Aging & Longevity

Non-coding RNAs as regulators of autophagy in chondrocytes: Mechanisms and implications for osteoarthritis

2 weeks 1 day ago
Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs...
Chenyu Zhu

Hierarchically porous and single Zn atom-embedded carbon molecular sieves for H<sub>2</sub> separations

2 weeks 1 day ago
Hierarchically porous materials containing sub-nm ultramicropores with molecular sieving abilities and microcavities with high gas diffusivity may realize energy-efficient membranes for gas separations. However, rationally designing and constructing such pores into large-area membranes enabling efficient H(2) separations remains challenging. Here, we report the synthesis and utilization of hybrid carbon molecular sieve membranes with well-controlled nano- and micro-pores and single zinc atoms...
Leiqing Hu

A tandem activity-based sensing and labeling strategy reveals antioxidant response element regulation of labile iron pools

2 weeks 2 days ago
Iron is an essential element for life owing to its ability to participate in a diverse array of oxidation-reduction reactions. However, misregulation of iron-dependent redox cycling can also produce oxidative stress, contributing to cell growth, proliferation, and death pathways underlying aging, cancer, neurodegeneration, and metabolic diseases. Fluorescent probes that selectively monitor loosely bound Fe(II) ions, termed the labile iron pool, are potentially powerful tools for studies of this...
Aidan T Pezacki

Mitogen signaling strength and duration can control cell cycle decisions

2 weeks 2 days ago
Decades ago, mitogen-promoted signaling duration and strength were observed to be sensed by the cell and to be critical for its decisions: to proliferate or differentiate. Landmark publications established the importance of mitogen signaling not only in the G(1) cell cycle phase but also through the S and the G(2)/M transition. Despite these early milestones, how mitogen signal duration and strength, short and strong or weaker and sustained, control cell fate has been largely unheeded. Here, we...
Ruth Nussinov

Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes

2 weeks 3 days ago
Mature red blood cells (RBCs) lack mitochondria and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging in vivo or storage in blood banks. Here, we leveraged 13,029 volunteers from the Recipient Epidemiology and Donor Evaluation Study to identify associations between end-of-storage levels of glycolytic metabolites and donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding phosphofructokinase 1, platelet (detected in mature RBCs);...
Travis Nemkov

Prohibitins, Phb1 and Phb2, function as Atg8 receptors to support yeast mitophagy and also play a negative regulatory role in Atg32 processing

2 weeks 3 days ago
The prohibitins Phb1 and Phb2 assemble at the mitochondrial inner membrane to form a multi-dimeric complex. These scaffold proteins are highly conserved in eukaryotic cells, from yeast to mammals, and have been implicated in a variety of mitochondrial functions including aging, proliferation, and degenerative and metabolic diseases. In mammals, PHB2 regulates PINK1-PRKN mediated mitophagy by interacting with lipidated MAP1LC3B/LC3B. Despite their high conservation, prohibitins have not been...
Diana García-Chávez

Developing transcriptomic signatures as a biomarker of cellular senescence

2 weeks 3 days ago
Cellular senescence is a cell fate driven by different types of stress, where damaged cells exit from the cell cycle and, in many cases, develop an inflammatory senescence-associated secretory phenotype (SASP). Senescence has often been linked to driving aging and the onset of multiple diseases conferred by the harmful SASP, which disrupts tissue homeostasis and impairs the regular function of many tissues. This phenomenon was first observed in vitro when fibroblasts halted replication after...
Shamsed Mahmud

Enhancing neuronal reticulophagy: a strategy for combating aging and APP toxicity

2 weeks 3 days ago
Reticulophagy, which directs the endoplasmic reticulum (ER) to the phagophore for sequestration within an autophagosome and subsequent lysosomal degradation via specific receptors, is essential for ER quality control and is implicated in various diseases. This study utilizes Drosophila to establish an in vivo model for reticulophagy. Starvation-induced reticulophagy is detected across multiple tissues in Drosophila. Whole-body upregulation or downregulation of the expression of reticulophagy...
Wenqing Mou

