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Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (e.g., senescence plasmids) by effecting a form of cytolytic cell death. However, the underlying mechanisms by which RCD-1 acts on the cell membrane remain elusive. Here, we demonstrate that RCD-1 binds...

The onset and development of Alzheimer's disease is linked to the accumulation of pathological aggregates formed from the normally monomeric amyloid-β peptide within the central nervous system. These Aβ aggregates are increasingly successfully targeted with clinical therapies at later stages of the disease, but the fundamental molecular steps in early stage disease that trigger the initial nucleation event leading to the conversion of monomeric Aβ peptide into pathological aggregates remain...

Sarcopenia and cancer cachexia are two life-threatening conditions often misdiagnosed. The skeletal muscle is one of the organs most adversely affected by these conditions, culminating in poor quality of life and premature mortality. In addition, it has been suggested that chemotherapeutic agents exacerbate cancer cachexia, as is the case of doxorubicin. Herein, we sought to investigate markers of inflammation and neuromuscular junction (NMJ) remodeling during aging and in response to cancer or...

Benign prostatic hyperplasia (BPH), characterized as a chronic disease with unregulated enlargement of prostatic gland, is commonly observed in elderly men leading to lower urinary tract dysfunction. Sestrin2 plays a role in the maintenance of cellular homeostasis and protects organisms from various stimuli. The exact role of Sestrin2 in the etiology of BPH, a common age-related disease, remains unknown. Here, we explored the regulatory function of Sestrin2 in modulating autophagy and its...

The nematode C. elegans has long served as a gold-standard model organism in aging research, particularly since the discovery of long-lived mutants in conserved aging pathways including daf-2 (IGF1) and age-1 (PI3K). Its short lifespan and small size make it highly suitable for high-throughput experiments. While numerous molecules have been tested for their effects on C. elegans lifespan, consensus is still lacking regarding the most effective and reproducible compounds. Confounding effects,...

The developmental theory of ageing proposes that age-specific decline in the force of natural selection results in suboptimal levels of gene expression in adulthood, leading to functional senescence. This theory explicitly predicts that optimising gene expression in adulthood can ameliorate functional senescence and improve fitness. Reduced insulin/IGF-1 signalling (rIIS) extends the reproductive lifespan of Caenorhabditis elegans at the cost of reduced reproduction. Here, we show that...

Ribosomal RNA is the main component of the ribosome, which is essential for protein synthesis. The diploid human genome contains several hundred copies of the rDNA transcription unit (TU). Droplet digital PCR and deep bisulfite sequencing were used to determine the absolute copy number (CN) and the methylation status of individual rDNA TU in blood samples of healthy individuals. The absolute CN ranged from 243 to 895 (median 469). There was no difference in absolute CN between males and females...

In this study, we investigated age-related changes in clinical laboratory data and their association with mortality in dogs from the Golden Retriever Lifetime Study. By analyzing complete blood count (CBC) and biochemistry data from 2'412 Golden Retrievers over 16,678 visits, we observed significant changes during the first 2 years of life and throughout aging. Based on these observations, we developed a biological aging clock using a LASSO model to predict age based on blood markers, achieving...

The question of what mechanisms maintain tropical biodiversity is a critical frontier in ecology, intensified by the heightened risk of biodiversity loss faced in tropical regions. Ecological theory has shed light on multiple mechanisms that could lead to the high levels of biodiversity in tropical forests. But variation in species abundances over time may be just as important as overall biodiversity, with a more immediate connection to the risk of extirpation and biodiversity loss. Despite the...

Joining heterogeneous materials in engineered structures remains a significant challenge due to stress concentration at interfaces, which often leads to unexpected failures. Investigating the complex, multiscale-graded structures found in animal tissue provides valuable insights that can help address this challenge. The human meniscus root-bone interface is an exemplary model, renowned for its exceptional fatigue resistance, toughness, and interfacial adhesion properties throughout its lifespan....

CONCLUSION: Indoor ventilation frequency is related to depressive symptoms in older persons. Communities and families should pay more attention to indoor ventilation and intervene in time to promote and improve the mental health of older persons.

Science, Volume 387, Issue 6732, January 2025.

Science, Volume 387, Issue 6732, January 2025.

Science, Volume 387, Issue 6732, January 2025.

Science, Volume 387, Issue 6732, January 2025.

Science, Volume 387, Issue 6732, January 2025.