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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 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...

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...

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...

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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 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...

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.

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...