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Pathologic α-synuclein (α-syn) aggregates from the gastrointestinal (GI) tract may contribute to Parkinson's disease (PD). Xiang et al.¹ report in Neuron that enteric nervous system-specific expression of asparaginyl endopeptidase (AEP)-truncated α-syn and tau spreads to the brain, synergistically causing PD-related neurodegeneration and neurobehavioral deficits.

Alzheimer's disease (AD) is a pervasive neurodegenerative disorder, and new approaches for its prevention and therapy are critically needed. Here, we elucidate a gut-microbiome-brain axis that offers actionable perspectives for achieving this objective. Using the 5xFAD mouse model, we identify increased Clostridium abundance and decreased Bacteroides abundance as key features associated with β-amyloid (Aβ) burden. Treatment with Bacteroides ovatus, or its associated metabolite...

RE-1 silencing transcription factor (REST) is a key repressor of neural genes. REST is upregulated under stress signals, aging and neurodegenerative diseases, but although it is upregulated, its function is lost in Alzheimer's Disease. However, why it becomes inactive remains unclear. Here, we show that the NAD-dependent deacetylase SIRT6 regulates REST expression, location and activity. In the absence of SIRT6, REST is overexpressed but mislocalized, leading to a partial loss of its activity...

Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD) patients show potential as biomarkers for brain degeneration. To investigate AD-specific PLR and its underlying neuromodulatory sources, we combine high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( P c ) and...

Frictional slip between bodies having different elastic or geometrical properties (bimaterial interfaces) creates a unique type of rupture, bimaterial "slip pulses." These slip pulses propagate along the interfaces separating elastically different contacting bodies. They exhibit highly localized slip with accompanying local normal stress reduction. These pulses do not result from properties of "friction laws" but, instead, are formed via the elastic mismatch of the contacting bodies. Here, we...

Epigenetic age quantifies biological age using DNA methylation information and is a potential pathway by which physical activity benefits general health. We aimed to assess the cross-sectional and longitudinal associations between physical activity and epigenetic age in middle-aged and older Australians. Blood DNA methylation data for 6208 participants (40% female) in the Melbourne Collaborative Cohort Study (MCCS) were available at baseline (1990-1994, mean age, 59 years) and, of those, for...

Aging is often accompanied by changes in brain structure and executive functions, particularly in tasks involving cognitive flexibility, such as task-switching. However, substantial individual differences in the degree of cognitive impairment indicate that some individuals can cope with brain changes more effectively than others, suggesting higher cognitive reserve (CR). This study identified a neural basis for CR by examining the longitudinal relationship between task-related brain activation,...

The cellular proteome determines the functional state of cells and is often skewed to direct pathological conditions. Autophagy shapes cellular proteomes primarily through lysosomal degradation of either damaged or unnecessary proteins. Here, we show that autophagy directs the senescence-specific translatome to fuel inflammation by coupling selective protein degradation with alternative splicing. RNA splicing is significantly altered during senescence, some of which surprisingly depend on...

Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. This study aims to investigate the potential role and mechanisms of BRD7 in ALS. We analyzed RNA levels using qRT-PCR, protein levels through immunofluorescence and western blot, and apoptosis via TUNEL staining. Cell transfection was conducted...

RE-1 silencing transcription factor (REST) is a key repressor of neural genes. REST is upregulated under stress signals, aging and neurodegenerative diseases, but although it is upregulated, its function is lost in Alzheimer's Disease. However, why it becomes inactive remains unclear. Here, we show that the NAD-dependent deacetylase SIRT6 regulates REST expression, location and activity. In the absence of SIRT6, REST is overexpressed but mislocalized, leading to a partial loss of its activity...

It has been established that N-acetyltransferase (murine NAT1 (mNAT1) and human NAT2 (hNAT2)) mediates insulin sensitivity in type 2 diabetes. Here we show that mNAT1 deficiency leads to a decrease in cellular spermidine-a natural polyamine exhibiting health-protective and anti-ageing effects-but understanding of its mechanism is limited. We identify that mNAT1 and hNAT2 modulate a type of post-translational modification involving acetylated spermidine, which we name acetylhypusination, on...

CONCLUSION: This study suggested that, approximately one-quarter of older persons suffered from CI in Gansu, China. Low SES was substantially associated with risk of CI. Although interventions to modify traditional risk factors may decrease the risk of CI, disparities by SES may remain without addressing SES itself.

CONCLUSIONS: Reducing physical frailty in older adults, reducing their sense of loneliness, and enhancing their family health is essential, as it can increase their levels of confidence with regard to ageing at home.

CONCLUSION: Biological phenotypes might be used to identify different clinical and functional phenotypes in individuals affected by COVID-19.

CONCLUSION: The two most vulnerable aspects of OHL in medical institutions regarding the needs of older patients are health information and communication. The factors influencing the construction of OHL in medical institutions are multifaceted, encompassing micro, meso, and macro levels. At the macro level, it is essential for medical institutions to enhance leadership awareness of OHL and to incorporate its development into institutional strategic plans. At the meso-level, medical institutions...

Ancient DNA reveals victims may not have spent their last moments with close family, as long suspected

No abstract

CONCLUSIONS: This study identified several associated factors with the OB of CGs of persons with dementia. Specifically, we remarked that the CGs' education, employment status, household chores assistance, overload presence, psychological distress symptoms and the functional level of the person with dementia who cared for were important variables that should be considered when evaluating OB or creating OB-related interventions in CGs.