Aging & Longevity

PPGR: a comprehensive perennial plant genomes and regulation database

3 weeks 4 days ago
Perennial woody plants hold vital ecological significance, distinguished by their unique traits. While significant progress has been made in their genomic and functional studies, a major challenge persists: the absence of a comprehensive reference platform for collection, integration and in-depth analysis of the vast amount of data. Here, we present PPGR (Resource for Perennial Plant Genomes and Regulation; to address this critical gap, by collecting, integrating,...
Sen Yang

Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel

3 weeks 5 days ago
In Alzheimer disease (AD), amyloid precursor protein (APP) and production of amyloid beta (Aβ) which is generated by amyloidogenic pathway is implicated in neurotoxicity and neuronal cell deaths. However, physiological Aβ level is essential to improves neuronal survival, attenuates neuronal apoptosis and has neuroprotective effect. In addition, physiological APP level has neurotrophic effect on the central nervous system (CNS). APP has a critical role in the brain growth and development via...
Hayder M Al-Kuraishy

LensAge index as a deep learning-based biological age for self-monitoring the risks of age-related diseases and mortality

3 weeks 5 days ago
Age is closely related to human health and disease risks. However, chronologically defined age often disagrees with biological age, primarily due to genetic and environmental variables. Identifying effective indicators for biological age in clinical practice and self-monitoring is important but currently lacking. The human lens accumulates age-related changes that are amenable to rapid and objective assessment. Here, using lens photographs from 20 to 96-year-olds, we develop LensAge to reflect...
Ruiyang Li

SCAN: Spatiotemporal Cloud Atlas for Neural cells

3 weeks 5 days ago
The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge...
Yushan Deng

Genetic variations in G-quadruplex forming sequences affect the transcription of human disease-related genes

3 weeks 5 days ago
Guanine-rich DNA strands can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4s). G4s folded in proximal promoter regions (PPR) are associated either with positive or negative transcriptional regulation. Given that single nucleotide variants (SNVs) affecting G4 folding (G4-Vars) may alter gene transcription, and that SNVs are associated with the human diseases' onset, we undertook a novel comprehensive study of the G4-Vars genome-wide (G4-variome) to find...
Agustín Lorenzatti

Autophagy-mediated control of ribosome homeostasis in oncogene-induced senescence

3 weeks 5 days ago
Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent alterations in the ribosomal interactome, we find that the deubiquitinase USP10 dissociates from the...
Aida Rodríguez López

Reimagining infrastructure for a biodiverse future

3 weeks 5 days ago
Civil infrastructure will be essential to face the interlinked existential threats of climate change and rising resource demands while ensuring a livable Anthropocene for all. However, conventional infrastructure planning largely neglects the contributions and maintenance of Earth's ecological life support systems, which provide irreplaceable services supporting human well-being. The stability and performance of these services depend on biodiversity, but conventional infrastructure practices,...
Charles B van Rees

ChatGPT's Dance with Neuropsychological Data: a case study in Alzheimer's Disease

3 weeks 6 days ago
Artificial intelligence continues to revolutionize the medical and scientific field, especially with the release of ChatGPT. We assessed whether it provides an accurate interpretation of neuropsychological screening. We provided ChatGPT with the neuropsychological data of a patient with mild Alzheimer's Disease and invited it and two neuropsychologists to interpret the data. While ChatGPT provided an accurate interpretation of scores on each of the neuropsychological tests, it did not use...
Mohamad El Haj

Integrative multi-omic profiling of adult mouse brain endothelial cells and potential implications in Alzheimer's disease

3 weeks 6 days ago
The blood-brain barrier (BBB) is primarily manifested by a variety of physiological properties of brain endothelial cells (ECs), but the molecular foundation for these properties remains incompletely clear. Here, we generate a comprehensive molecular atlas of adult brain ECs using acutely purified mouse ECs and integrated multi-omics. Using RNA sequencing (RNA-seq) and proteomics, we identify the transcripts and proteins selectively enriched in brain ECs and demonstrate that they are partially...
Min Yu

c-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8<sup>+</sup> T cell immunity

3 weeks 6 days ago
During infection, virus-specific CD8^(+) T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8^(+) T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b). Following activation, c-Myc increases the levels of Cul4b and other members of the...
Asif A Dar

Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging

4 weeks ago
Aβ peptides derived from the amyloid precursor protein (APP) have been strongly implicated in the pathogenesis of Alzheimer's disease. However, the normal function of APP and the importance of that role in neurodegenerative disease is less clear. We recover the Drosophila ortholog of APP, Appl, in an unbiased forward genetic screen for neurodegeneration mutants. We perform comprehensive single cell transcriptional and proteomic studies of Appl mutant flies to investigate Appl function in the...
Vanitha Nithianandam

