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Introduction Cardiac autonomic dysfunction reduces the cardiac system's ability to respond to stressors and is prevalent in aging and diseases, especially cardiovascular diseases like aortic stenosis (AS). Heart rate variability (HRV) is a common measure for evaluating parasympathetic activity and cardiac autonomic function; similarly, heart rate (HR) changes during exercise are utilized in determining cardiac health. However, directly measuring HR parameters from an electrocardiogram (ECG) is...

The global demographic shift towards an ageing population has rendered cardiovascular ageing and its associated pathologies a growing challenge for health. Emerging evidence highlights the critical role of exercise in mitigating age-associated cardiovascular alterations in structure and function and preventing ageing-associated cardiovascular diseases. However, the precise molecular mechanisms mediating these exercise-induced benefits in promoting healthy cardiovascular ageing remains...

The endocycle is a specialized cell cycle during which cells undergo repeated G/S phases to replicate DNA without division, leading to large polyploid cells. The transition from a mitotic cycle to an endocycle can be triggered by various stresses, which results in unscheduled, or induced endocycling cells (iECs). While iECs can be beneficial for wound healing, they can also be detrimental by impairing tissue growth or promoting cancer. However, the regulation of endocycling and its role in...

Reproductive longevity is essential for female fertility and healthy aging; however, the role of stress response, especially stress granule accumulation, in ovarian aging remains elusive and interventions are lacking. Here, we identified deleterious mutations and decreased expression of NCOA7, a stress-response protein related to granulosa cell senescence in women with physiological and pathological ovarian aging. NCOA7 deletion accelerates oxidative stress-related cellular senescence, ovarian...

This randomized cross-over study examined the acute effects of single-task or dual-task walking physical activity (PA) breaks of prolonged sitting among healthy older adults on cognitive performance and cerebral blood flow velocity (CBFv). Twenty-seven healthy older adults (69.4 ± 5.6 years, 25 female) were randomly assigned to engage in three experimental conditions (i.e., control, single-task, and dual-task walking), each one on a different day. All conditions included 3 h of sitting time,...

CONCLUSIONS: Among older people, all-cause mortality risk significantly increased with the severity of visual and hearing impairments, and the visual and hearing impairments accounted for 10.8% of total deaths. These findings emphasize the importance of vigilant monitoring and management of visual and hearing impairments.

CONCLUSION: Frailty is highly prevalent among older adults in Sari and is associated with a complex interplay of demographic, socioeconomic, and health-related factors. Given the modifiable nature of certain risk factors, targeted interventions focusing on social support, financial stability, and physical activity are essential to mitigate frailty and enhance the quality of life in Iran's aging population.

This study investigates how amyloid pathology influences hippocampal-prefrontal neural dynamics and decision-making in Alzheimer's disease (AD) using 5XFAD mice, a well-established model system characterized by pronounced early amyloid pathology. Utilizing ecologically relevant "approach food-avoid predator" foraging tasks, we show that 5XFAD mice exhibit persistent risk-taking behaviors and reduced adaptability to changing threat conditions, indicative of impaired decision-making....

Imaging genomics offers powerful links between genetics and neuroimaging phenotypes, but conventional methods often lack spatial correspondence. We introduce spatial imaging-transcriptomics, a paradigm that directly integrates magnetic resonance imaging (MRI) and spatially resolved transcriptomics (ST) with matched resolution from the same brain through spatially co-registered maps. We apply this framework to wild-type and Alzheimer's disease (AD) mouse models to uncover the molecular...

Defective mitochondrial quality control in response to loss of mitochondrial membrane polarization is implicated in Parkinson's disease by mutations in PINK1 and PRKN. Parkin-expressing U2 osteosarcoma (U2OS) cells were treated with the depolarizing agents oligomycin and antimycin A (OA) and subjected to cryo-focused ion beam milling and in situ cryo-electron tomography. Mitochondria were fragmented and devoid of matrix calcium phosphate crystals. Phagophores were visualized, with bridge-like...

Aging is a major risk factor for neurodegeneration and is characterized by diverse cellular and molecular hallmarks. To understand the origin of these hallmarks, we studied the effects of aging on the transcriptome, translatome, and proteome in the brain of short-lived killifish. We identified a cascade of events in which aberrant translation pausing led to altered abundance of proteins independently of transcriptional regulation. In particular, aging caused increased ribosome stalling and...

Ribosome stalling drives aging in the killifish brain.

Ubiquitin (Ub), a central regulator of protein turnover, can be phosphorylated by PINK1 (PTEN-induced putative kinase 1) to generate S65-phosphorylated ubiquitin (pUb). Elevated pUb levels have been observed in aged human brains and in Parkinson's disease, but the mechanistic link between pUb elevation and neurodegeneration remains unclear. Here, we demonstrate that pUb elevation is a common feature under neurodegenerative conditions, including Alzheimer's disease, aging, and ischemic injury. We...

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Ubiquitin (Ub), a central regulator of protein turnover, can be phosphorylated by PINK1 (PTEN-induced putative kinase 1) to generate S65-phosphorylated ubiquitin (pUb). Elevated pUb levels have been observed in aged human brains and in Parkinson's disease, but the mechanistic link between pUb elevation and neurodegeneration remains unclear. Here, we demonstrate that pUb elevation is a common feature under neurodegenerative conditions, including Alzheimer's disease, aging, and ischemic injury. We...

CONCLUSIONS: The study highlights that RAC is not only structured by formal policies but also co-created through everyday interactions among residents and staff. While previous research has emphasised the need for staff training and inclusive policies, these findings suggest that education alone may not be sufficient. This study argues that there may be value in establishing dedicated residential care facilities that are explicitly LGBTQ-friendly.

cTAGE5/MEA6 plays a pivotal role in COPII complex assembly, ER-to-Golgi trafficking, and secretion. However, whether cTAGE5/MEA6 is involved in other cellular functions remains unclear. Here, we show that conditional cTAGE5 knockout results in embryonic lethality during development and premature aging in adult mice. cTAGE5 deficiency leads to abnormal nuclear structure and disturbed cell proliferation in MEF cells. Further mechanistic studies reveal that cTAGE5 localizes not only to the ER exit...

CONCLUSION: Lower baseline hippocampal z-scores are associated with a greater rate of hippocampal atrophy to the follow-up examination. If validated in larger cohorts, these findings could help establish cut-off values for pathological atrophy in cross-sectional studies.

INTRODUCTION: Conventional machine learning (ML) approaches for constructing biological age (BA) have predominantly relied on blood-based markers, limiting their scope. This study aims to develop and validate novel ML-based BA models using a comprehensive set of clinical, behavioral, and socioeconomic factors and evaluate their predictive performance for mortality.