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Relationship between macronutrients and energy intake and liver serum transaminase levels in elderly athletes and non-athletes: findings from the Neyshabur longitudinal study on aging
CONCLUSIONS: This study revealed that higher calorie, protein, and carbohydrate intake were associated with elevated ALT and AST levels in elderly individuals, particularly athletes. For athletes, all three nutrients were linked to elevated ALT, while only carbohydrates and calories impacted AST. For non-athletes, only protein affected ALT. These findings suggest that tailored nutritional strategies may be necessary to preserve liver health in active aging populations.
The ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model
Recent studies indicated that the dysregulation of mitochondria-associated endoplasmic reticulum membrane (MAM) could be a significant hub in the pathogenesis of Parkinson's disease (PD). However, little has been known about how MAM altered in PD. This study was aimed to observe morphological changes and analyze proteomic profiles of MAM in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. In MPTP-treated mice, transmission electron microscopy was applied for MAM...
Restoration of hair follicle inductive properties by depletion of senescent cells
Senescent cells secrete a senescence-associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded in vitro, and rapidly accumulate senescent cells in culture. Protein and RNA-seq analysis revealed an accumulation of DP-specific SASP factors including IL-6, IL-8, MCP-1, and TIMP-2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells,...
An overview of the genes and biomarkers in Alzheimer's disease
Alzheimer's disease (AD) is the most common type of dementia and neurodegenerative disease characterized by neurofibrillary tangles (NFTs) and amyloid plaque. Familial AD is caused by mutations in the APP, PSEN1, and PSEN2 genes and these mutations result in the early onset of the disease. Sporadic AD usually affects older adults over the age of 65 years and is, therefore classified as late-onset AD (LOAD). Several risk factors associated with LOAD including the APOE gene have been identified....
Transcranial optogenetic brain modulator for precise bimodal neuromodulation in multiple brain regions
Transcranial brain stimulation is a promising technology for safe modulation of brain function without invasive procedures. Recent advances in transcranial optogenetic techniques with external light sources, using upconversion particles and highly sensitive opsins, have shown promise for precise neuromodulation with improved spatial resolution in deeper brain regions. However, these methods have not yet been used to selectively excite or inhibit specific neural populations in multiple brain...
Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits
Rare mutations in the gene encoding presenilin2 (PSEN2) are known to cause familial Alzheimer's disease (FAD). Here, we explored how altered PSEN2 expression impacts on the amyloidosis, endolysosomal abnormalities, and synaptic dysfunction observed in female APP knock-in mice. We demonstrate that PSEN2 knockout (KO) as well as the FAD-associated N141IKI mutant accelerate AD-related pathologies in female mice. Both models showed significant deficits in working memory that linked to elevated PSEN2...
Lifespan longitudinal changes in mesocortical thickness and executive function: Role of dopaminergic genetic predisposition
Dopamine (DA) signaling is critical for optimal cognitive aging, especially in prefrontal-parietal and fronto-striatal networks. Single nucleotide polymorphisms associated with dopamine regulation, COMTVal158Met and DRD2C957T, stand to exert influence on executive function performance via neural properties. The current study investigated whether longitudinal thinning of mesocortical regions is related to COMT and DRD2 genetic predisposition and associated with decline in executive function over...
An integrated single-cell atlas of blood immune cells in aging
Recent advances in single-cell technologies have facilitated studies on age-related alterations in the immune system. However, previous studies have often employed different marker genes to annotate immune cell populations, making it challenging to compare results. In this study, we combined seven single-cell transcriptomic datasets, comprising more than a million cells from one hundred and three donors, to create a unified atlas of human peripheral blood mononuclear cells (PBMC) from both young...
Telomere function and regulation from mouse models to human ageing and disease
Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death. Telomere shortening occurs with ageing and may contribute to associated maladies such as infertility, neurodegeneration, cancer, lung dysfunction and haematopoiesis disorders. Telomere dysfunction (sometimes without...