Dissecting the human leptomeninges at single-cell resolution

4 weeks ago
Emerging evidence shows that the meninges conduct essential immune surveillance and immune defense at the brain border, and the dysfunction of meningeal immunity contributes to aging and neurodegeneration. However, no study exists on the molecular properties of cell types within human leptomeninges. Here, we provide single nuclei profiling of dissected postmortem leptomeninges from aged individuals. We detect diverse cell types, including unique meningeal endothelial, mural, and fibroblast...
Nicola A Kearns

Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment

4 weeks ago
Engulfment of cellular material and proteins is a key function for microglia, a resident macrophage of the central nervous system (CNS). Among the techniques used to measure microglial engulfment, confocal light microscopy has been used the most extensively. Here, we show that autofluorescence (AF) likely due to lipofuscin (lipo-AF) and typically associated with aging, can also be detected within microglial lysosomes in the young mouse brain by light microscopy. This lipo-AF signal accumulates...
Jacob M Stillman

GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability

4 weeks ago
Age-associated hypercoagulability is accompanied by the increase of plasma levels of some coagulation factors including fibrinogen which may contribute to the increased risk of cardiovascular, cerebrovascular, and thrombotic diseases in elderly people. However, the underlying mechanism of increased plasma fibrinogen concentration during aging is still elusive. GRSF1 belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily. Here, we report that GRSF1 attenuates...
Doudou Liu

The ageing thyroid: implications for longevity and patient care

4 weeks ago
Thyroid hormones have vital roles in development, growth and energy metabolism. Within the past two decades, disturbances in thyroid hormone action have been implicated in ageing and the development of age-related diseases. This Review will consider results from biomedical studies that have identified the importance of precise temporospatial regulation of thyroid hormone action for local tissue maintenance and repair. Age-related disturbances in the maintenance of tissue homeostasis are thought...
Diana van Heemst

Epithelial-mesenchymal transition in age-associated thymic involution: Mechanisms and therapeutic implications

4 weeks 1 day ago
The thymus is a critical immune organ with endocrine and immune functions that plays important roles in the physiological and pathological processes of the body. However, with aging, the thymus undergoes degenerative changes leading to decreased production and output of naive T cells and the secretion of thymic hormones and related cytokines, thereby promoting the occurrence and development of various age-associated diseases. Therefore, identifying essential processes that regulate...
Jiali Yang

Transcriptional elongation control in developmental gene expression, aging, and disease

4 weeks 1 day ago
The elongation stage of transcription by RNA polymerase II (RNA Pol II) is central to the regulation of gene expression in response to developmental and environmental cues in metazoan. Dysregulated transcriptional elongation has been associated with developmental defects as well as disease and aging processes. Decades of genetic and biochemical studies have painstakingly identified and characterized an ensemble of factors that regulate RNA Pol II elongation. This review summarizes recent...
Yuki Aoi

Regulatory T cells shield muscle mitochondria from interferon-γ-mediated damage to promote the beneficial effects of exercise

4 weeks 1 day ago
Exercise enhances physical performance and reduces the risk of many disorders such as cardiovascular disease, type 2 diabetes, dementia, and cancer. Exercise characteristically incites an inflammatory response, notably in skeletal muscles. Although some effector mechanisms have been identified, regulatory elements activated in response to exercise remain obscure. Here, we have addressed the roles of Foxp3^(+)CD4^(+) regulatory T cells (T(regs)) in the healthful activities of exercise via...
P Kent Langston

Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal

4 weeks 1 day ago
A long-standing goal of amyloid research has been to characterize the structural basis of the rate-determining nucleating event. However, the ephemeral nature of nucleation has made this goal unachievable with existing biochemistry, structural biology, and computational approaches. Here, we addressed that limitation for polyglutamine (polyQ), a polypeptide sequence that causes Huntington's and other amyloid-associated neurodegenerative diseases when its length exceeds a characteristic threshold....
Tej Kandola

A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer's disease

4 weeks 1 day ago
Many aging individuals accumulate the pathology of Alzheimer's disease (AD) without evidence of cognitive decline. Here we describe an integrated neurodegeneration checkpoint response to early pathological changes that restricts further disease progression and preserves cognitive function. Checkpoint activation is mediated by the REST transcriptional repressor, which is induced in cognitively-intact aging humans and AD mouse models at the onset of amyloid β-protein (Aβ) deposition and tau...
Liviu Aron
8 minutes 37 seconds ago
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