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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...

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...

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...

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.

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...

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...

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.

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.

Science, Volume 386, Issue 6725, November 2024.

Science, Volume 386, Issue 6725, November 2024.