Aging & Longevity

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...

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...

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...

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...

Brain aging represents a critical risk factor for neurodegenerative diseases and cognitive decline, yet the measurement of biological brain age remains challenging. Brain aging clocks, which quantify the discrepancy between predicted brain age and chronological age, have emerged as powerful tools for assessing brain health and predicting disease outcomes. Recent advances have transformed these clocks from simple global metrics to sophisticated, multi-modal approaches that capture regional...

Global population aging challenges acute, disease-centric healthcare models and highlights the need for functional markers of aging. The World Health Organization's intrinsic capacity (IC) framework, encompassing cognition, vitality, locomotion, psychological well-being, and sensory function, provides a multidimensional measure of functional reserve. However, most longitudinal studies have collapsed IC into a single score, limiting insight into domain-specific trajectories and...

Skeletal muscle aging is associated with increased lipid accumulation, or myosteatosis, leading to lipotoxicity and loss of muscle function. Here, we report that loss of the lactate receptor GPR81 in cellular and progeroid models of muscle aging is associated with impaired lipid oxidation and enhanced lipid accumulation. Knockdown of GPR81 in young healthy myoblasts led to an increase in senescence hallmarks such as DNA damage, accumulation of reactive oxygen species (ROS), impaired...

INTRODUCTION: Atrial fibrillation (AF) is associated with cognitive decline and dementia even in the absence of clinical stroke, potentially through mechanisms such as silent infarction, small-vessel disease, hypoperfusion, and systemic inflammation. However, most previous studies have focused on global brain measures, and little is known about region-specific structural alterations, particularly within deep gray-matter structures and hippocampal subfields. Evidence regarding atrial flutter...

INTRODUCTION: Mild cognitive impairment (MCI) is frequently accompanied by impairments in postural control and trunk muscle function. Although gamma-theta rhythmic stimulation has been reported to modulate neural oscillatory activity, its influence on brain-muscle interactions in individuals with MCI remains poorly understood. This exploratory pilot study investigated whether changes in EEG connectivity following gamma-theta stimulation were associated with alterations in trunk muscle...

INTRODUCTION: Age-related motor decline is particularly evident during complex movements that require sequencing and bimanual coordination. The one-target advantage (OTA), in which single-target movements are typically initiated faster than the first segment of a two-target sequence, provides a useful framework for assessing planning demands in older adults.

Aging-related neurological disorders, including stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and various neuroinflammatory conditions, affect over three billion individuals worldwide and constitute leading causes of morbidity, disability, and socioeconomic burdens. Aging contributes not only to the increased incidence of these disorders but also to their progression through interconnected mechanisms, including endothelial dysfunction, oxidative stress, chronic...

Local brain age (LBA) is a spatially resolved biomarker of brain aging that captures regional deviations from chronological age, yet its genetic architecture in the subcortex remains unexplored. Here, we present the first genome-wide association study (GWAS) of subcortical LBA, estimated using a deep neural network applied to T1-weighted MRI scans from 41,957 cognitively normal participants in the UK Biobank. We computed LBA across 14 subcortical structures and identified 14 significant...

Amyloid-β (Aβ) accumulation begins many years before the onset of clinical symptoms in Alzheimer's disease (AD). Studies in humans suggest that unimpaired individuals with elevated Aβ exhibit subtle changes in cognitive trajectories over time, particularly in memory. Identifying animal models that recapitulate these early changes is critical for translational research on preclinical AD. Here, we hypothesized that aging dogs, which naturally accumulate Aβ, show similar patterns to those observed...

As a major contributor to cardiac diseases, thrombosis, a pathological process in which the formation of a blood clot restricts blood flow, is a leading cause of mortality worldwide. A central event in thrombosis involves thrombin-mediated cleavage of soluble fibrinogen into fibrin monomers, which polymerize into an insoluble fibrin mesh that forms the thrombus. While the risk of thrombosis increases markedly with age, the underlying cellular mechanisms linking aging and thrombus formation...

Social engagement is thought to support reserve and resilience in aging, yet prior findings suggest it may relate differently, potentially even in opposite directions, in males and females. To further understand these differences, we investigated psychological and biological correlates of social network within each sex, and tested whether its association with cognition differs by sex. Social network was assessed in 104 older adults (age 73.77 ± 3.58, 60 females) using the Social Network Index...