Effect of transcranial direct current stimulation with cognitive training on executive functions in healthy older adults: a secondary analysis from the ACT trial
Cognitive aging has become a public health concern as the mean age of the population is ever-increasing. It is a naturalistic and common process of degenerative and compensatory changes that may result in neurocognitive disorders. While heterogeneous, cognitive aging mostly affects executive functions that may be associated with functional losses during activities of daily living. Cognition-oriented treatments like cognitive training and transcranial direct current stimulation (tDCS) have...
Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer's disease
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by extracellular amyloid plaques and neuronal Tau tangles. A recent study found that the APOE3 Christchurch (APOECh) variant could delay AD progression. However, the underlying mechanisms remain unclear. In this study, we established neuron-microglia co-cultures and neuroimmune organoids using isogenic APOE3 and APOECh microglia derived from human induced pluripotent stem cells (hiPSCs) with PSEN1 mutant...
Age-Related Trajectories of Health Decline Among Immigrants and Natives in Europe: The Effect of Education
Background: The ability to age healthily is highly dependent on individual characteristics that include gender, social class, a range of biological and contextual factors, and migrant background. Indeed, immigration has changed the demographic composition and social structure of many European countries, generating an increasing interest in how societies, and immigrants in particular, are aging. Research Design: This paper compares the age-related trajectories of health decline in three health...
A mutation in DNA polymerase gamma harbours a shortened lifespan and high sensitivity to mutagens in the filamentous fungus Neurospora crassa
Hyphal elongation is the vegetative growth of filamentous fungi, and many species continuously elongate their hyphal tips over long periods. The details of the mechanisms for maintaining continuous growth are not yet clear. A novel short lifespan mutant of N. crassa that ceases hyphal elongation early was screened and analyzed to better understand the mechanisms for maintaining hyphal elongation in filamentous fungi. The mutant strain also exhibited high sensitivity to mutagens such as...
Gut microbiota and epigenetic age acceleration: a bi-directional Mendelian randomization study
CONCLUSION: Our study implicates the potential causal effects of specific microbiota on EAA, potentially providing novel insights into the prevention aging through specific gut microbiota.
Integrative pathway analysis across humans and 3D cellular models identifies the p38 MAPK-MK2 axis as a therapeutic target for Alzheimer's disease
Alzheimer's disease (AD) presents a complex pathological landscape, posing challenges to current therapeutic strategies that primarily target amyloid-β (Aβ). Using a novel integrative pathway activity analysis (IPAA), we identified 83 dysregulated pathways common between both post-mortem AD brains and three-dimensional AD cellular models showing robust Aβ42 accumulation. p38 mitogen-activated protein kinase (MAPK) was the most upregulated common pathway. Active p38 MAPK levels increased in the...
Piezo1 exacerbates inflammation-induced cartilaginous endplate degeneration by activating mitochondrial fission via the Ca<sup>2+</sup>/CaMKII/Drp1 axis
Mitochondrial homeostasis plays a crucial role in degenerative joint diseases, including cartilaginous endplate (CEP) degeneration. To date, research into mitochondrial dynamics in IVDD is at an early stage. Since Piezo1 is a novel Ca^(2+)-permeable channel, we asked whether Piezo1 could modulate mitochondrial fission through Ca^(2+) signalling during CEP degeneration. In vitro and in vivo models of inflammation-induced CEP degeneration were established with lipopolysaccharide (LPS). We found...
The role of serum α-Klotho levels in preventing hearing impairment among middle-aged and older adults: insights from a nationally representative sample
CONCLUSION: This study provided novel evidence of a negative association between serum α-Klotho and hearing impairment in adults aged 40-69. Our results suggested a protective role of serum α-Klotho on adults with hearing loss.
Trajectories of cognitive function and frailty in older adults in China: a longitudinal study
CONCLUSION: Our findings suggest a co-development pattern between cognitive function and frailty in Chinese older adults aged 55 years and above. While cognitive impairment may be irreversible, frailty is a condition that can be potentially reversed. Early detecting is crucial in preventing cognitive decline, considering the shared trajectory of these conditions.