Aging & Longevity

Intracellular magnesium optimizes transmission efficiency and plasticity of hippocampal synapses by reconfiguring their connectivity

1 month ago
Synapses at dendritic branches exhibit specific properties for information processing. However, how the synapses are orchestrated to dynamically modify their properties, thus optimizing information processing, remains elusive. Here, we observed at hippocampal dendritic branches diverse configurations of synaptic connectivity, two extremes of which are characterized by low transmission efficiency, high plasticity and coding capacity, or inversely. The former favors information encoding, pertinent...
Hang Zhou

An approach to identify gene-environment interactions and reveal new biological insight in complex traits

1 month ago
There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a...
Xiaofeng Zhu

Matching actions to needs: shifting policy responses to the changing health needs of Chinese children and adolescents

1 month ago
China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts,...
Tian-Jiao Chen

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a…

1 month ago
BACKGROUND: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It...
GBD 2021 Diseases and Injuries Collaborators

Inflammation and mitophagy are mitochondrial checkpoints to aging

1 month ago
Cellular and organismal aging have been consistently associated with mitochondrial dysfunction and inflammation. Accumulating evidence indicates that aging-related inflammatory responses are mechanistically linked to compromised mitochondrial integrity coupled with mtDNA-driven CGAS activation, a process that is tonically inhibited by mitophagy.
Emma Guilbaud

Free ribosomal proteins as culprits for nucleolar stress

1 month ago
Nucleolar stress has been consistently linked to age-related diseases. In this issue, Sirozh et al.¹ find that the common molecular signature of nucleolar stress is the accumulation of free ribosomal proteins, which leads to premature aging in mice; however, it can be reversed by mTOR inhibition.
Ina Huppertz

The advent of Alzheimer treatments will change the trajectory of human aging

1 month ago
Slowing neurodegenerative disorders of late life has lagged behind progress on other chronic diseases. But advances in two areas, biochemical pathology and human genetics, have now identified early pathogenic events, enabling molecular hypotheses and disease-modifying treatments. A salient example is the discovery that antibodies to amyloid ß-protein, long debated as a causative factor in Alzheimer's disease (AD), clear amyloid plaques, decrease levels of abnormal tau proteins and slow cognitive...
Dennis J Selkoe

NMR metabolomic modeling of age and lifespan: A multicohort analysis

1 month ago
Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear...
Chung-Ho E Lau

Epigenetic age oscillates during the day

1 month ago
Since their introduction, epigenetic clocks have been extensively used in aging, human disease, and rejuvenation studies. In this article, we report an intriguing pattern: epigenetic age predictions display a 24-h periodicity. We tested a circadian blood sample collection using 17 epigenetic clocks addressing different aspects of aging. Thirteen clocks exhibited significant oscillations with the youngest and oldest age estimates around midnight and noon, respectively. In addition, daily...
Karolis Koncevičius

LKRSDH-dependent histone modifications of insulin-like peptide sites contribute to age-related circadian rhythm changes

1 month ago
To understand aging impact on the circadian rhythm, we screened for factors influencing circadian changes during aging. Our findings reveal that LKRSDH mutation significantly reduces rhythmicity in aged flies. RNA-seq identifies a significant increase in insulin-like peptides (dilps) in LKRSDH mutants due to the combined effects of H3R17me2 and H3K27me3 on transcription. Genetic evidence suggests that LKRSDH regulates age-related circadian rhythm changes through art4 and dilps. ChIP-seq analyzes...
Pengfei Lv

Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila

1 month ago
Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated...
Jenny Zhe Liao

Identification of senescent, TREM2-expressing microglia in aging and Alzheimer's disease model mouse brain

1 month ago
Alzheimer's disease (AD) and dementia in general are age-related diseases with multiple contributing factors, including brain inflammation. Microglia, and specifically those expressing the AD risk gene TREM2, are considered important players in AD, but their exact contribution to pathology remains unclear. In this study, using high-throughput mass cytometry in the 5×FAD mouse model of amyloidosis, we identified senescent microglia that express high levels of TREM2 but also exhibit a distinct...
Noa Rachmian

LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD(+) depletion

1 month ago
Although dysregulated cholesterol metabolism predisposes aging tissues to inflammation and a plethora of diseases, the underlying molecular mechanism remains poorly defined. Here, we show that metabolic and genotoxic stresses, convergently acting through liver X nuclear receptor, upregulate CD38 to promote lysosomal cholesterol efflux, leading to nicotinamide adenine dinucleotide (NAD^(+)) depletion in macrophages. Cholesterol-mediated NAD^(+) depletion induces macrophage senescence, promoting...
Ryo Terao

Towards prolonging ovarian reproductive life: Insights into trace elements homeostasis

1 month ago
Ovarian aging is marked by a reduction in the quantity and quality of ovarian follicles, leading to a decline in female fertility and ovarian endocrine function. While the biological characteristics of ovarian aging are well-established, the exact mechanisms underlying this process remain elusive. Recent studies underscore the vital role of trace elements (TEs) in maintaining ovarian function. Imbalances in TEs can lead to ovarian aging, characterized by reduced enzyme activity, hormonal...
Weicheng Tang

Aging as a loss of morphostatic information: A developmental bioelectricity perspective

1 month ago
Maintaining order at the tissue level is crucial throughout the lifespan, as failure can lead to cancer and an accumulation of molecular and cellular disorders. Perhaps, the most consistent and pervasive result of these failures is aging, which is characterized by the progressive loss of function and decline in the ability to maintain anatomical homeostasis and reproduce. This leads to organ malfunction, diseases, and ultimately death. The traditional understanding of aging is that it is caused...
Léo Pio-Lopez

Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence

1 month ago
Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in aging and are targets of DNA damage response. Although we and others have demonstrated presence of short telomeres in genetic cardiomyopathic and heart failure cardiomyocytes, little is known about the role of telomere lengths in cardiomyocyte. Here, we demonstrate that in heart failure patient cardiomyocytes, telomeres are shortened compared to healthy controls. We generated isogenic...
Bin Li

Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence

1 month 1 week ago
Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting...
Xue Han

Aging-induced MCPH1 translocation activates necroptosis and impairs hematopoietic stem cell function

1 month 1 week ago
DNA damage contributes to the aging of hematopoietic stem cells (HSCs), yet the underlying molecular mechanisms are not fully understood. In this study, we identified a heterogeneous functional role of microcephalin (MCPH1) in the nucleus and cytoplasm of mouse HSCs. In the nucleus, MCPH1 maintains genomic stability, whereas in the cytoplasm, it prevents necroptosis by binding with p-RIPK3. Aging triggers MCPH1 translocation from cytosol to nucleus, reducing its cytoplasmic retention and leading...
Hanqing He

DNA double-strand break-capturing nuclear envelope tubules drive DNA repair

1 month 1 week ago
Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC)...
Mitra Shokrollahi

Perturbation-induced granular fluidization as a model for remote earthquake triggering

1 month 1 week ago
Studying the effect of mechanical perturbations on granular systems is crucial for understanding soil stability, avalanches, and earthquakes. We investigate a granular system as a laboratory proxy for fault gouge. When subjected to a slow shear, granular materials typically exhibit a stress overshoot before reaching a steady state. We find that short seismic pulses can reset a granular system flowing in steady state so that the stress overshoot is regenerated. This feature is shown to determine...
Kasra Farain
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