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The sensory motor cortex (SMC) plays a crucial role in motor function and is implicated in the pathophysiology of idiopathic Parkinson's disease (iPD). Asymmetric motor symptomatology in iPD suggests lateralized neurochemical alterations that may underlie disease progression and severity. Single-voxel in vivo proton magnetic resonance spectroscopy using PRESS (20 × 20 × 20 mm³) and MEGA-PRESS (30 × 30 × 30 mm3) sequences were performed on bilateral SMC in 25 iPD patients and 23 healthy controls...

Biological phenotypes emerge from complex interactions across molecular layers. Yet, data-driven approaches to infer these regulatory networks have primarily focused on single-omic studies, overlooking inter-layer regulatory relationships. To address these limitations, we developed MINIE, a computational method that integrates multi-omic data from bulk metabolomics and single-cell transcriptomics through a Bayesian regression approach that explicitly models the timescale separation between...

Chaperone-mediated autophagy (CMA) declines in ageing and neurodegenerative diseases. Loss of CMA in neurons leads to neurodegeneration and behavioural changes in mice but the role of CMA in neuronal physiology is largely unknown. Here we show that CMA deficiency causes neuronal hyperactivity, increased seizure susceptibility and disrupted calcium homeostasis. Pre-synaptic neurotransmitter release and NMDA receptor-mediated transmission were enhanced in CMA-deficient females, whereas males...

Liquid-liquid phase separation (LLPS) and subsequent liquid-gel/solid transition are considered common aggregation mechanisms of proteins linked to neurodegenerative diseases. α-synuclein (α-syn), the main factor in Parkinson's disease pathology, has been reported to undergo LLPS, thereby accelerating aggregate formation. However, the precise molecular events involved in the early stages of α-syn aggregation remain controversial. In this study, we show that α-syn aggregation is promoted by...

Age and APOE ε4 are major risk factors for Alzheimer's disease (AD), while sex differences exist in disease prevalence and progression. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and AD. To examine proteomic changes due to age, sex and apolipoprotein E (APOE) ε4 along with amyloid status before clinical AD occurs, we profiled 6,175 proteins in the CSF from 994 cognitively normal individuals aged 43-91 years. We identified and replicated 2,172...

Non-enzymatic reactions in glycolysis produce methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been hypothesized to drive obesity, diabetes, and aging-associated pathologies. A combination of nicotinamide, α-lipoic acid, thiamine, pyridoxamine, and piperine (Gly-Low) lowers the deleterious effects of glycation by reducing MGO and the MGO-derived AGE, MG-H1, in mice. Gly-Low supplementation in the diet reduces food consumption, decreases body weight...

CONCLUSION: Evaluation of a person's IC at baseline explains additional variance compared to traditional frailty measures when predicting the risk of future negative health outcomes such as dementia incidence and mortality.

Chaperone-mediated autophagy (CMA) declines in ageing and neurodegenerative diseases. Loss of CMA in neurons leads to neurodegeneration and behavioural changes in mice but the role of CMA in neuronal physiology is largely unknown. Here we show that CMA deficiency causes neuronal hyperactivity, increased seizure susceptibility and disrupted calcium homeostasis. Pre-synaptic neurotransmitter release and NMDA receptor-mediated transmission were enhanced in CMA-deficient females, whereas males...

Age increases of brain amyloid plaques may be mediated by prior increase of soluble Aβ42. Here, we show that frontal cortex samples from brains of cognitively normal aging humans had progressively increased levels of soluble amyloid peptide Aβ40 throughout the lifespan. Aggregated amyloid fraction was subsequently obtained by formic acid, where Aβ42 showed increases only in humans over 90 years old when compared to those younger than 50. Similarly, aging wild-type mice without amyloid plaques...

Age and APOE ε4 are major risk factors for Alzheimer's disease (AD), while sex differences exist in disease prevalence and progression. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and AD. To examine proteomic changes due to age, sex and apolipoprotein E (APOE) ε4 along with amyloid status before clinical AD occurs, we profiled 6,175 proteins in the CSF from 994 cognitively normal individuals aged 43-91 years. We identified and replicated 2,172...

Tissue-specific endothelial cells (ECs) regulate metabolism, inflammation, coagulation, organ development and regeneration. However, therapeutic application of EC transplantation requires scalable expansion of engraftable ECs that sustain their angiogenic and angiocrine functions. Here we identify a non-canonical aryl hydrocarbon receptor (AHR) pathway switched on by canonical AHR inhibitors that reactivates quiescent EC proliferation. Incubation of tissue-specific human ECs with AHR inhibitors,...

CONCLUSIONS: Our findings underscore the need for cross-national interventions that strengthen social support, increase opportunities for social participation, improve welfare provisions, and foster social integration to mitigate the cognitive health risks posed by social isolation, thereby promoting healthy aging globally.

CONCLUSIONS: This trial showed no significant improvements in cognitive and psychological outcomes after the PICMOA intervention. However, the findings raise important considerations regarding participants' familiarity with digital devices and intervention setting. Further research is needed to accumulate evidence on the duration and intensity of intervention and individual support for improving digital literacy.

Nicotinamide adenine dinucleotide (NAD^(+)) is an essential molecule involved in cellular metabolism, and its decline has been implicated in ageing and age-related disorders. However, evidence for an age-related decline in NAD^(+) levels in humans has been consistently observed only in a limited number of studies. Similarly, although preclinical studies support the idea that supplementation with NAD^(+) precursors is a promising therapeutic strategy to promote healthy ageing, human clinical...

CONCLUSION: Our findings suggest that a higher DDS was associated with a lower risk of disability in ADL among older Chinese adults. Greater efforts to promote a diverse diet should be targeted towards older adult for preventing disability in ADL.

Birch bark tar, used as chewing gum and glue, provides rare window into life 6000 years ago

Scientists reopen the case of “splatatouille”