FOXO-regulated DEAF1 controls muscle regeneration through autophagy

2 weeks 3 days ago
The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a...
Kah Yong Goh

Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice

2 weeks 3 days ago
Frailty is a geriatric, multi-dimensional syndrome that reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead and represents a risk factor for the development of Alzheimer's disease (AD). The fact that frailty is recognized as a reversible condition encourages the identification of earlier biomarkers to timely predict and prevent its...
Letizia Dacomo

Cardiac and skeletal muscle manifestations in the G608G mouse model of Hutchinson-Gilford progeria syndrome

2 weeks 3 days ago
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder resulting from de novo mutations in the lamin A gene. Children with HGPS typically pass away in their teenage years due to cardiovascular diseases such as atherosclerosis, myocardial infarction, heart failure, and stroke. In this study, we characterized the G608G HGPS mouse model and explored cardiac and skeletal muscle function, along with senescence-associated phenotypes in fibroblasts. Homozygous G608G HGPS mice...
Yeojin Hong

Targeting specific DNA G-quadruplexes with CRISPR-guided G-quadruplex-binding proteins and ligands

2 weeks 4 days ago
Despite the demonstrated importance of DNA G-quadruplexes (G4s) in health and disease, technologies to readily manipulate specific G4 folding for functional analysis and therapeutic purposes are lacking. Here we employ G4-stabilizing protein/ligand in conjunction with CRISPR to selectively facilitate single or multiple targeted G4 folding within specific genomic loci. We demonstrate that fusion of nucleolin with a catalytically inactive Cas9 can specifically stabilize G4s in the promoter of...
Geng Qin

Thermal facial image analyses reveal quantitative hallmarks of aging and metabolic diseases

2 weeks 4 days ago
Although human core body temperature is known to decrease with age, the age dependency of facial temperature and its potential to indicate aging rate or aging-related diseases remains uncertain. Here, we collected thermal facial images of 2,811 Han Chinese individuals 20-90 years old, developed the ThermoFace method to automatically process and analyze images, and then generated thermal age and disease prediction models. The ThermoFace deep learning model for thermal facial age has a mean...
Zhengqing Yu

The germline coordinates mitokine signaling

2 weeks 4 days ago
The ability of mitochondria to coordinate stress responses across tissues is critical for health. In C. elegans, neurons experiencing mitochondrial stress elicit an inter-tissue signaling pathway through the release of mitokine signals, such as serotonin or the Wnt ligand EGL-20, which activate the mitochondrial unfolded protein response (UPR^(MT)) in the periphery to promote organismal health and lifespan. We find that germline mitochondria play a surprising role in neuron-to-periphery UPR^(MT)...
Koning Shen

The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening

2 weeks 4 days ago
A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity...
Ralph Patrick

Mechanism and therapeutic targets of the involvement of a novel lysosomal proton channel TMEM175 in Parkinson's disease

2 weeks 4 days ago
Parkinson's disease (PD), recognized as the second most prevalent neurodegenerative disease in the aging population, presents a significant challenge due to the current lack of effective treatment methods to mitigate its progression. Many pathogenesis of PD are related to lysosomal dysfunction. Moreover, extensive genetic studies have shown a significant correlation between the lysosomal membrane protein TMEM175 and the risk of developing PD. Building on this discovery, TMEM175 has been...
Tingting Feng

Rockfish: A transformer-based model for accurate 5-methylcytosine prediction from nanopore sequencing

2 weeks 4 days ago
DNA methylation plays an important role in various biological processes, including cell differentiation, ageing, and cancer development. The most important methylation in mammals is 5-methylcytosine mostly occurring in the context of CpG dinucleotides. Sequencing methods such as whole-genome bisulfite sequencing successfully detect 5-methylcytosine DNA modifications. However, they suffer from the serious drawbacks of short read lengths and might introduce an amplification bias. Here we present...
Dominik Stanojević

O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer

2 weeks 4 days ago
Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc...
Yi Zhang
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