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Disease-associated microglia in neurodegenerative diseases: Friend or foe?

1 month 1 week ago
Recent advances in single-cell transcriptomics have led to the identification of disease-associated microglia (DAM) as a distinct, conserved microglia state associated with mouse models of Alzheimer's disease (AD) and amyotrophic lateral sclerosis, and with aging. DAM are characterized by downregulation of homeostatic genes and upregulation of lipid metabolism and phagocytosis genes, including key risk factors for AD in humans. Although characterized in models of AD, whether DAM acts as...
Yi-Hsuan Cheng

A paradoxical role of autophagy: promoting protein aggregates and hindering rejuvenation in a Caenorhabditis elegans L1 arrest model

1 month 1 week ago
Macroautophagy (hereafter referred to as autophagy) is widely recognized as a central pathway for the clearance of protein aggregates and the maintenance of proteostasis. However, a recent study by Murley et al. challenges this conventional view. Using a Caenorhabditis elegans L1 arrest aging model, the authors found that autophagy activation impedes rejuvenation by promoting the accumulation of intra- 10 lysosomal protein aggregates and inducing lysosomal membrane damage. This unexpected...
Yuxiang Huang

Single-Cell RNA Sequencing Identifies Accumulation of Fcgr2b + Virtual Memory-Like CD8 T Cells With Cytotoxic and Inflammatory Potential in Aged Mouse White Adipose Tissue

1 month 1 week ago
Aging and obesity are associated with pro-inflammatory changes in adipose tissue. Overlapping mechanisms, such as the infiltration of inflammatory macrophages and T cells into visceral adipose tissue, have been implicated in contributing to inflammation. However, a comparative analysis of both states is needed to identify distinct regulatory targets. Here, we performed single-cell RNA sequencing of stromal vascular fractions (SVF) isolated from gonadal white adipose tissue (gWAT) of young mice...
Archit Kumar

An Ad Libitum-Fed Diet That Matches the Beneficial Lifespan Effects of Caloric Restriction but Acts via Opposite Effects on the Energy-Splicing Axis

1 month 1 week ago
Caloric restriction (CR) with fasting extends lifespan but is difficult to maintain in humans. Here, we compared conventional CR with periods of fasting to an ad libitum-fed low-protein, high-carbohydrate (LPHC) diet diluted 25% with non-digestible fibre. Both approaches similarly enhanced longevity and metabolic health in mice relative to a control diet. Proteomic analysis of liver tissue revealed that CR increased proteins associated with energy and mitochondrial pathways. By contrast, the...
Amanda E Brandon

The Metabolic Transition Between Fasting and Feeding Alters Aging-Associated Metabolites, Lowers BCAAs, and Stimulates FGF21 Production in Humans

1 month 1 week ago
Fasting-based interventions are gaining momentum as strategies to modulate longevity. Conversely, the same metabolic adaptations that once ensured survival during starvation now contribute to the global obesity epidemic. While previous studies have characterized metabolic changes during fasting, few have examined the refeeding phase, and most lack an integrated analysis of key hormonal and metabolic regulators, including insulin, leptin, adiponectin, free T3, FGF21, and the plasma metabolome. To...
Maria Lastra Cagigas

Obstructive sleep apnea and aging of the cardiovascular system: a multidimensional analysis of the mechanisms involved

1 month 1 week ago
Emerging evidence has revealed a strong association between obstructive sleep apnea (OSA) and aging. Considering the critical role of the cardiovascular system, this review explores the key mechanisms linking OSA to cardiovascular aging through a focus on chronic intermittent hypoxia (CIH) -induced oxidative stress and chronic inflammation. Specifically, we examine six key pathways: (1) cellular senescence, (2) mitochondrial dysfunction, (3) metabolic dysregulation, (4) telomere attrition, (5)...
Xiaolin Hao