mitochondrial and aging

Once considered passive cells of the central nervous system (CNS), glia are now known to actively maintain the CNS parenchyma; in recent years, the evidence for glial functions in CNS physiology and pathophysiology has only grown. Astrocytes, a heterogeneous group of glial cells, play key roles in regulating the metabolic and inflammatory landscape of the CNS and have emerged as potential therapeutic targets for a variety of disorders. This review will outline astrocyte functions in the CNS in healthy ageing, obesity, and neurodegeneration, with a focus on the inflammatory responses and mitochondrial function, and will address therapeutic outlooks...

Perilipin 2 (PLIN2) is a lipid droplet (LD)-coating protein playing important roles in lipid homeostasis and suppression of lipotoxicity in different tissues and cell types. Recently, a role for PLIN2 in supporting mitochondrial function has emerged. PLIN2 dysregulation is involved in many metabolic disorders and age-related diseases. However, the exact consequences of PLIN2 dysregulation are not yet completely understood. In this study, we knocked down (KD) PLIN2 in primary human dermal fibroblasts (hDFs) from young (mean age 29 years) and old (mean age 71 years) healthy donors...

We aimed to investigate the relationship between superoxide dismutase 2-related oxidative stress in the paraspinal muscles and spinal alignment, clinical skeletal muscle parameters, and mitochondrial function. Multifidus muscle samples from patients who underwent posterior lumbar surgery were analyzed. Patients with diseases affecting oxidative stress and spinal alignment were excluded. The superoxide dismutase 2 redox index was defined as the ratio of reactive oxygen species (superoxide) to antioxidant enzymes (superoxide dismutase 2) and was used as an index of oxidative stress...

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs...

Cardiovascular disease is a leading cause of morbidity and mortality, and exercise-training (TRN) is known to reduce risk factors and protect the heart from ischemia and reperfusion injury. Though the cardioprotective effects of exercise are well-documented, underlying mechanisms are not well understood. This review highlights recent findings and focuses on cardiac factors with emphasis on K+ channel control of the action potential duration (APD), β-adrenergic and adenosine regulation of cardiomyocyte function, and mitochondrial Ca2+ regulation...

BACKGROUND: Mutations in mitochondrial tRNA (mt-tRNA) could be the origin of some type 2 diabetes mellitus (T2DM) cases, but the mechanism remained largely unknown. AIM: The aim of this study was to assess the impact of a novel mitochondrial tRNACys /tRNATyr A5826G mutation on the development and progression of T2DM. METHODS: A four-generation Han Chinese family with maternally inherited diabetes underwent clinical, genetic and biochemical analyses...

Ergothioneine (EGT) is a diet-derived, atypical amino acid that accumulates to high levels in human tissues. Reduced EGT levels have been linked to age-related disorders, including neurodegenerative and cardiovascular diseases, while EGT supplementation is protective in a broad range of disease and aging models in mice. Despite these promising data, the direct and physiologically relevant molecular target of EGT has remained elusive. Here we use a systematic approach to identify how mitochondria remodel their metabolome in response to exercise training...

UNLABELLED: The mitochondrial-rich renal tubule cells are key regulators of blood homeostasis via excretion and reabsorption of metabolic waste. With age, tubules are subject to increasing mitochondrial dysfunction and declining nicotinamide adenine dinucleotide (NAD + ) levels, both hampering ATP production efficiency. We tested two mitochondrial interventions in young (6-mo) and aged (26-mo) adult male mice: elamipretide (ELAM), a tetrapeptide in clinical trials that improves mitochondrial structure and function, and nicotinamide mononucleotide (NMN), an NAD + intermediate and commercially available oral supplement...

Leber's hereditary optic atrophy (LHON) is a genetic optic neuropathy that is more prevalent in young males but can occur from childhood to old age. The primary cause is mitochondrial genetic mutations, which are associated with dysfunction of mitochondrial electron transport chain complex I. It manifests as acute to subacute visual impairment, often starting unilaterally but progressing to involve both eyes within weeks to months. Visual loss is severe, with many patients having corrected visual acuity below 0...

Disrupted mitochondrial dynamics and mitophagy contribute to functional deterioration of skeletal muscle (SM) during aging, but the regulatory mechanisms are poorly understood. Our previous study demonstrated that the expression of thyroid hormone receptor α (TRα) decreased significantly in aged mice, suggesting that the alteration of thyroidal elements, especially the decreased TRα, might attenuate local THs action thus to cause the degeneration of SM with aging, while the underlying mechanism remains to be further explored...

