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Extensive studies indicate that mitochondria dysfunction is pivotal for Alzheimer's disease (AD) pathogenesis; while cumulative evidence suggests that increased mitochondrial stress response (MSR) may mitigate neurodegeneration in AD, explorations to develop a MSR-targeted therapeutic strategy against AD are scarce. We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which NAD^(+)-boosting agent nicotinamide mononucleotide (NMN)...

One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models accurately mimicking the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside neurons that synthesize catecholamines. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkinson's, Alzheimer's and apparently healthy aging individuals. However, this brain pigment is not taken into consideration in current animal...

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Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority of patients experience long-term disease control. Using a large, clinically annotated cohort of patients with metastatic hormone receptor-positive (HR+) breast cancer, we identify TP53 loss (27.6%) and MDM2 amplification (6.4%) to be associated with lack of long-term disease control. Human breast cancer models reveal that p53 loss does not alter CDK4/6 activity or G1 blockade but instead...

One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models accurately mimicking the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside neurons that synthesize catecholamines. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkinson's, Alzheimer's and apparently healthy aging individuals. However, this brain pigment is not taken into consideration in current animal...

Elaborating and understanding disparities in the burden of cardiovascular disease attributable to high fasting plasma glucose is important to improve diabetes prevention and promote cardiovascular health. In this study, we pool data on 791,373 people aged 25 years and older from three population-based surveys, and estimate the burden of cardiovascular disease attributable to high fasting plasma glucose between 2010 and 2018 in China by age, sex, region and socio-demographic index. In 2018, an...

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CONCLUSION: The simultaneous examination of a broad range of potential predictors revealed that longevity can be achieved under very different conditions and is achieved by heterogeneous groups of people.

BACKGROUND: The worldwide number of adults aged 60 years and older is expected to double from 1 billion in 2019 to 2.1 billion by 2050. As the population lives longer, the rising incidence of chronic diseases, cognitive disorders, and behavioral health issues threaten older adults' health span. Exercising, getting sufficient sleep, and staying mentally and socially active can improve quality of life, increase independence, and potentially lower the risk for Alzheimer's disease or other...

The intricate spatial configurations of brain networks offer essential insights into understanding the specific patterns of brain abnormalities and the underlying biological mechanisms associated with Alzheimer's disease (AD), normal aging, and other neurodegenerative disorders. This study investigated alterations in the topographical structure of the brain related to aging and neurodegenerative diseases by analyzing brain gradients derived from structural MRI data across multiple cohorts (n =...

Usage of the phrase "biological age" has picked up considerably since the advent of aging clocks and it has become commonplace to describe an aging clock's output as biological age. In contrast to this labeling, biological age is also often depicted as a more abstract concept that helps explain how individuals are aging internally, externally, and functionally. Given that the bulk of molecular aging is tissue-specific and aging itself is a remarkably complex, multifarious process, it is...

Ischemic stroke and cerebral amyloid angiopathy (CAA) pose significant challenges in an aging population, particularly in post-stroke recovery. Using the 5xFAD mouse model, we explore the relationship between CAA, ischemic stroke, and tissue recovery. We hypothesize that amyloid-beta accumulation worsens stroke outcomes by inducing blood-brain barrier (BBB) dysfunction, leading to impaired neurogenesis. Our findings show that CAA exacerbates stroke outcomes, with mice exhibiting constricted BBB...

The intricate spatial configurations of brain networks offer essential insights into understanding the specific patterns of brain abnormalities and the underlying biological mechanisms associated with Alzheimer's disease (AD), normal aging, and other neurodegenerative disorders. This study investigated alterations in the topographical structure of the brain related to aging and neurodegenerative diseases by analyzing brain gradients derived from structural MRI data across multiple cohorts (n =...

Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system, and elucidating its pathogenesis remains challenging. In this study, we used the inverse-variance weighted (IVW) model as the major analysis method to perform hypothesis-free Mendelian randomization (MR) analysis on the data from MRC IEU OpenGWAS (18,097 exposure traits and 16 AD outcome traits), and conducted sensitivity analysis with six models, to assess the robustness of the IVW results, to identify...

CONCLUSION: Stroke accelerates the brain aging process, even in patients with relatively small-volume infarcts. This phenomenon is particularly accentuated in elderly patients, and both stroke severity and poststroke functional outcomes are closely associated with accelerated brain aging. Further studies are needed to explore the mechanisms underlying the accelerated brain aging observed in stroke patients, with a particular focus on the structural alterations and plasticity of the brain...

A member of the Nobel Committee for Chemistry shares her perspective on how she and others are trying to expand the nomination pool for the famed awards