Aging & Longevity

Sleep is crucial for cognitive functions and life span across species. While sleep homeostasis and cognitive processes are linked through cellular and synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac (inc) short sleep mutants, which lack an adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited enhanced Pavlovian aversive olfactory learning and memory, unlike other sleep mutants with normal or reduced...

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Individual heterogeneity shapes ecoevolutionary processes at multiple scales. Yet, the scarcity of long-term life-history data and limitations in classic statistical tools hinder our capacity to uncover and understand individual heterogeneity in wildlife populations. Here, we apply an underused multivariate statistical method to uncover four heterogenous life-history trajectories in wild female bighorn sheep (Ovis canadensis). Remarkably, these trajectories had remained unobserved in the...

The surgical treatment of geriatric patients represents a major challenge in traumatology. It is well known that aging affects fracture healing. However, the exact pathophysiology of age-related changes in angiogenesis, inflammation and bone remodeling remains still elusive. Therefore, we herein studied the differences of femoral fracture healing in young adult (3-4 months) and aged (16-18 months) CD-1 mice by using a stable closed femoral fracture model with intramedullary screw fixation. The...

N-acetyltransferase 10 (NAT10) is involved in regulating senescence. However, its role in glomerular diseases remains unclear. Therefore, this study aims to investigate the mechanisms by which NAT10 influences senescence and damage in an adriamycin (ADR)-induced nephropathy model. Senescence (p16 and p21) and DNA damage markers (γ-H2AX (ser139)) were assessed in ADR-induced nephropathy. NAT10 function was demonstrated using Remodelin or small interfering RNA (siRNA) interventions. Transcriptome...

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Ferroptosis is closely linked with various pathophysiological processes, including aging, neurodegeneration, ischemia-reperfusion injury, viral infection and, notably, cancer progression; however, its post-translational regulatory mechanisms remain incompletely understood. Here we revealed a crucial role of S-palmitoylation in regulating ferroptosis through glutathione peroxidase 4 (GPX4), a pivotal enzyme that mitigates lipid peroxidation. We identified that zinc finger DHHC-domain containing...

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The landscapes of somatic mutation in normal cells inform us about the processes of mutation and selection operative throughout life, providing insight into normal ageing and the earliest stages of cancer development¹. Here, by whole-genome sequencing of 238 microdissections² from 30 individuals, including 18 with gastric cancer, we elucidate the developmental trajectories of normal and malignant gastric epithelium. We find that gastric glands are units of monoclonal cell populations that accrue...

CONCLUSION: The study highlights the strong association between elder abuse, pain with depression, especially among older female. These findings underscore the need for targeted public health interventions among vulnerable groups such as older female, and future research to explore cross- national dynamics and underlying risk factors.

The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains unknown whether these modes (i.e. gradients) persist across the adult human lifespan, and...

Untangling the functional organisation of a brain region crucial for memory and learning helps reveal how individual differences are linked to variations in recall ability, aging and dopamine receptor distribution.

Genome-wide association studies (GWAS) have identified loci associated with kidney diseases, but the causal variants, genes, and pathways involved remain elusive. Here, we identified a kidney disease gene called pancreatic progenitor cell differentiation and proliferation factor (PPDPF) through integrating GWAS on kidney function and multiomic analysis. PPDPF was predominantly expressed in healthy proximal tubules of human and mouse kidneys via single-cell analysis. Further investigations...

Our previous transcriptomic analysis revealed an up-regulation of the antiapoptotic protein B cell lymphoma-extra large (Bcl-xL) in centenarians relative to octogenarians or younger cohorts. In this study, we used Bcl-xL-overexpressing mice to assess its impact on successful aging. Our findings indicate that Bcl-xL overexpression modifies T cell subsets and improves their metabolism, apoptosis resistance, macroautophagy, and cytokine production during aging. This more resilient immune system...

Defective DNA damage response (DDR) and mitochondrial dysfunction are a major etiology of tissue impairment and aging. Mitochondrial autophagy (mitophagy) is a mitochondrial quality control (MQC) mechanism to selectively eliminate dysfunctional mitochondria. ATR (ataxia-telangiectasia and Rad3-related) is a key DDR regulator playing a pivotal role in DNA replication stress response and genomic stability. Paradoxically, the human Seckel syndrome caused by ATR mutations exhibits premature aging...

CONCLUSION: The ML results indicate that two tree-based methods (RF and GB) are reliable and effective as initial models for classification tasks involving discrete clinical aging and neurodegeneration data. In the XAI phase, SHAP performed better than LIME due to lower computational time (when applied to RF and GB) and incorporation of feature interactions, leading to more reliable results.

This review focuses on sexual dimorphism in cellular senescence and senolytic treatment in relation to brain health and age-related cognitive decline. The stressors of aging, DNA damage, inflammation, and oxidative stress induce cell senescence, a hallmark of aging. Senescent cells change their function and molecular profile and are primed to release pro-inflammatory cytokines. The functional changes include the activation of cell signals to prevent cell death. The release of pro-inflammatory...

INTRODUCTION: Neurophysiological activity, as noninvasively captured by electro- and magnetoencephalography (EEG and MEG), demonstrates complex temporal fluctuations approximated by typical variations around the mean values and rare events with large amplitude. The statistical properties of these extreme and rare events in neurodynamics may reflect the limits or capacity of the brain as a complex system in information processing. However, the exact role of these extreme neurodynamic events in...

Understanding the trajectory of in vivo locus coeruleus (LC) signal intensity across the adult lifespan and among various demographic groups, particularly during middle age, may be crucial for early detection of neurodegenerative diseases, which begin in the LC decades before symptom onset. Even though pathological changes in the LC are thought to begin in middle age, its characteristics across the adult lifespan, and its consistency and variation across demographic groups, remain not well...

Regulatory T cells (Tregs) are important in maintaining tolerance and are key players in immunity. In aging, increased Treg function along with low-grade inflammation has been reported. This dichotomy of enhanced Treg function along with inflammation highlights the importance of understanding Treg biology and communication patterns in the very old. In this proof-of-concept study, we demonstrate that aged Tregs (85 years) do not significantly communicate with CD4^(+) and CD8^(+) T effectors when...