Recent discoveries in hepatocellular carcinoma (HCC) unveil key molecules. However, due to liver cancer's high heterogeneity, predicting patient prognosis is challenging. This study aims to construct a model for predicting HCC prognosis using multiple key genes.

Aging of the epidermis partially occurs as a consequence of epidermal cell senescence, a non-proliferative state in which cells remain metabolically active and acquire changes in their secretome. We previously reported that senescent normal human epidermal keratinocytes (NHEKs) have two opposite outcomes: either cell death by excess of autophagic activity or escape from senescence to give rise to post-senescence neoplastic emerging (PSNE) cells. In this study, we investigated the role of PTGS2, the inducible enzyme of the prostaglandin biosynthesis pathway, in the onset of NHEK senescence and in the switch from senescence to pre-transformation. We provide evidence that the PTGS2/PGE/EP4 pathway plays a critical role in NHEK senescence as well as in senescence escape. We show that treating proliferating NHEKs with prostaglandin E (PGE) or with an agonist of one of its receptors, EP4, induced the establishment of the senescent phenotype, according to several markers including the senescence-associated β-galactosidase activity. Conversely, treating already senescent NHEKs with an antagonist of EP4, or knocking-down PTGS2 by siRNA resulted in the decrease of the percentage of senescence-associated β-galactosidase-positive cells. We also demonstrate that the PSNE frequency was significantly decreased upon PTGS2 silencing by siRNA, pharmacological PTGS2 inhibition, or treatment by an EP4 antagonist, while on the contrary treatments with PGE or EP4 agonist increased the PSNE frequency. These results indicate that the PTGS2/PGE/EP4 pathway is required to induce and maintain the senescent phenotype of NHEKs, and that PGE level is a potential determinant of the initial steps of the age-related oncogenic process.

People living with sickle cell disease (SCD) experience complications indicative of an accelerated aging phenotype typified by early decline in physical function and increased risk for age-related conditions. Cellular senescence, measured by expression of p16 in peripheral T-lymphocytes, is recognized as one of the underlying contributors to organismal aging. To examine if cellular senescence is increased in SCD patients, we cross-sectionally measured and compared expression of p16 mRNA in peripheral blood T lymphocytes in 18 adolescents and young adults with SCD to 27 similarly aged individuals without SCD. Expression of p16 was dramatically higher in individuals with SCD vs. without SCD (10.1 vs. 8.7 log p16 units, respectively, < 0.001) - a gap of 43 years in biological age - consistent with accelerated aging in the SCD population. Race was not associated with the increased p16 expression in the SCD group. These initial results suggest that individuals with SCD have a significantly higher cellular senescence burden which may contribute to premature aging, physiological decline, and excess morbidities. Additional longitudinal assessment and consideration for trials of senolytic therapies among individuals living with SCD and high p16 expression are warranted to improve their health span.

This study aimed to investigate the role of LncRNA differentiation antagonizing non-protein coding RNA (DANCR) in acute myocardial infarction (AMI).

Predicting prognosis in lung cancer patients is important in establishing future treatment and monitoring plans. Lung adenocarcinoma (LUAD) is the most common and aggressive type of lung cancer with dismal prognosis and prognostic stratification would help to guide treatment. Aberrant DNA methylation in tumors occurs earlier than clinical variations, and keeps accumulating as cancer progresses. Preliminary studies have given us some clues that DNA methylation might serve as a promising biomarker for prognosis prediction. Herein, we aimed to study the potential utility of DNA methylation pattern in predicting the recurrence risk of early stage resectable LUAD and to develop a risk-modeling signature based on differentially methylated regions (DMRs). This study consisted of three cohorts of 244 patients with stage I-IIIA LUAD, including marker discovery cohort ( = 39), prognostic model training cohort ( = 117) and validation cohort ( = 80). 468 DMRs between LUAD tumor and adjacent tissues were screened out in the marker discovery cohort (adjusted < 0.05), and a prognostic signature was developed based on 15 DMRs significantly related to disease-free survival in early stage LUAD patients. The DMR signature showed commendable performance in predicting the recurrence risk of LUAD patients both in model training cohort ( < 0.001; HR = 4.32, 95% CI = 2.39-7.80) and model validation cohort ( = 0.009; HR = 9.08, 95% CI = 1.20-68.80), which might be of great utility both for understanding the molecular basis of LUAD relapse, providing risk stratification of patients, and establishing future monitoring plans.

