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CONCLUSION: Effective fall prevention in Saudi Arabia requires culturally sensitive, system-wide strategies that address both structural constraints and individual-level beliefs. By enhancing interdisciplinary coordination, improving education, and prioritizing patient-centered approaches, healthcare systems can better support safe aging and reduce fall-related risks among older adults.

Cystathionine γ-lyase (CSE), the enzyme responsible for neuronal cysteine and hydrogen sulfide production, is dysregulated in aging and neurodegenerative diseases including Alzheimer's disease and Huntington's disease, both marked by cognitive decline in addition to motor deficits. To determine whether CSE loss directly causes cognitive decline, we genetically ablated CSE in mice. This loss was sufficient to induce oxidative damage, compromise blood-brain barrier integrity, impair neurogenesis...

Cystathionine γ-lyase (CSE), the enzyme responsible for neuronal cysteine and hydrogen sulfide production, is dysregulated in aging and neurodegenerative diseases including Alzheimer's disease and Huntington's disease, both marked by cognitive decline in addition to motor deficits. To determine whether CSE loss directly causes cognitive decline, we genetically ablated CSE in mice. This loss was sufficient to induce oxidative damage, compromise blood-brain barrier integrity, impair neurogenesis...

The bidirectional non-linear communication between blood pressure (BP) and heartbeat is critical to cardiovascular homeostasis, which remains poorly understood, especially under hypertensive conditions. We implemented transfer entropy (TE), an information-theoretic measure of directional coupling, to characterize such bidirectional coupling between BP and heartbeat and its relationships to arterial stiffness and walking performance in older adults. A total of 493 older adults (201 normotensive...

Individuals with knee osteoarthritis (KOA) have skeletal muscle changes around the knee joint including reduced quadricep muscle mass and increased intermuscular adipose tissue (IMAT). We examined the cellular composition and transcriptional profiles using single-nuclei RNA sequencing in IMAT from 6 older women with KOA and knee pain and 5 older women without KOA or knee pain from the Study of Muscle, Mobility and Aging (SOMMA). From the resulting 21,436 nuclei, we identified 6 major cell types...

Mitochondrial dysfunction is widely recognized as a key driver of aging and neurodegenerative diseases, with mitophagy acting as an essential cellular mechanism for the selective clearance of damaged mitochondria. While pharmacological activation of mitophagy has been reported to exert beneficial effects across multiple neurodegenerative diseases, its functional relevance in amyotrophic lateral sclerosis (ALS) remains poorly characterized. Our recent study published in EMBO Molecular Medicine...

From ancient humans to modern woes, these are the stories that stuck with our News editors this year

A marked evolution in Alzheimer's disease (AD) therapy research is ongoing. In this perspective, we highlight emerging outcomes of tau-targeting approaches with disease-modifying potential evidenced by PET-based slowing of tau accumulation and early signs of cognitive benefit. We outline how decades of iterative amyloid β (Aβ)-trial refinement leading to the recent successes of approved anti-Aβ therapies have set the stage for accelerated optimization of next-generation trials. We summarize key...

Emerging neuroimaging evidence has propelled the formulation of the hypothesis that freezing of gait (FOG) in Parkinson's disease (PD) arises from dysfunction within the locomotor network. However, to date, there has been a lack of functional connectivity analyses targeting the hyperdirect pathway (HDP) to explore this hypothesis. In this study, we investigate impaired communication within the HDP neural circuitry in FOG patients. Fifty-nine PD patients (33 PD-nFOG and 26 PD-FOG) and thirty...

CONCLUSIONS: Older adults have a compartmentalized understanding of brain health, often accompanied by misconceptions and tend to hold negative attitudes toward brain health promotion, highlighting an urgent need for professional guidance to provide correct education and direction. Our study reveals that effective brain health promotion requires enhancing internal motivation, building external support networks, and overcoming implementation barriers through integrated strategies, while crucially...

Surfactant proteins, particularly SP-A and SP-D, S100 family members and fibronectin belong to the group of so-called stress-related molecules and share the characteristic of being expressed at anatomical barriers such as the skin, pulmonary/respiratory epithelia, and the intestinal tract. In this context, they constitute part of the body's first line of defence, acting in concert with immune cells to counter a broad spectrum of external and internal stressors (exposomes), potentially fuelling...

Biological aging varies between individuals and may be influenced by health behaviors. Using data from 45,438 UK Biobank participants, we found that a higher proteomic aging score (ProtAgeGap) was linked to lower physical activity and increased risk of type 2 diabetes. The UK Biobank cohort included both men and women. In a 12-week supervised exercise study (MyoGlu) in 26 men, ProtAgeGap decreased by the equivalent of 10 months. While most of the 204 proteins in the score remained stable, some,...

CONCLUSION: The prevalence of LTBI among individuals aged 65 and above in the relatively confined rural areas of Zhejiang Province was as high as 26.78%, which required focused attention with the intensification of population aging. Male sex, smoking duration, and exercise frequency were all associated with LTBI, and the underlying mechanisms needed to be explored in the future. The domestic reagent AIMTB of China showed good agreement with IGRA reagents in old adults, which offered a model for...

BACKGROUND: Accumulating evidence demonstrated that the cerebellum contributes to a wide range of sensorimotor and cognitive functions. However, the relationship between cerebellar function and cognitive abilities in normal aging populations remains unclear.

CONCLUSIONS: The GFBS is a reliable and effective tool for assessing the level of burden among older adults in China. It consists of three dimensions: economic and social burden, personal emotional burden, and social interaction burden. Among older adults, females, widowed individuals, those with chronic illnesses, those lacking a fixed income, and those in poor health experience a higher level of feelings of being a burden.

CONCLUSION: In conclusion, this study provides evidence that Apremilast may exert protective effects against Aβ-induced cytotoxicity in BV2 and HT-22 cells by modulating the PI3K/Akt signaling pathway. However, further validation of its dosage and efficacy in vivo is required.

α-Synuclein (α-syn) fibrils accumulate in Parkinson's disease, spreading between cells to template misfolding and drive neurodegeneration. α-Syn fibril entry into healthy neurons is a key step. Here, we comprehensively assessed the membrane proteome for α-syn fibril binding. We identified mGluR4 and NPDC1 as nigral surface proteins binding and internalizing α-syn fibrils. While striatal α-syn fibril injection led to nigral dopamine neuron loss in wild type mice, deletion of either Grm4 or Npdc1...

Alzheimer's disease (AD) is a major public health concern in societies with increasingly ageing populations. Accumulating evidence implies a specific link between the development of tauopathy, cognitive impairment, and sleep loss in AD patients. P301S mutant tau-transgenic (PS19) mice, modelling frontotemporal dementia (FTD) and AD tauopathy, demonstrate sleep loss and cognitive impairment. We aimed to assess the progression of sleep loss and cognitive decline longitudinally in both sexes of...

Neuromuscular transmission plays a crucial role in muscle function, with differences in neurotransmitter release potentially influenced by sex and aging. While hormonal effects on neurotransmission have been studied, their impact on acetylcholine (ACh) release at the neuromuscular junction remains largely unexplored. Understanding these differences could provide insights into age-related muscle function decline and sex-specific variations in neuromuscular disorders. This study aims to...

Myeloid-derived suppressor cells (MDSCs) are recognized as a key mediator of immunosuppression in aging, which induce immunosenescence and increase elderly people's susceptibility to infections, cancers, autoimmune diseases, and degenerative diseases. However, the commonly used MDSC markers overlap with those defining healthy and normal neutrophils or monocytes, which makes it challenging to distinguish MDSCs from their myeloid counterparts, and hampers deeper understanding of the...