Aging & Longevity

CONCLUSION: The adoption of mobile health apps must be prioritized to assist individuals with dementia and their caregivers in low income countries. Future apps should focus on improving engagement and involving medical experts in development to increase credibility and utilization across socioeconomic levels and healthcare systems.

Aging is associated with increased variability and dysregulation of the immune system. We performed a system-level analysis of serum cytokines in a longitudinal cohort of 133 healthy individuals over 9 y. We found that cancer incidence is a major contributor to increased cytokine abundance variability. Circulating cytokines increase up to 4 y before a cancer diagnosis in subjects with age over 80 y. We also analyzed cytokine expression in 10 types of early-stage cancers from The Cancer Genome...

Decreased nicotinamide adenine dinucleotide (oxidized form) (NAD^(+)) levels are reportedly associated with several aging-related disorders. Thus, supplementation with NAD^(+) precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), exhibits beneficial effects against these disorders. However, the in vivo metabolic pathways of NMN and NR remain to be elucidated. In this study, we comprehensively analyzed the fate of orally and intravenously administered NMN and NR in...

Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD), an alloimmune fibrotic process leading to death or retransplantation after a median of 6 years. Immunosuppression fails to prevent CLAD, suggesting the existence of drug-resistant alloimmune pathways. We used time-of-flight mass cytometry to identify cells enriched in the bronchoalveolar lavage of patients with subsequent acute lung allograft dysfunction (ALAD), a risk factor for CLAD. We show that...

Vascular cognitive impairment (VCI) is a leading cause of age-related cognitive decline, driven by cerebrovascular dysfunction and cerebral small vessel disease (CSVD). Emerging evidence suggests that cerebromicrovascular endothelial senescence plays an important role in the pathogenesis of VCI by promoting cerebral blood flow dysregulation, neurovascular uncoupling, blood-brain barrier (BBB) disruption, and the development of cerebral microhemorrhages (CMHs). This review explores the concept of...

Emerging evidence has unveiled heterogeneity in phenotypic and transcriptional alterations at the single-cell level during oxidative stress and senescence. Despite the pivotal roles of cellular metabolism, a comprehensive elucidation of metabolomic heterogeneity in cells and its connection with cellular oxidative and senescent status remains elusive. By integrating single-cell live imaging with mass spectrometry (SCLIMS), we establish a cross-modality technique capturing both metabolome and...

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...

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...

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.

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...

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...

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...