The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches.

The biological process of aging is influenced by a complex interplay of genetic, environmental, and epigenetic factors. Recent advancements in the fields of epigenetics and senolytics offer promising avenues for understanding and addressing age-related diseases. Epigenetics refers to heritable changes in gene expression without altering the DNA sequence, with mechanisms like DNA methylation, histone modification, and non-coding RNA regulation playing critical roles in aging.

Grafts of hydrogel-embedded electrically stimulated subventricular stem cells into the stroke cavity improves functional recovery of mice.

The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia. One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area. However, only a small percentage of these neurons survive, and many do not reach the damaged area, possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.

Biomarkers of cognitive and memory decline in psychotropic drug users.

Psychotropic drugs are vital in psychiatry, aiding in the management of mental health disorders. Their use requires an understanding of their pharmacological properties, therapeutic applications, and potential side effects. Ongoing research aims to improve their efficacy and safety.

Translatability of life-extending pharmacological treatments between different species.

Anti-aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti-aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti-aging treatments to human applications presents a considerable challenge.

Pharmacological and stem cell therapy of stroke in animal models: Do they accurately reflect the response of humans?

Cerebrovascular diseases are the second leading cause of death worldwide. Despite significant research investment, the only available therapeutic options are mechanical thrombectomy and tissue plasminogen activator thrombolysis. None of the more than a thousand drugs tested on animal models have proven successful in human clinical trials.

Knockdown of NEAT1 prevents post-stroke lipid droplet agglomeration in microglia by regulating autophagy.

Background: Lipid droplets (LD), lipid-storing organelles containing neutral lipids like glycerolipids and cholesterol, are increasingly accepted as hallmarks of inflammation. The nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA with over 200 nucleotides, exerts an indispensable impact on regulating both LD agglomeration and autophagy in multiple neurological disorders. However, knowledge as to how NEAT1 modulates the formation of LD and associated signaling pathways is limited.

TGF-β1 Decreases Microglia-Mediated Neuroinflammation and Lipid Droplet Accumulation in an In Vitro Stroke Model.

ypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-β1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation.

TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke.

Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation.

Stroke stimulates reactive astrogliosis, aquaporin 4 (AQP4) depolarization and neuroinflammation. Preconditioned extracellular vesicles (EVs) from microglia exposed to hypoxia, in turn, reduce poststroke brain injury. Nevertheless, the underlying mechanisms of such effects are elusive, especially with regards to inflammation, AQP4 polarization, and cerebrospinal fluid (CSF) flow.

Emerging roles of extracellular vesicle-associated non-coding RNAs in hypoxia: Insights from cancer, myocardial infarction and ischemic stroke.

Hypoxia is a central pathophysiological component in cancer, myocardial infarction and ischemic stroke, which represent the most common medical conditions resulting in long-term disability and death. Recent evidence suggests common signaling pathways in these diverse settings mediated by non-coding RNAs (ncRNAs), which are packaged in extracellular vesicles (EVs) protecting ncRNAs from degradation. EVs are a heterogeneous group of lipid bilayer-covered vesicles released from virtually all cells, which have important roles in intercellular communication.

Mitral valve calcification as an index of left ventricular dysfunction in patients with end-stage renal disease on peritoneal dialysis.

To determine whether mitral valve or anulus calcification (MC) in patients with end-stage renal disease is associated with abnormalities of left ventricular (LV) structure and function, cardiac characteristics of 55 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with (n = 26; age: 59 +/- 10 years) vs without (n = 29; age: 58 +/- 12 years) MC were analyzed using echocardiography and Doppler echocardiography. Sclerosis of the mitral valve anulus was detected in 18 (7 women, 11 men; age: 58 +/- 10 years) patients, sclerosis of mitral valve leaflets in 24 (13 women, 9 men; age: 59 +/- 10 years) patients. Patients with MC had higher systolic arterial blood pressure before initiation of dialysis therapy (191/104 mm Hg vs 173/94 mm Hg; p < 0.

Course of left ventricular diastolic dysfunction in end-stage renal disease on long-term continuous ambulatory peritoneal dialysis.

