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Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research

5 months 1 week ago
The recent, controversial approval of antibody-based treatments for Alzheimer's disease (AD) is fueling a heated debate on the molecular determinants of this condition. The discussion should also incorporate a critical revision of the limitations of preclinical mouse models in advancing our understanding of AD. We critically discuss the limitations of animal models, stressing the need for careful consideration of how experiments are designed and results interpreted. We identify the shortcomings...
Alberto Granzotto

Poly ADP-ribose signaling is dysregulated in Huntington disease

5 months 1 week ago
Huntington disease (HD) is a genetic neurodegenerative disease caused by cytosine, adenine, guanine (CAG) expansion in the Huntingtin (HTT) gene, translating to an expanded polyglutamine tract in the HTT protein. Age at disease onset correlates to CAG repeat length but varies by decades between individuals with identical repeat lengths. Genome-wide association studies link HD modification to DNA repair and mitochondrial health pathways. Clinical studies show elevated DNA damage in HD, even at...
Tamara Maiuri

A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency

5 months 1 week ago
Science, Volume 385, Issue 6716, September 2024.
Qiuhe Lu, Thomas C. A. Hitch, Julie Y. Zhou, Mohammed Dwidar, Naseer Sangwan, Dylan Lawrence, Lila S. Nolan, Scott T. Espenschied, Kevin P. Newhall, Yi Han, Paul E. Karell, Vanessa Salazar, Megan T. Baldridge, Thomas Clavel, Thaddeus S. Stappenbeck





Temperature-dependent lifespan extension is achieved in miR-80-deleted Caenorhabditis elegans by NLP-45 to modulate endoplasmic reticulum unfolded protein responses

5 months 2 weeks ago
MicroRNA plays a crucial role in post-transcriptional gene regulation and has recently emerged as a factor linked to aging, but the underlying regulatory mechanisms remain incompletely understood. In this study, we observed lifespan-extending effects in miR-80-deficient Caenorhabditis elegans at 20°C but not 25°C. At 20°C, miR-80 deletion leads to NLP-45 upregulation, which positively correlates to increased abu transcripts and extended lifespan. Supportively, we identified miR-80 binding...
Chunlin Zhao

Tissue-specific functions of MSCs are linked to homeostatic muscle maintenance and alter with aging

5 months 2 weeks ago
Mesenchymal stromal cells (MSCs), also known as fibro-adipogenic progenitors, play a critical role in muscle maintenance and sarcopenia development. Although analogous MSCs are present in various tissues, recent single-cell RNA-seq studies have revealed the inter-tissue heterogeneity of MSCs. However, the functional significance of MSC heterogeneity and its role in aging remain unclear. Here, we investigated the properties of MSCs and their age-related changes in seven mouse tissues through...
Tamaki Kurosawa

Quality control of mitochondria involves lysosomes in multiple definitive ways

5 months 2 weeks ago
Mitochondria are crucial organelles in maintaining cellular homeostasis. They are involved in processes such as energy production, metabolism of lipids and glucose, and cell death regulation. Mitochondrial dysfunction can lead to various health issues such as aging, cancer, neurodegenerative diseases, and chronic liver diseases. While mitophagy is the main process for getting rid of excess or damaged mitochondria, there are additional mechanisms for preserving mitochondrial quality. One such...
Xiaowen Ma