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Targeting the NO-cGMP axis in age-related vascular dysfunction: a systematic review and meta-analysis of preclinical animal studies
Vascular dysfunction in aging is driven by multiple interconnected hallmarks of aging, including DNA damage, oxidative stress, chronic inflammation, mitochondrial dysfunction, and cellular senescence and features by endothelial impairment, inflammation, and reduced nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling. Targeting this pathway may offer therapeutic benefit beyond traditional atherosclerosis-focused treatments. A systematic review and meta-analysis were conducted...
A simple supplement could help the immune system fight cancer and viruses
Low arginine levels may allow cancer cells and viruses to slip past the immune system by reducing production of a crucial cellular warning protein. In mice, arginine-rich diets led to fewer colon tumors and milder viral infections, suggesting a simple supplement could have powerful therapeutic potential.
Major highway of the human nervous system gets a complete road map
First comprehensive map of the vagus nerve may point to more precise stimulation therapies
Scientists may have found aging’s hidden trigger for brain disease
Scientists have identified a molecular switch that may help explain why aging makes the brain more vulnerable to diseases such as ALS and Huntington’s. In worms, the protein EPS8 builds up with age and triggers signaling that encourages toxic proteins to clump together, damaging neurons and shortening lifespan. Reducing EPS8 activity prevented these harmful aggregates and preserved nerve function.
Two new compounds could reveal hidden drivers of Alzheimer’s disease
Vanderbilt researchers created the first selective compound designed to inhibit TAOK-1, a poorly understood protein connected to Alzheimer’s disease. They also discovered a second compound that activates the entire TAOK protein family, offering scientists an unexpected new research tool. Together, the compounds could reveal hidden disease mechanisms and point toward new treatment strategies.
Lysosomal dysfunction drives a transcriptional and epigenetic signature found in disease-associated microglia in neurodegenerative diseases
Lysosomal dysfunction is causally linked to neurodegeneration in many lysosomal storage disorders and is associated with various age-related neurodegenerative diseases. Here, we investigated the question of underlying mechanisms using a mouse model of mucopolysaccharidosis type IIIA caused by deficiency of the lysosomal hydrolase SGSH. Systematic imaging and transcriptomic and epigenetic studies revealed microglia to be the most profoundly impacted cell type in brains of Sgsh-deficient mice....
The role of cognitive-motor interaction in landmark reliance and navigational deficits in older adults
Declining spatial navigation abilities are a critical hallmark of aging, where the loss of spatial abilities precedes global cognitive impairment. While navigational decline is traditionally attributed to deficits in higher-order cognitive functions, emerging cognitive-motor frameworks suggest that age-related sensorimotor alterations play a significant, yet previously overlooked, role. Here, we investigate the coupling between locomotor integrity and navigation by combining an immersive...
The BAX/BAK apoptotic checkpoint polices entry to therapy-induced senescence
Cytotoxic chemotherapy is intended to eliminate transformed cells but can also provoke therapy-induced senescence, a persistent and pro-inflammatory cell state that can promote tumor progression. The molecular mechanisms that govern the apoptosis-senescence fate decision remain incompletely understood. Here, we show that the mitochondrial pore-forming proteins BAX and BAK function as a critical checkpoint that restricts entry to therapy-induced senescence. Genetic ablation of BAX and BAK...
Aging at the neurovascular interface: an integrative framework linking cardiovascular and cerebrovascular diseases
Aging is a fundamental driver of cardiovascular and cerebrovascular comorbidities, yet the mechanisms linking aging to concurrent heart and brain diseases remain incompletely understood. The neurovascular interface (NVI) refers to the structural and functional interface through which neural, vascular, and extracellular-matrix signals interact. In the CNS, this concept substantially overlaps with the classical neurovascular unit, whereas in the heart it refers to an emerging heart tissue-specific...
Embracing non-linearity in human ageing
The ageing process is often portrayed as a steady linear decline, as reflected by the methodological frameworks used to study it. Although linear models successfully capture relevant age-related mechanisms, they may fail to identify key transition states occurring during the lifespan. Indeed, ageing entails a series of transitions - from early development, through adolescence, to older age - that are each characterized by distinct biological remodelling events. The study of these underlying...
Deep learning maps local brain aging in relation to cognition across human adulthood
Brain aging, the strongest risk factor for Alzheimer's disease (AD), varies across cortical regions. Global brain age (GBA), an imaging-derived measure of neuroanatomic decline, reduces structural aging to a single summary value. This can potentially obscure regional patterns of cognitive vulnerability preceding AD. This study introduces a deep-learning architecture trained on the [Formula: see text]-weighted MRIs of 14,748 cognitively normal (CN) participants from multiple sites to estimate...
Nuclear garbage disposal: An unexpected role for amyloid precursor protein in Alzheimer's disease
No abstract
Deep learning maps local brain aging in relation to cognition across human adulthood
Brain aging, the strongest risk factor for Alzheimer's disease (AD), varies across cortical regions. Global brain age (GBA), an imaging-derived measure of neuroanatomic decline, reduces structural aging to a single summary value. This can potentially obscure regional patterns of cognitive vulnerability preceding AD. This study introduces a deep-learning architecture trained on the [Formula: see text]-weighted MRIs of 14,748 cognitively normal (CN) participants from multiple sites to estimate...
Endothelial AGGF1 Deficiency Causes Mitochondrial Dysfunction and Contributes to Age-Elevated Blood Pressure
Endothelial cells are critical in the regulation of blood pressure. We previously demonstrated AGGF1 was crucial for maintaining endothelial cell function. This study aims to examine whether AGGF1 regulates blood pressure. Here, we found that AGGF1 expression was inversely correlated with blood pressure with age. In male mice, endothelial-specific loss of function of Aggf1 (Aggf1^(flox/flox)/Tie2-Cre^(+)) significantly increased blood pressure, whereas endothelial-specific human AGGF1...
Relationship Between Hip Fracture and New Onset of Cognitive Impairment Using the National Health and Aging Trends Study
CONCLUSIONS: We were unable to detect a significant association between a hip fracture and new onset of cognitive impairment in older adults. However, conclusions are limited by large confidence intervals. There was a signal toward a positive association, particularly for probable dementia. Future research should be performed in larger sample sizes with rigorous matching to understand risk factors for developing cognitive impairment after hip fracture.
Are exercise benefits in older adults clinically meaningful?: An ancillary and follow-up analysis of a multicenter randomized controlled trial
Physical exercise is beneficial for older adults, but little is known about inter-individual response variability or whether its effects reach clinical significance. We analyzed individual clinically meaningful responses to exercise in older adults. This is an ancillary analysis of a multicenter randomized controlled trial. 188 older patients (> 75 years) with mild cognitive impairment were randomly assigned to a 3-month home-based multicomponent exercise intervention (3-5 days/week based on...