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Translational Remodeling of the Synaptic Proteome During Aging

1 month 2 weeks ago
An important hallmark of aging is the loss of proteostasis, which can lead to the formation of protein aggregates and mitochondrial dysfunction in neurons. Although it is well known that protein synthesis is finely regulated in the brain, especially at synapses, where mRNAs are locally translated in an activity-dependent manner, little is known as to the changes in the synaptic proteome and transcriptome during aging. Therefore, this work aims to elucidate the relationship between the...
Cinzia Caterino

Sulforaphane improves exercise-induced NRF2 signaling in older adults: an in vivo-ex vivo approach

1 month 2 weeks ago
Redox signaling is a key mechanism of exercise-induced adaptation. However, studies have demonstrated impaired responses to acute exercise in older organisms. Adjunctive therapies to augment exercise effects may overcome these deficits. Sulforaphane (SFN), a phytochemical from cruciferous vegetables, stimulates NRF2. This study tested the hypothesis that combining acute exercise (in vivo stimulus) with ex vivo SFN treatment would induce greater NRF2 activation and signaling in older adults...
Dominick J Rodriguez

Estimation of biological age and age-related outcomes with easily accessible parameters in Chinese

1 month 2 weeks ago
Biological aging exhibits significant heterogeneity across individuals, and a precise evaluation at scale is urgently needed. Here, we developed a PCAge, based on common clinical, physiological, and laboratory indices routinely collected in primary healthcare, in the CHARLS. PCAge demonstrated strong correlations with chronological age (r = 0.86-0.88, P < 0.001) and robust performance in the prediction of mortality (C-index = 0.798) over a 10-year follow-up. Biologically older individuals (PCAge...
Yi Li

High-fat diet attenuates vestibular and auditory dysfunction in aged mice via macrophage-mediated anti-inflammatory mechanisms

1 month 2 weeks ago
CONCLUSIONS: HFD mitigates age-related auditory and vestibular impairments by utilizing macrophage-driven anti-inflammatory processes, potentially through polarization towards an M2 phenotype. This research offers fresh perspectives for creating specific treatments, indicating the variable therapeutic possibilities of dietary adjustments in age-related cellular damage. However, the potential metabolic consequences of HFD warrant careful consideration.
Jing Ke

Perineuronal nets in the rodent suprachiasmatic nucleus

1 month 2 weeks ago
The circadian system maintains highly stable rhythms over the lifespan. The precision of the circadian clock emerges from the network organization of the master clock located in the suprachiasmatic nucleus (SCN). Perineuronal nets (PNNs), condensed extracellular matrix structures that are composed of chondroitin sulfate proteoglycans, help maintain synaptic connections in many brain regions after the end of critical developmental periods. We examine here if the SCN of mice, rats and hamsters...
Patricia R Blakely

LCN2 promotes HEI-OC1 cells senescence via activating NF-kappaB signal pathway in presbycusis

1 month 2 weeks ago
Presbycusis, or age-related hearing loss (ARHL), is a prevalent sensory disorder in the elderly, driven by genetic factors, oxidative stress, inflammation responses, and cellular senescence. Despite its significance, the molecular mechanisms underlying ARHL remain poorly defined. In this study, we employed bioinformatic analysis of public gene expression datasets to identify differentially expressed genes in ARHL. Protein-protein interaction network analysis further nominated LCN2 as a hub gene....
Jingjing Wu

A receptor for glycation end products (RAGE) is a key transmitter between garb-aging and inflammaging

1 month 2 weeks ago
A receptor for glycation end products (RAGE) plays a key role in the pathogenesis of many chronic diseases associated with aging. Acting as a multi-ligand sensor, RAGE is able to bind a wide range of stimuli, which fuels inflammation. This makes it a key link between garb-aging and inflammaging. We propose that RAGE functions as the missing molecular link between garb-aging, the progressive buildup of biological waste, and inflammaging, the chronic inflammatory state that drives degenerative...
Zulfiya G Guvatova

Increased nucleotide metabolism alleviates Alzheimer's disease pathology

1 month 2 weeks ago
Genetic information in cells flows from DNA to RNA to proteins, which form molecular machines. During normal ageing, cell intrinsic and environmental factors alter this flow of information by damaging DNA in cells, including postmitotic neurons. Damage to DNA is associated with age-related neurodegenerative diseases such as Alzheimer's disease (AD). We previously reported an increase in DNA repair mechanisms in a fly model of AD. However, the causal mechanisms underlying somatic mutations in AD...
Yizhou Yu

Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel

1 month 2 weeks ago
Sortilin (SORT1) is a lipoprotein receptor that shows genome-wide association with hypercholesterolaemia, explained by its ability to control hepatic output of lipoproteins. Although SORT1 also shows genome-wide association with Alzheimer disease and frontotemporal lobe dementia, the most prevalent forms of age-related dementias, sortilin's contribution to human brain lipid metabolism and health remains unclear. Here we show that sortilin mediates neuronal uptake of polyunsaturated fatty acids...
Anna K Greda