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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...

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...

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.

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...

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....

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...

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...

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...

Osteoarthritis (OA) is the most common age-induced degenerative joint disease associated with synovial inflammation, subchondral bone remodeling, and cartilage degradation. One of the significant emerging causes of OA progression is senescent cell accumulation within the joint compartment during lifespan. Currently, there are no therapeutic approaches nor stratification tools that rely on the senescence burden in OA. In this study, we identified the b-series ganglioside 3 (GD3) as new senescent...

Frailty is a major health concern associated with aging and has been linked to gut microbiome composition, especially in elderly individuals needing care. People with HIV (PWH) present high risk of early-onset frailty. This study examines the relationship between frailty and the gut microbiome, with an emphasis on sex-based differences in PWH. Data were drawn from 268 participants in the New Orleans Alcohol Use in HIV (NOAH) Study, including 16S microbiome sequencing from stool samples, cytokine...

Biological aging clocks across organ systems and tissues have advanced understanding of human aging and disease. In this study, we expand this framework to develop seven magnetic resonance imaging-based multi-organ biological age gaps (MRIBAGs), including the brain, heart, liver, adipose tissue, spleen, kidney and pancreas. Using data from 313,645 individuals curated by the MULTI Consortium, we link the seven MRIBAGs to 2,923 plasma proteins, 327 metabolites and 6,477,810 common genetic...

Parkinson's disease (PD) has been associated with alterations in neuronal activity in the basal ganglia-thalamocortical (BGTC) network. Previous studies have suggested that cortical disinhibition is a feature of PD, but there has been little direct evidence of the changes in cortical neuronal spiking activity to support this hypothesis. To test the hypothesis that activity in the motor cortex is enhanced in PD, we investigated the effects of parkinsonism on movement-related neuronal activity in...

Parkinson's disease (PD) is a most common neurodegenerative disorder caused by genetic, epigenetic, and environmental factors. DNA methylation, regulated by DNA methyltransferases (DNMTs) is the key epigenetic modification playing an important role in gene expression regulation. Oligomeric alpha-synuclein - a major neurotoxic agent in PD - could sequester DNMT1 from the cell nucleus to the cytoplasm leading to global DNA hypomethylation. Here we evaluated DNMT1 expression (mRNA, protein),...

Parkinson's disease (PD) is being increasingly recognized for its complex clinical symptoms, including cognitive impairment, which are linked to dynamic changes in brain network configuration and genetic susceptibility. However, the time-varying patterns of network reconfiguration in patients with PD and their relationship with gene expression profiles and cognitive function remain unclear. To address this gap, we analyzed modular variability (MV) in time-varying brain networks-comparing group...

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...

No abstract

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...

Deep brain stimulation (DBS) effectively treats drug-resistant neurological and psychiatric disorders, yet its mechanisms remain unclear. Here we show that high-frequency DBS of the subthalamic nucleus (STN), a common target for Parkinson's disease (PD), activates afferent axons while inhibiting STN neurons. These contrasting presynaptic and postsynaptic effects arise from a decrease in local neurotransmitter release with a larger decrease in glutamate than GABA, shifting the...

Biological aging clocks across organ systems and tissues have advanced understanding of human aging and disease. In this study, we expand this framework to develop seven magnetic resonance imaging-based multi-organ biological age gaps (MRIBAGs), including the brain, heart, liver, adipose tissue, spleen, kidney and pancreas. Using data from 313,645 individuals curated by the MULTI Consortium, we link the seven MRIBAGs to 2,923 plasma proteins, 327 metabolites and 6,477,810 common genetic...

No abstract