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Aβ-driven nuclear pore complex dysfunction alters activation of necroptosis proteins in a mouse model of Alzheimer's disease

1 week 2 days ago
The emergence of Aβ pathology is one of the hallmarks of Alzheimer's disease (AD), but the mechanisms and impact of Aβ in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope; its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of Aβ on NPC...
Vibhavari Aysha Bansal

BRD4/MAP2K7/PGF Signaling Axis Promotes Senescence and Extracellular Matrix Metabolism of Nucleus Pulposus Cells in Intervertebral Disk Degeneration

1 week 2 days ago
Intervertebral disk degeneration (IDD) is a common age-related degenerative disease of the spine that imposes a substantial economic burden on both families and society. Despite substantial advances in understanding the mechanisms underlying IDD, effective therapeutic interventions for its treatment and prevention remain elusive. Our previous study identified a positive correlation between IDD severity and bromodomain-containing protein 4 (BRD4) expression. However, the multifaceted role of BRD4...
Guangzhi Zhang

Knowing the enemy: strategic targeting of complement to treat Alzheimer disease

1 week 2 days ago
The complement system protects against infection, positively responds to tissue damage, clears cell debris, directs and modulates the adaptive immune system, and functions in neuronal development, normal synapse elimination and intracellular metabolism. However, complement also has a role in aberrant synaptic pruning and neuroinflammation - processes that lead to a feedforward loop of inflammation, injury and neuronal death that can contribute to neurodegenerative and neurological disorders,...
Andrea J Tenner

High-content screening identifies ganoderic acid A as a senotherapeutic to prevent cellular senescence and extend healthspan in preclinical models

1 week 2 days ago
Accumulated senescent cells during the aging process are a key driver of functional decline and age-related disorders. Here, we identify ganoderic acid A (GAA) as a potent anti-senescent compound with low toxicity and favorable drug properties through high-content screening. GAA, a major natural component of Ganoderma lucidum, possesses broad-spectrum geroprotective activity across various species. In C. elegans, GAA treatment extends lifespan and healthspan as effectively as rapamycin....
Li Chen

A fungal pathogen suppresses host leaf senescence to increase infection

1 week 2 days ago
Phytopathogens such as Puccinia striiformis f. sp. tritici (Pst) induce pigment retention at pathogen infection sites. Although pigment retention is commonly observed in diverse pathosystems, its underlying physiological mechanism remains largely unclear. Herein, we identify and characterize a wheat leaf senescence gene, TaSGR1, which enhances resistance against Pst by promoting leaf senescence and H(2)O(2) accumulation while inhibiting photosynthesis. Knockout of TaSGR1 (STAYGREEN) in wheat...
Yue Li

Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability

1 week 2 days ago
Maintenance of genome integrity is paramount to molecular programs in multicellular organisms. Throughout the lifespan, various endogenous and environmental factors pose persistent threats to the genome, which can result in DNA damage. Understanding the functional consequences of DNA damage requires investigating their preferred genomic distributions and influences on gene regulatory programs. However, such analysis is hindered by both the complex cell-type compositions within organs and the...
Dongsheng Bai

Optimal dietary patterns for healthy aging

1 week 2 days ago
As the global population ages, it is critical to identify diets that, beyond preventing noncommunicable diseases, optimally promote healthy aging. Here, using longitudinal questionnaire data from the Nurses' Health Study (1986-2016) and the Health Professionals Follow-Up Study (1986-2016), we examined the association of long-term adherence to eight dietary patterns and ultraprocessed food consumption with healthy aging, as assessed according to measures of cognitive, physical and mental health,...
Anne-Julie Tessier

Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape

1 week 2 days ago
Aging is reflected by genome-wide DNA methylation changes, which form the basis of epigenetic clocks, but it is largely unclear how these epigenetic modifications are regulated and whether they directly affect the aging process. In this study, we performed epigenetic editing at age-associated CpG sites to explore the consequences of interfering with epigenetic clocks. CRISPR-guided editing targeted at individual age-related CpGs evoked genome-wide bystander effects, which were highly...
Sven Liesenfelder

Drug-Based Lifespan Extension in Mice Strongly Affects Lipids Across Six Organs

1 week 2 days ago
Caloric restriction is associated with slow aging in model organisms. Additionally, some drugs have also been shown to slow aging in rodents. To better understand metabolic mechanisms that are involved in increased lifespan, we analyzed metabolomic differences in six organs of 12-month-old mice using five interventions leading to extended longevity, specifically caloric restriction, 17-α estradiol, and caloric restriction mimetics rapamycin, canagliflozin, and acarbose. These interventions...
Sara Greenfield