Sleep disturbances are a significant concern in individuals with dementia, affecting their overall health and quality of life, as well as that of their family members and caregivers. Dementia, a progressive neurodegenerative condition marked by cognitive decline, often coexists with various comorbidities such as cardiovascular disease, diabetes, obesity, anxiety/depression and thyroid disorders. These comorbidities can further impair cognitive function and complicate the clinical management of dementia, making it essential to address them in a holistic manner. This review critically examines the complex interplay between dementia and its associated comorbidities, with a special focus on the prevalence and impact of sleep disturbances. Sleep problems in dementia patients are not only common but also contribute to a faster progression of cognitive decline and increased burden on caregivers. The article explores the mechanisms by which these comorbidities, including cardiovascular conditions and metabolic disorders, exacerbate sleep disturbances and cognitive impairment in dementia patients. By synthesizing recent research findings, the review highlights the importance of identifying and managing modifiable risk factors for sleep disturbances in dementia. Integrated treatment approaches that address both cognitive and sleep-related challenges are essential for improving patient outcomes. The review also underscores the need for further research to develop targeted interventions that can effectively manage sleep disturbances in dementia, thereby enhancing the quality of life for both patients and caregivers. Understanding the relationship between dementia, comorbidities, and sleep disturbances is crucial for the development of comprehensive care strategies. This review aims to inform healthcare professionals about the current state of knowledge and encourage the implementation of evidence-based practices in dementia care.

Precursor T-cell acute lymphoblastic leukemia (Pre-T ALL) is a malignant neoplastic disease in which T-cells proliferate in the bone marrow. Single-cell sequencing technology could identify characteristic cell types, facilitating the study of the therapeutic mechanisms in Pre-T ALL.

Iron oxide nanomaterials (FeO NMs) have important biomedical and environmental applications, e.g. drug delivery, chemotherapy, magnetic resonance imaging contrast agents, etc. However, the environmental risks of such FeO are not fully assessed, particularly for soil living invertebrates, which are among the ones in the first line of exposure. Research has showed that longer-term exposure time is required to assess hazards of NMs, not predicted when based on shorter time and are therefore recommended. Thus, in the present study the effects of FeO NMs and FeCl were assessed in the terrestrial environment, using the soil model species (Oligochaeta), throughout its entire lifespan (202 days). Two animals' density were used: 1 (D1) and 40 (D40) animals per replicate, in LUFA 2.2 soil. The endpoints were survival and reproduction monitored over-time, up to 202 days. Results showed that density clearly affected the toxicity response, with higher toxicity and lower lifespan in D1 compared to D40. Overall, FeCl was more toxic than FeO NM in terms of reproduction, however, adult animals can be at higher (long-term) risk when exposed to FeO NM. Differences might be linked to slower Fe kinetics for the FeO NMs, i.e., slower Fe dissolution and release of ions.

Frailty constitutes a major factor that puts the elderly at risk of health and functional deterioration.

Disruption of Eph-ephrin bidirectional signaling leads to human congenital and age-related cataracts, but the mechanisms for these opacities in the eye lens remain unclear. Eph receptors bind to ephrin ligands on neighboring cells to induce canonical ligand-mediated signaling. The EphA2 receptor also signals non-canonically without ligand binding in cancerous cells, leading to epithelial-to-mesenchymal transition (EMT). We have previously shown that the receptor EphA2 and the ligand ephrin-A5 have diverse functions in maintaining lens transparency in mice. Loss of ephrin-A5 leads to anterior cataracts due to EMT. Surprisingly, both canonical and non-canonical EphA2 activation are present in normal wild-type lenses and in the ephrin-A5 knockout lenses. Canonical EphA2 signaling is localized exclusively to lens epithelial cells and does not change with age. Non-canonical EphA2 signaling is in both epithelial and fiber cells and increases significantly with age. We hypothesize that canonical ligand-dependent EphA2 signaling is required for the morphogenesis and organization of hexagonal equatorial epithelial cells while non-canonical ligand-independent EphA2 signaling is needed for complex membrane interdigitations that change during fiber cell differentiation and maturation. This is the first demonstration of non-canonical EphA2 activation in a non-cancerous tissue or cell and suggests a possible physiological function for ligand-independent EphA2 signaling.

Lactate is gradually proved as the essential regulator in intercellular signal transduction, energy metabolism reprogramming, and histone modification. This study aims to clarify the diagnosis value of lactate metabolism-related genes in osteoarthritis (OA).

As a progressive neurodegenerative disease, the comprehensive understanding of the pathogenesis of Alzheimer's disease (AD) is yet to be clarified. Modifications in RNA, including m6A/m5C/m1A, affect the onset and progression of many diseases. Consequently, this study focuses on the role of methylation modification in the pathogenesis of AD.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, whose characteristic pathology involves progressive deficiency of dopaminergic neurons and generation of Lewy bodies (LBs). Aggregated and misfolded α-synuclein (α-syn) is the major constituent of LBs. As the newly discovered pathway of renin-angiotensin system (RAS), Angiotensin-(1-7) (Ang-(1-7)) and receptor Mas have attracted increasing attentions for their correlation with PD, but underlying mechanisms remain not fully clear. Based on above, this study established PD models of mice and primary dopaminergic neurons with AAV-hα-syn(A53T), then discussed the effects of Ang-(1-7)/Mas on α-syn level and neuronal apoptosis for these models combined with downstream long non-coding RNA (lncRNA) and microRNA (miRNA). Results showed that Ang-(1-7) alleviated behavioral impairments, rescued dopaminergic neurons loss and lowered α-syn expression in substantia nigra of hα-syn(A53T) overexpressed PD mice. We also discovered that Ang-(1-7) decreased level of α-syn and apoptosis in the hα-syn(A53T) overexpressed dopaminergic neurons through lncRNA NEAT1/miR-153-3p axis. Moreover, miR-153-3p level in peripheral blood is found negatively correlated with that of α-syn. In conclusion, our work not only showed neuroprotective effect and underlying mechanisms for Ang-(1-7) on α-syn and , but also brought new hope on miR-153-3p and NEAT1 for diagnosis and treatment in PD.

