Aging & Longevity

An iron rheostat controls hematopoietic stem cell fate

1 month 2 weeks ago
Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response...
Yun-Ruei Kao

Multiomics insights into the female reproductive aging

1 month 2 weeks ago
The human female reproductive lifespan significantly diminishes with age, leading to decreased fertility, reduced fertility quality and endocrine function disorders. While many aspects of aging in general have been extensively documented, the precise mechanisms governing programmed aging in the female reproductive system remain elusive. Recent advancements in omics technologies and computational capabilities have facilitated the emergence of multiomics deep phenotyping. Through the application...
Simin Wei

Understanding age-related pathologic changes in TDP-43 functions and the consequence on RNA splicing and signalling in health and disease

1 month 2 weeks ago
TAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process. In neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various...
Flora Cheng

Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans

1 month 2 weeks ago
Ribosome biogenesis is initiated by RNA polymerase I (Pol I)-mediated synthesis of pre-ribosomal RNA (pre-rRNA). Pol I activity was previously linked to longevity, but the underlying mechanisms were not studied beyond effects on nucleolar structure and protein translation. Here we use multi-omics and functional tests to show that curtailment of Pol I activity remodels the lipidome and preserves mitochondrial function to promote longevity in Caenorhabditis elegans. Reduced pre-rRNA synthesis...
Samim Sharifi

Vitamin D and ischemic stroke - Association, mechanisms, and therapeutics

1 month 2 weeks ago
Confronting the rising tide of ischemic stroke and its associated mortality and morbidity with ageing, prevention and acute management of ischemic stroke is of paramount importance. Mounting observational studies have established a non-linear association of vitamin D status with cardiovascular diseases, including ischemic stroke. Paradoxically, current clinical trials fail to demonstrate the cardiovascular benefits of vitamin D supplementation. We aim to update recent clinical and experimental...
Pan Cui

Genome-wide profiles of DNA damage represent highly accurate predictors of mammalian age

1 month 2 weeks ago
The identification of novel age-related biomarkers represents an area of intense research interest. Despite multiple studies associating DNA damage with aging, there is a glaring paucity of DNA damage-based biomarkers of age, mainly due to the lack of precise methods for genome-wide surveys of different types of DNA damage. Recently, we developed two techniques for genome-wide mapping of the most prevalent types of DNA damage, single-strand breaks and abasic sites, with nucleotide-level...
Huifen Cao

Alternative Wnt-signaling axis leads to a break of oncogene-induced senescence

1 month 3 weeks ago
Oncogene-induced senescence (OIS) is an important process that suppresses tumor development, but the molecular mechanisms of OIS are still under investigation. It is known that BRAF^(V600E)-mutated melanocytes can overcome OIS and develop melanoma, but the underlying mechanism is largely unknown. Using an established OIS model of primary melanocytes transduced with BRAF^(V600E), YAP activity was shown to be induced in OIS as well as in melanoma cells compared to that in normal epidermal...
Viola Kluge

Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts

1 month 3 weeks ago
Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. In this study, using budding yeast and normal human fibroblasts, we found that cellular senescence-stable cell cycle arrest contributing to organismal aging-is the long-term outcome of PMD. Our genetic screening using budding yeast unexpectedly identified a close genetic association between...
Kojiro Suda

Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease

1 month 3 weeks ago
The brain is spatially organized and contains unique cell types, each performing diverse functions and exhibiting differential susceptibility to neurodegeneration. This is exemplified in Parkinson's disease with the preferential loss of dopaminergic neurons of the substantia nigra pars compacta. Using a Parkinson's transgenic model, we conducted a single-cell spatial transcriptomic and dopaminergic neuron translatomic analysis of young and old mouse brains. Through the high resolving capacity of...
Peter Kilfeather

Excitotoxicity and ALS: New therapy targets an old mechanism

1 month 3 weeks ago
Excitotoxicity-induced cell death in motor neurons is a major therapeutic target for amyotrophic lateral sclerosis (ALS). Yan et al.¹ present a novel compound to specifically disrupt extra-synaptic NMDAR complexes, extending the lifespan of the SOD1^(G93A) ALS mouse and ameliorating cell death.
Hannah Louise Smith

Selective degradation of ribosomes during oncogene-induced senescence: molecular insights and biological perspectives

1 month 3 weeks ago
Ribosomes are conserved macromolecular machines that are responsible for protein synthesis in all cells. While our knowledge of ribosome biogenesis and function has increased significantly in recent years, little is known about how ribosomes are degraded under specific cellular conditions. We recently uncovered that ribosomes are efficiently turned over by selective macroautophagy/autophagy during oncogene-induced senescence (OIS). By profiling the ribosome interactome in human fibroblasts...
Aida Rodríguez López

Transcription of endogenous retroviruses in senescent cells contributes to the accumulation of double-stranded RNAs that trigger an anti-viral response that reinforces senescence

1 month 3 weeks ago
An important epigenetic switch marks the onset and maintenance of senescence. This allows transcription of the genetic programs that arrest the cell cycle and alter the microenvironment. Transcription of endogenous retroviruses (ERVs) is also a consequence of this epigenetic switch. In this manuscript, we have identified a group of ERVs that are epigenetically silenced in proliferating cells but are upregulated during replicative senescence or during various forms of oncogene-induced senescence,...
Eros Di Giorgio

Multi-molecular hyperspectral PRM-SRS microscopy

1 month 3 weeks ago
Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt the native environment of cells/tissues, have limited spatial or spectral resolution, or cannot distinguish different lipid...
Wenxu Zhang

Biomarker Changes during 20 Years Preceding Alzheimer's Disease

1 month 3 weeks ago
CONCLUSIONS: In this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer's disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal. (Funded by the Key Project of the National Natural Science Foundation of China and others;...
Jianping Jia

Fast and slow: Recording neuromodulator dynamics across both transient and chronic time scales

1 month 3 weeks ago
Neuromodulators transform animal behaviors. Recent research has demonstrated the importance of both sustained and transient change in neuromodulators, likely due to tonic and phasic neuromodulator release. However, no method could simultaneously record both types of dynamics. Fluorescence lifetime of optical reporters could offer a solution because it allows high temporal resolution and is impervious to sensor expression differences across chronic periods. Nevertheless, no fluorescence lifetime...
Pingchuan Ma

Impact of ageing on homologous and human-coronavirus-reactive antibodies after SARS-CoV-2 vaccination or infection

1 month 3 weeks ago
The endemic human coronaviruses (HCoVs) circulate worldwide yet remain understudied and unmitigated. The observation of elevated levels of HCoV reactive antibodies in COVID-19 patients highlights the urgent necessity of better understanding of HCoV specific immunity. Here, we characterized in-depth the de novo SARS-CoV-2 specific antibody responses and the boosting of HCoV-reactive antibodies after SARS-CoV-2 vaccination or infection in individuals up to 98 years old. All the vaccinees were...
Fan Zhou
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