Age-Related sncRNAs in Human Hippocampal Tissue Samples: Focusing on Deregulated miRNAs.

Small non-coding RNAs (sncRNAs), particularly microRNAs (miRNAs), play an important role in transcriptome regulation by binding to mRNAs and post-transcriptionally inhibiting protein production. This regulation occurs in both physiological and pathological conditions, where the expression of many miRNAs is altered. Previous reports by our group and others have demonstrated that miRNA expression is also altered during aging.

A Novel Class of FKBP12 Ligands Rescues Premature Aging Phenotypes Associated with Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder clinically characterized by progressive muscular weakness and multisystem degeneration, which correlates with the size of CTG expansion and MBLN decrease. These changes induce a calcium and redox homeostasis imbalance in several models that recapitulate the features of premature tissue aging. In this study, we characterized the impact of a new family of FKBP12 ligands (generically named MPs or MP compounds) designed to stabilize FKBP12 binding to the ryanodine receptors and normalize calcium dysregulation under oxidative stress.

Electronic health records reveal that COVID-19 impacted health resources and survival of Basque population.

Background: The COVID-19 pandemic impacted worldwide. The Basque Country was one of the regions in Spain most affected by the virus.

Methods: In this retrospective study, we took advantage of the Basque Health Service electronic health records data lake of over 20,000 deceased individuals, including 5000 positives for COVID-19, between 2020 and 2022 in Gipuzkoa (Basque Country, Spain).

Centenarians of the Basque Country are resilient to cancer.

Cancer is one of the leading causes of death and its prevalence increases with age. While centenarians exhibit extreme longevity and potential to avoid or delay aging-related diseases, their response to cancer is still barely explored. Our study took advantage of the Electronic Health Records to retrospectively compare the severity of cancer in centenarians (n = 649) and non-centenarians (n = 62,753) in the Basque Country (province of Gipuzkoa), Spain, through analyzing all the recorded diagnoses throughout their lifetime.

Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with and Activity in Neurodegenerative Diseases.

Herein, we describe the design, synthesis, and biological evaluation of 15 + hybrids. These ligands are polyfunctionalized indole derivatives developed by juxtaposing selected pharmacophoric moieties of and to act as multifunctional ligands. Compounds and were identified as potent HDAC6 inhibitors (IC = 0.

Centenarian hippocampus displays high levels of astrocytic metallothioneins.

The hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better quality of life, lower cognitive impairment, and reduced incidence of pathologies including neurodegenerative diseases.

Identification of a novel gene signature related to prognosis and metastasis in gastric cancer.

Background: Gastric Cancer (GC) presents poor outcome, which is consequence of the high incidence of recurrence and metastasis at early stages. GC patients presenting recurrent or metastatic disease display a median life expectancy of only 8 months. The mechanisms underlying GC progression remain poorly understood.

Physical Interventions Restore Physical Frailty and the Expression of CXCL-10 and IL-1β Inflammatory Biomarkers in Old Individuals and Mice.

Background: Frailty is a geriatric syndrome associated with negative health outcomes that represents a dynamic condition with a potential of reversibility after physical exercise interventions. Typically, inflammatory and senescence markers are increased in frail individuals. However, the impact that physical exercise exerts on inflammatory and senescence biomarkers remains unknown.

Development of Continuous Assessment of Muscle Quality and Frailty in Older Patients Using Multiparametric Combinations of Ultrasound and Blood Biomarkers: Protocol for the ECOFRAIL Study.

Background: Frailty resulting from the loss of muscle quality can potentially be delayed through early detection and physical exercise interventions. There is a demand for cost-effective tools for the objective evaluation of muscle quality, in both cross-sectional and longitudinal assessments. Literature suggests that quantitative analysis of ultrasound data captures morphometric, compositional, and microstructural muscle properties, while biological assays derived from blood samples are associated with functional information.

Empowering frail older adults: multicomponent elastic-band exercises and BCAA supplementation unleash physical health and preserve haematological biomarkers.

The effectiveness of Branched Chain Amino Acids (BCAAs) supplementation on enhancing exercise performance in both young and older adults remains a topic of debate. Recent research suggests that BCAAs combined with regular exercise might have an impact on human erythropoiesis, blood dynamics, and iron homeostasis. Given the increasing longevity of the global population, it is crucial to investigate the potential benefits of BCAA supplementation and regular exercise as non-pharmacological interventions for improving the overall health of frail older adults.

Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy.

Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-approved anti-anginal drug ranolazine (RANO) delays tumour recurrence with acquired BRAFi resistance.

Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals.

Background: Frailty is an intermediate and reversible geriatric syndrome that often precedes dependence. Therefore, its identification is essential to prevent dependence. Several molecules have been proposed as biomarkers of frailty, but none of them have reached clinical practice.

Current advances in temozolomide encapsulation for the enhancement of glioblastoma treatment.

Glioblastoma is the most common and lethal brain tumor in adults. The incorporation of temozolomide (TMZ) into the standard treatment has increased the overall survival rate of glioblastoma patients. Since then, significant advances have been made in understanding the benefits and limitations of TMZ.

KRT5/p63 Stem Cells Undergo Senescence in the Human Lung with Pathological Aging.

Adult lungs present high cellular plasticity against stress and injury, mobilizing stem/progenitor populations from conducting airways to maintain tissue homeostasis and gas exchange in alveolar spaces. With aging, pulmonary functional and structural deterioration occurs, mainly in pathological conditions, which is associated with impaired stem cell activity and increased senescence in mice. However, the impact of these processes underlying lung physiopathology in relation to aging has not been explored in humans.

High levels of HDAC expression correlate with microglial aging.

Background: Cellular damage gradually accumulates with aging, promoting a time-dependent functional decline of the brain. Microglia play an essential regulatory role in maintaining cognitive activity by phagocytosing cell debris and apoptotic cells during neurogenesis. The activities of different histone deacetylases (HDACs) regulate microglial function during development and neurodegeneration.

Senescence plays a role in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1; MIM #160900) is an autosomal dominant disorder, clinically characterized by progressive muscular weakness and multisystem degeneration. The broad phenotypes observed in patients with DM1 resemble the appearance of an accelerated aging process. However, the molecular mechanisms underlying these phenotypes remain largely unknown.

Norovirus Intestinal Infection and Lewy Body Disease in an Older Patient with Acute Cognitive Impairment.

We present a case report on an older woman with unspecific symptoms and predominant long-term gastrointestinal disturbances, acute overall health deterioration with loss of autonomy for daily activities, and cognitive impairment. Autopsy revealed the presence of alpha-synuclein deposits spread into intestinal mucosa lesions, enteric plexuses, pelvic and retroperitoneal nerves and ganglia, and other organs as well as Lewy pathology in the central nervous system (CNS). Moreover, we isolated norovirus from the patient, indicating active infection in the colon and detected colocalization of norovirus and alpha-synuclein in different regions of the patient's brain.

High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML.

Glioma stem cells (GSCs) are critical targets for glioma therapy. SOX9 is a transcription factor with critical roles during neurodevelopment, particularly within neural stem cells. Previous studies showed that high levels of SOX9 are associated with poor glioma patient survival.

Intrinsic role of chaperone-mediated autophagy in cancer stem cell maintenance.

Chaperone-mediated autophagy (CMA) is a selective type of autophagy specialized in the individual degradation of targeted proteins. Its impact in any cancer stem cell (CSC) subtype remained elusive. In a recent study, we characterized the expression of LAMP2A and CMA activity in glioblastoma revealing its enrichment in a glioma stem cell (GSC) subpopulation.

Impact of Cancer Stem Cells on Therapy Resistance in Gastric Cancer.

Gastric cancer (GC) is the fourth leading cause of cancer death worldwide, with an average 5-year survival rate of 32%, being of 6% for patients presenting distant metastasis. Despite the advances made in the treatment of GC, chemoresistance phenomena arise and promote recurrence, dissemination and dismal prognosis. In this context, gastric cancer stem cells (gCSCs), a small subset of cancer cells that exhibit unique characteristics, are decisive in therapy failure.

Targeting Myotonic Dystrophy Type 1 with Metformin.

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder of genetic origin. Progressive muscular weakness, atrophy and myotonia are its most prominent neuromuscular features, while additional clinical manifestations in multiple organs are also common. Overall, DM1 features resemble accelerated aging.

SOX9 Triggers Different Epithelial to Mesenchymal Transition States to Promote Pancreatic Cancer Progression.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers mainly due to spatial obstacles to complete resection, early metastasis and therapy resistance. The molecular events accompanying PDAC progression remain poorly understood. SOX9 is required for maintaining the pancreatic ductal identity and it is involved in the initiation of pancreatic cancer.