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Predicting and preventing Alzheimer's disease

2 months 1 week ago
With all the advances in both the science of aging and artificial intelligence (AI), we are in a propitious position to accurately and precisely determine who is at high risk of developing Alzheimer's disease years before signs of even mild cognitive deficit. It takes at least 20 years for aggregates of misfolded β-amyloid and tau proteins to accumulate in the brain along with neuroinflammation that they incite. This provides a long window of opportunity to get ahead of the pathobiological...
Eric Topol

Modifiable risk factor profiles moderate the effect of beta-amyloid pathology on cognition in aging

2 months 1 week ago
Although modifiable risk factors may account for around 40 % of population variability in dementia risk, the effect of risk factor interrelationships on pathology-cognition relationships is poorly understood. Using risk factor data from a cohort of 203 cognitively normal older adults (73 ± 6.4 years, 56 % female), we used k-means clustering to assign participants to one of three risk-related profiles; namely, positive-active (physical/cognitive activity, education), positive-affective (sleep,...
Mohini Bhade

On the patterns of genetic intra-tumour heterogeneity before and after treatment

2 months 1 week ago
Genetic intra-tumour heterogeneity (gITH) is a universal property of all cancers. It emerges from the interplay of cell division, mutation accumulation and selection with important implications for the evolution of treatment resistance. Theoretical and data-driven approaches extensively studied gITH in ageing somatic tissues or cancers at detection. Yet, the expected patterns of gITH during and after treatment are less well understood. Here, we use stochastic birth-death processes to investigate...
Alexander Stein

Intermittent Supplementation With Fisetin Improves Physical Function and Decreases Cellular Senescence in Skeletal Muscle With Aging: A Comparison to Genetic Clearance of Senescent Cells and Synthetic Senolytic Approaches

2 months 1 week ago
Excess cellular senescence contributes to age-related increases in frailty and reductions in skeletal muscle strength. In the present study, we determined the efficacy of oral intermittent treatment (1 week on-2 weeks off-1 week on) with the natural flavonoid senolytic fisetin to improve frailty and grip strength in old mice. Further, the effects of fisetin on physical function were evaluated in young mice. We performed bulk RNA sequencing of quadricep skeletal muscle to determine the cell...
Kevin O Murray

Research status of visuospatial dysfunction and spatial navigation

2 months 1 week ago
Visuospatial function is a critical aspect of cognitive abilities, encompassing visual perception, attention, memory, and adaptive responses to spatial changes. This paper reviews studies on human visuospatial function, spatial navigation, and factors contributing to visuospatial impairments. After introducing fundamental concepts of visuospatial function and spatial navigation, classical methods for assessing visuospatial performance are summarized. By examining recent advances in spatial...
Rui Bao

Intervention strategies for Parkinson's disease: the role of exercise and mitochondria

2 months 1 week ago
Parkinson's disease (PD), a progressive neurodegenerative disorder with complex pathogenic mechanisms, exhibiting rising prevalence alongside global population aging. Its pathological hallmarks include substantial loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms (e.g., bradykinesia, rigidity) and non-motor manifestations (e.g., cognitive impairment, sleep disorders). Accumulating evidence underscores mitochondrial dysfunction-encompassing reactive...
Ganggang Xu

Attenuation of virulence in Yersinia pestis across three plague pandemics

2 months 1 week ago
Science, Volume 388, Issue 6750, May 2025.
Ravneet Kaur Sidhu, Guillem Mas Fiol, Pierre Lê-Bury, Christian E. Demeure, Emelyne Bougit, Rémi Beau, Charlotte Balière, Aurelia Kwasiborski, Valérie Caro, Jennifer Klunk, Daniel J. Salkeld, Ann Carmichael, Nükhet Varlık, Debi Poinar, David J. D. Earn,…

BRAF oncogenic mutants evade autoinhibition through a common mechanism

2 months 1 week ago
Science, Volume 388, Issue 6750, May 2025.
Hugo Lavoie, Ting Jin, Driss Lajoie, Marion Decossas, Patrick Gendron, Bing Wang, Frantisek Filandr, Malha Sahmi, Chang Hwa Jo, Sandra Weber, Geneviève Arseneault, Sasmita Tripathy, Pierre Beaulieu, Doris A. Schuetz, David C. Schriemer, Anne Marinier,…