To determine factors contributing to abnormal left ventricular (LV) diastolic filling in patients on long-term continuous ambulatory peritoneal dialysis (CAPD), 11 (age: 55 +/- 13 years; CAPD duration: 33 +/- 32 months) out of 42 originally studied CAPD patients were followed over 35 months with echocardiography and pulsed Doppler echocardiography. LV dimensions and systolic function remained normal. Doppler parameters indicated diastolic LV dysfunction in 9/11 patients in the initial study.

Predictive value of mitral and aortic valve sclerosis for survival in end-stage renal disease on continuous ambulatory peritoneal dialysis.

To determine whether mitral valve or anular sclerosis or calcification (MC) is associated with reduced survival in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD), 53 CAPD patients were followed with echocardiography and Doppler echocardiography over 35 months. Both nonsurvivors and survivors with MC had higher systolic blood pressure before CAPD and calcium-phosphorus products during CAPD treatment than patients without MC (p < 0.05).

Course of left ventricular hypertrophy and function in end-stage renal disease after renal transplantation.

Cardiovascular complications are frequent and related to left ventricular (LV) hypertrophy and dysfunction in end-stage renal disease. To examine cardiac changes after renal transplantation, 24 hemodialysis patients (18 men and 6 women, age 47 +/- 12 years) were analyzed in a prospective follow-up study with echocardiography immediately before and 41 +/- 30 months after renal transplantation. Mean systolic blood pressure (hemodialysis vs transplantation: 156 +/- 35 vs 144 +/- 15 mm Hg; p = not significant [NS]), as averages of 6 measurements from 2 weeks, remained constant and elevated.

Diastolic left ventricular function after renal transplantation in patients with normal and hypertrophied myocardium.

While diastolic left ventricular (LV) dysfunction is frequent and associated with cardiovascular complications in end-stage renal disease treated with dialysis, controversial information exists on diastolic LV function after renal transplantation. Therefore, Doppler echocardiographic parameters of LV diastolic filling were analyzed in 17 transplanted patients with normal LV mass (< 150 g/m2; mean: 128 +/- 17 g/m2) and 24 transplanted patients with LV hypertrophy (> 150 g/m2; mean: 197 +/- 36 g/m2) and compared with 28 normal controls without and 11 controls with LV hypertrophy. Mean age (normal vs.

Progression of valvular sclerosis in end-stage renal disease treated by long-term peritoneal dialysis.

While patients with end-stage renal disease treated by intermittent hemodialysis have frequent and progressive valve disease, nothing is known of the prevalence and course of valvular abnormalities in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Therefore, valves of 24 CAPD patients (ages 55 +/- 11 years; CAPD duration: 29 +/- 28 months) were studied in a prospective echocardiographic and Doppler echocardiographic follow-up analysis over 35 months. Most frequent findings were sclerosis of the aortic annulus (100% at both assessments) and of the anterior mitral valve leaflet (first vs.

Progression of left ventricular hypertrophy in end-stage renal disease treated by continuous ambulatory peritoneal dialysis depends on hypertension and hypercirculation.

To determine whether obvious hemodynamic advantages of continuous ambulatory peritoneal dialysis (CAPD) over intermittent hemodialysis are reflected in superior cardiac structure and function, 16 of 55 analyzed CAPD patients (CAPD duration: 28 months) were followed over 35 months with echocardiography in a prospective analysis: 26 patients had died. LV dimensions (end-diastolic: 52 +/- 7 vs. 51 +/- 8 mm; control vs.

Cardiovascular factors influencing survival in end-stage renal disease treated by continuous ambulatory peritoneal dialysis.

To determine whether hemodynamic advantages of continuous ambulatory peritoneal dialysis (CAPD) over intermittent hemodialysis are associated with improved survival and identify cardiac risk factors for early death, 55 patients on CAPD (age 58 +/- 11 years; CAPD duration: 29 +/- 25 months) were followed in a noninvasive prospective analysis over 35 months. At follow-up, 25 patients had died; 16 deaths were related to cardiovascular causes. Nonsurvivors were older (62 +/- 8 vs 55 +/- 12 years; p less than 0.