Aging & Longevity

Histone deficiency and hypoacetylation in the aging retinal pigment epithelium

1 month ago
Histones serve as a major carrier of epigenetic information in the form of post-translational modifications which are vital for controlling gene expression, maintaining cell identity, and ensuring proper cellular function. Loss of histones in the aging genome can drastically impact the epigenetic landscape of the cell leading to altered chromatin structure and changes in gene expression profiles. In this study, we investigated the impact of age-related changes on histone levels and histone...
Sushil K Dubey

Interplay between autophagy and CncC regulates dendrite pruning in <em>Drosophila</em>

1 month ago
Autophagy is essential for the turnover of damaged organelles and long-lived proteins. It is responsible for many biological processes such as maintaining brain functions and aging. Impaired autophagy is often linked to neurodevelopmental and neurodegenerative diseases in humans. However, the role of autophagy in neuronal pruning during development remains poorly understood. Here, we report that autophagy regulates dendrite-specific pruning of ddaC sensory neurons in parallel to local caspase...
Jue Yu Kelly Tan

Enhancing chimeric antigen receptor T cell therapy by modulating the p53 signaling network with Δ133p53α

1 month ago
Chimeric antigen receptor (CAR) T cell dysfunction is a major barrier to achieving lasting remission in hematologic cancers, especially in chronic lymphocytic leukemia (CLL). We have shown previously that Δ133p53α, an endogenous isoform of the human TP53 gene, decreases in expression with age in human T cells, and that reconstitution of Δ133p53α in poorly functional T cells can rescue proliferation [A. M. Mondal et al., J. Clin. Invest. 123, 5247-5257 (2013)]. Although Δ133p53α lacks a...
Christopher Roselle

S100A8-enriched microglia populate the brain of tau-seeded and accelerated aging mice

1 month ago
Long considered to fluctuate between pro- and anti-inflammatory states, it has now become evident that microglia occupy a variegated phenotypic landscape with relevance to aging and neurodegeneration. However, whether specific microglial subsets converge in or contribute to both processes that eventually affect brain function is less clear. To investigate this, we analyzed microglial heterogeneity in a tauopathy mouse model (K18-seeded P301L) and an accelerated aging model...
Roxane Gruel

Mechanisms of sex differences in Alzheimer's disease

1 month ago
Alzheimer's disease (AD) and the mechanisms underlying its etiology and progression are complex and multifactorial. The higher AD risk in women may serve as a clue to better understand these complicated processes. In this review, we examine aspects of AD that demonstrate sex-dependent effects and delve into the potential biological mechanisms responsible, compiling findings from advanced technologies such as single-cell RNA sequencing, metabolomics, and multi-omics analyses. We review evidence...
Chloe Lopez-Lee

An iron rheostat controls hematopoietic stem cell fate

1 month 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 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 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 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 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 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 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 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 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 1 week 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 1 week 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 1 week 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
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