and lifespan, it remains unclear whether the rate of change in these clocks over time provides additional insight into aging trajectories. In this longitudinal study of 699...

CONCLUSIONS: The study highlighted the beneficial role of DASH diet adherence and sustainable nutritional practices in mitigating depressive symptoms and supporting cognitive function in older adults. These dietary patterns could represent crucial components of preventive strategies for healthy aging. Further longitudinal research using objective dietary assessments is needed to clarify causal relationships.

No abstract