The human mitochondrial DNA polymerase gamma is a holoenzyme, involved in mitochondrial DNA (mtDNA) replication and maintenance, composed of a catalytic subunit (POLG) and a dimeric accessory subunit (POLG2) conferring processivity. Mutations in POLG or POLG2 cause POLG-related diseases in humans, leading to a subset of Mendelian-inherited mitochondrial disorders characterized by mtDNA depletion (MDD) or accumulation of multiple deletions, presenting multi-organ defects and often leading to premature death at a young age...

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BACKGROUND: p66Shc, as a redox enzyme, regulates reactive oxygen species (ROS) production in mitochondria and autophagy. However, the mechanisms by which p66Shc affects autophagosome formation are not fully understood. METHODS: p66Shc expression and its location in the trophoblast cells were detected in vivo and in vitro. Small hairpin RNAs or CRISPR/Cas9, RNA sequencing, and confocal laser scanning microscope were used to clarify p66Shc's role in regulating autophagic flux and STING activation...

Lactobacillus fermentum can exert antiaging effects, but their roles are strain-specific, and little is known about the molecular mechanisms in some strains. This study investigated the antiaging effects of L. fermentum WC2020 (WC2020) isolated from Chinese fermented pickles and the underlying mechanism of the action in Caenorhabditis elegans. WC2020 enhanced the mean lifespan of L1-stage and L4-stage worms by 22.67% and 12.42%, respectively, compared with Escherichia coli OP50 (OP50), a standard food source for C...

BACKGROUND: Helsmoortel-Van der Aa syndrome is a neurodevelopmental disorder in which patients present with autism, intellectual disability, and frequent extra-neurological features such as feeding and gastrointestinal problems, visual impairments, and cardiac abnormalities. All patients exhibit heterozygous de novo nonsense or frameshift stop mutations in the Activity-Dependent Neuroprotective Protein (ADNP) gene, accounting for a prevalence of 0.2% of all autism cases worldwide. ADNP fulfills an essential chromatin remodeling function during brain development...

Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death (PCD)-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds...

Osteoarthritis (OA) is a prevalent degenerative condition commonly observed in the elderly, leading to consequential disability. Despite notable advancements made in clinical strategies for OA, its pathogenesis remains uncertain. The intricate association between OA and metabolic processes has yet to receive comprehensive exploration. In our investigation, we leveraged public databases and applied machine learning algorithms, including WGCNA, LASSO, RF, immune infiltration analysis, and pathway enrichment analysis, to scrutinize the role of lipid metabolism-associated genes (LAGs) in the OA...

Effective therapeutic interventions for elderly patients are lacking, despite advances in pharmacotherapy. Methylated urolithin A (mUro A), a modified ellagitannin (ET)-derived metabolite, exhibits anti-inflammatory, antioxidative, and anti-apoptotic effects. Current research has primarily investigated the neuroprotective effects of mUroA in aging mice and explored the underlying mechanisms. Our study used an in vivo aging model induced by D-galactose (D-gal) to show that mUro A notably improved learning and memory, prevented synaptic impairments by enhancing synaptic protein expression and increasing EPSCs, and reduced oxidative damage in aging mice...

Atherosclerosis, an immunoinflammatory disease of medium and large arteries, is associated with life-threatening clinical events, such as acute coronary syndromes and stroke. Chronic inflammation and impaired lipoprotein metabolism are considered to be among the leading causes of atherosclerosis, while numerous risk factors, including arterial hypertension, diabetes mellitus, obesity, and aging, can contribute to the development of the disease. In recent years, emerging evidence has underlined the key role of mitochondrial dysfunction in the pathogenesis of atherosclerosis...

Our objective was to understand how maternal age influences the mitochondrial population and ATP content of in vivo matured bovine oocytes. We hypothesized that in vivo matured oocytes from older cows would have altered mitochondrial number and distribution patterns and lower cytoplasmic ATP content compared to the oocytes obtained from younger cows. Follicles ≥5mm were ablated in old cows (13 to 22 yrs, Old Group, n = 7) and their younger daughters (4 to 10 years old, Young Group; n = 7) to induce the emergence of a new follicular wave...