Werner syndrome of premature aging is caused by mutations in the WRN RECQ helicase/exonuclease, which functions in DNA replication, repair, transcription, and telomere maintenance. How the loss of WRN accelerates aging is not understood in full. Here we show that WRN is necessary for optimal constitutive heterochromatin levels in proliferating human fibroblasts. Locally, WRN deficiency derepresses SATII pericentromeric satellite repeats but does not reduce replication fork progression on SATII repeats. Globally, WRN loss reduces a subset of protein-protein interactions responsible for the organization of constitutive heterochromatin in the nucleus, namely, the interactions involving Lamin B1 and Lamin B receptor, LBR. Both the mRNA level and subcellular distribution of LBR are affected by WRN deficiency, and unlike the former, the latter phenotype does not require WRN catalytic activities. The phenotypes of heterochromatin disruption seen in WRN-deficient proliferating fibroblasts are also observed in WRN-proficient fibroblasts undergoing replicative or oncogene-induced senescence. WRN interacts with histone deacetylase 2, HDAC2; WRN/HDAC2 association is mediated by heterochromatin protein alpha, HP1α, and WRN complexes with HP1α and HDAC2 are downregulated in senescing cells. The data suggest that the effect of WRN loss on heterochromatin is separable from senescence program, but mimics at least some of the heterochromatin changes associated with it.

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

Age-related hearing loss (AHL) is a prevalent and multifaceted condition that significantly impacts a substantial portion of the aging population. Oxysterol Binding Protein-like 2 (OSBPL2) has been identified as a causal gene for hearing loss. However, its role in AHL is still unclear. In this study, we investigated the effect of OSBPL2 on the survival of cochlea hair cells. To simulate AHL , hair cell-like inner ear cells (HEI-OC1) were exposed to HO treatment. OSBPL2 expression was significantly increased in HEI-OC1 cells after HO treatment. OSBPL2 knockdown augmented cell death and apoptosis in HO-induced HEI-OC1 cells. Besides, HO treatment also led to the inactivation of the AKT and FOXG1 signaling pathways in HEI-OC1 cells. Mechanistically, OSBPL2 silencing reinforced the inactivation of the FOXG1 signaling pathway in HO-treated HEI-OC1 cells by inhibiting the AKT signaling pathway. Under HO treatment, AKT inhibition by MK2206 augmented the apoptosis of HEI-OC1 cells; on the contrary, AKT activation by SC79 treatment partially rescued the apoptosis of OSBPL2-knockdown HEI-OC1 cells. In addition, FOXG1 silencing significantly reversed the effects of AKT activation on OSBPL2-knockdown HEI-OC1 cells. Moreover, OSBPL2 expression and the activation status of the AKT/FOXG1 signaling pathway were confirmed in the cochleae of young and old C57BL/6 mice. In conclusion, our study provides evidence that OSBPL2 inhibition sensitizes HEI-OC1 cells to HO-induced apoptosis via inactivation of the AKT/FOXG1 signaling pathway, suggesting that OSBPL2 acts as an important regulator in AHL.

Brain aging is compared between (macaques and baboons), non-human (chimpanzees, orangutans, and gorillas), and their close relative, humans. β-amyloid deposition in the form of senile plaques (SPs) and cerebral β-amyloid angiopathy (CAA) is a frequent neuropathological change in non-human primate brain aging. SPs are usually diffuse, whereas SPs with dystrophic neurites are rare. Tau pathology, if present, appears later, and it is generally mild or moderate, with rare exceptions in rhesus macaques and chimpanzees. Behavior and cognitive impairment are usually mild or moderate in aged non-human primates. In contrast, human brain aging is characterized by early tau pathology manifested as neurofibrillary tangles (NFTs), composed of paired helical filaments (PHFs), progressing from the entorhinal cortex, hippocampus, temporal cortex, and limbic system to other brain regions. β-amyloid pathology appears decades later, involves the neocortex, and progresses to the paleocortex, diencephalon, brain stem, and cerebellum. SPs with dystrophic neurites containing PHFs and CAA are common. Cognitive impairment and dementia of Alzheimer's type occur in about 1-5% of humans aged 65 and about 25% aged 85. In addition, other proteinopathies, such as limbic-predominant TDP-43 encephalopathy, amygdala-predominant Lewy body disease, and argyrophilic grain disease, primarily affecting the archicortex, paleocortex, and amygdala, are common in aged humans but non-existent in non-human primates. These observations show that human brain aging differs from brain aging in non-human primates, and humans constitute the exception among primates in terms of severity and extent of brain aging damage.