Aging & Longevity
Computational memory capacity predicts aging and cognitive decline
Memory is a crucial cognitive function that deteriorates with age. However, this ability is normally assessed using cognitive tests instead of the architecture of brain networks. Here, we use reservoir computing, a recurrent neural network computing paradigm, to assess the linear memory capacities of neural-network reservoirs extracted from brain anatomical connectivity data in a lifespan cohort of 636 individuals. The computational memory capacity emerges as a robust marker of aging, being...
Mitochondrial quality control in cardiomyocytes: safeguarding the heart against disease and ageing
Mitochondria are multifunctional organelles that are important for many different cellular processes, including energy production and biosynthesis of fatty acids, haem and iron-sulfur clusters. Mitochondrial dysfunction leads to a disruption in these processes, the generation of excessive reactive oxygen species, and the activation of inflammatory and cell death pathways. The consequences of mitochondrial dysfunction are particularly harmful in energy-demanding organs such as the heart. Loss of...
Texasin, A main product from Caragana Jubata (Pall.) Poir, induces proliferation arrest and protective autophagy in lung adenocarcinoma
CONCLUSIONS: Texasin emerges as a promising non-cytotoxic anti-lung adenocarcinoma cancer compound, significantly inhibiting malignant phenotypes, highlighting its potential for lung adenocarcinoma cancer therapy.
Sociodemographic Factors in Older Adults' Gait Speed Decline: A Gender Disaggregate Growth Curve Analysis of the Ibadan Longitudinal Study of Ageing
BackgroundGait speed is an important predictor of older adults' well-being. We estimated the influence of sociodemographic factors on the gait speed decline of community-dwelling older Nigerians.MethodsUsing the Ibadan Study of Ageing (2007, 2008, and 2009 cycles), we completed a gender disaggregate analysis of sociodemographic influences on participants' gait speed trajectory using mixed-design ANOVA and growth curve analysis.ResultsAt baseline, 53.2% of participants were female, 61.9% were...
Chronic alcohol consumption accelerates cardiovascular aging and decreases cardiovascular reserve capacity
The pathology of cardiovascular aging is complex, involving mitochondrial dysfunction, oxidative and nitrative stress, oxidative DNA injury, impaired lipid metabolism, cell death, senescence, and chronic inflammation. These processes lead to remodeling and structural changes in the cardiovascular system, resulting in a progressive decline in cardiovascular reserve capacity and health, and an increased risk of diseases and mortality. Excessive alcohol consumption exacerbates these risks by...
Enhanced memory despite severe sleep loss in Drosophila insomniac mutants
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...
Erratum for the Report "A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging" by W. Zhang et al
No abstract
Uncovering bighorn sheep life-history trajectories in multidimensional trait space
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...
Age-related alterations of angiogenesis, inflammation and bone microarchitecture during fracture healing in mice
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...
NAT10 mediates TLR2 to promote podocyte senescence in adriamycin-induced nephropathy
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...
Interplay of somatic mutations and epigenetic aging clocks
No abstract
Palmitoylation of GPX4 via the targetable ZDHHC8 determines ferroptosis sensitivity and antitumor immunity
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...
Structural basis of augmenting taurine uptake by the taurine transporter in alleviating cellular senescence
No abstract
The somatic mutation landscape of normal gastric epithelium
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...
Gender differences in the association between elder abuse and pain with depression among older adults in India: insights from a cross-sectional survey
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.
Two long-axis dimensions of hippocampal-cortical integration support memory function across the adult lifespan
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...
Mapping out overlapping connectivity patterns
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.
PPDPF preserves integrity of proximal tubule by modulating NMNAT activity in chronic kidney diseases
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...
Bcl-xL overexpression in T cells preserves muscle mitochondrial structure and function and prevents frailty in old mice
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...
DNA damage response regulator ATR licenses PINK1-mediated mitophagy
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...
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