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Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder, defined pathologically by the accumulation of Aβ plaques and Tau neurofibrillary tangles, accompanied by widespread metabolic dysregulation. Recently, "metabolic reprogramming (MetR)", referring to the dynamic adaptation of cellular metabolic networks in response to environmental or functional demands, has emerged as a novel conceptual perspective for understanding AD. In the context of AD, the dysregulation of MetR is...

The leukodystrophy Pelizaeus-Merzbacher disease (PMD) is caused by myelin protein proteolipid protein gene (PLP1) mutations. PMD is characterized by oligodendrocyte death and CNS hypomyelination; thus, increasing oligodendrocyte survival and enhancing myelination could provide therapeutic benefit. Here, we use the PMD mouse model Jimpy to determine the impact of the integrated stress response (ISR) on the oligodendrocyte response to mutant PLP expression. Male Jimpy animals in which the...

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Real or simulated microgravity induces a senescence-like modification of carotid artery in both human and animal observations, with the mechanisms not fully elucidated. Here, we aim to elucidate the role of sterol regulatory element-binding protein 1 (SREBP1, encoded by Srebf1) mediated lipogenesis in the process. Pharmacological activation of SREBP1 directly triggers senescence-like transformation in vascular smooth muscle cells (VSMC), while silencing Srebf1 exerts an opposite effect....

Difficult-to-treat rheumatoid arthritis (D2T RA) is an emerging challenge in aging populations, where disease persistence and therapeutic failure often reflect not only autoimmune dysregulation but also the cumulative effects of age-related biological changes across multiple organ systems. This review reframes D2T RA through the lens of geroscience, highlighting how immunosenescence, inflammaging, and organ system vulnerability converge to create a treatment-resistant disease phenotype....

BACKGROUND: Plant-based diets are increasingly adopted. Plant-based foods exhibit a lower protein quantity and quality compared to animal-based foods. As such, a fully plant-based, i.e. vegan, diet may be suboptimal for the maintenance of skeletal muscle mass later in life. The primary objectives of this study protocol are therefore: (1) To assess the effect of a 12-week self-composed vegan diet in comparison to an omnivorous diet on thigh muscle volume in community-dwelling older adults; and...

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...

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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.