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Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies due to their self-renewal and differentiation capabilities. Pathological microenvironments expose MSCs to senescence-inducing factors such as reactive oxygen species (ROS), resulting in MSC functional decline and loss of stemness. Oxidative stress leads to mitochondrial dysfunction, a hallmark of senescence, and is prevalent in aging tissues characterized by elevated ROS levels. We hypothesized that overexpression...

Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses. We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages...

Synaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's disease (PD), occurring before widespread protein aggregation, neuronal loss, and cognitive decline. While the field has focused on the aggregation of Tau and α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even before their aggregation. Therefore, understanding the mechanisms by which Tau and α-Syn affect presynaptic terminals...

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Alzheimer's disease (AD) is the most common form of dementia. Mutations in genes and precursors of β amyloid (Aβ) are found in the familial form of the disease. This led to the evaluation of seven monoclonal antibodies against Aβ in subjects with AD, two of which were approved for use by the FDA. They caused only a small improvement in cognitive function, probably because they were given to those with much more prevalent sporadic forms of dementia. They also have potentially serious adverse...

Little evidence exists regarding the associations between clinical parameter-based biological aging and the incidence and outcome of chronic kidney disease (CKD). Thus, we aimed to assess the associations between biological aging, genetic risk, and the risk of CKD, as well as investigate the impact of accelerated biological aging on life expectancy. 281,363 participants free of kidney diseases from the UK Biobank were included in this prospective study. Biological age was measured from clinical...

Michael Kratsios and Lynne Parker would reprise their roles in first Trump administration and work with AI czar

The ability to prioritize among input features according to relevance enables adaptive behaviors across the human lifespan. However, relevance often remains ambiguous, and such uncertainty increases demands for dynamic control. While both cognitive stability and flexibility decline during healthy ageing, it is unknown whether aging alters how uncertainty impacts perception and decision-making, and if so, via which neural mechanisms. Here, we assess uncertainty adjustment across the adult...

CONCLUSION: The social engagement of the older adults in urban China reflects and is influenced by the wider socio-economic transformation of the country in the recent decades. Financial security afforded by the pension system has lessened the older adults' need to engage in income-generating activities. Combined with an increase in leisure time, this represents a luxury previously unavailable to earlier generations. However, institutional ageism and low digital literacy are important...

CONCLUSION: Self-care and sleep quality are associated with overall happiness. Policymakers and planners should prioritize happiness enhancement by addressing its relationship with sleep and self-care practices.

Endocytosis, required for the uptake of receptors and their ligands, can also introduce pathological aggregates such as α-synuclein (α-syn) in Parkinson's Disease. We show here the unexpected presence of intrinsically perforated endolysosomes in neurons, suggesting involvement in the genesis of toxic α-syn aggregates induced by internalized preformed fibrils (PFFs). Aggregation of endogenous α-syn in late endosomes and lysosomes of human iPSC-derived neurons (iNs), seeded by internalized α-syn...

Parkinson's disease (PD) is a multifactorial disease caused by irreversible progressive loss of dopaminergic neurons (DANs). Recent studies have reported the successful conversion of astrocytes into DANs by repressing polypyrimidine tract binding protein 1 (PTBP1), which led to the rescue of motor symptoms in a chemically-induced mouse model of PD. However, follow-up studies have questioned the validity of this astrocyte-to-DAN conversion model. Here, we devised an adenine base editing strategy...

CONCLUSION: The downregulation of many genes is a major contributor to brain aging and neurodegeneration. High levels of physical activity have been shown to effectively reactivate these genes, making it a promising strategy to slow brain aging.

Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. Protein homeostasis (proteostasis) depends on a core network of factors directly influencing protein production, folding, trafficking, and degradation. Cellular proteostasis also depends on the overall composition of the proteome and numerous environmental variables. Modulating this cellular proteostasis state can influence the stability of multiple endogenous proteins, yet the factors...

The aim of the present study is to investigate differences in brain networks modulation during the pre- and post-sleep onset period, both within and between two groups of young and older individuals. Thirty-six healthy elderly and 40 young subjects participated. EEG signals were recorded during pre- and post-sleep onset periods and functional connectivity analysis, specifically focusing on the small world (SW) index, applied to EEG data (i.e., frequency bands) was examined. Significant...