A5083523538- Telomeres, Telomerase, and Senescence
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Circadian rhythm and melatonin
- Autophagy in Disease and Therapy
- Nitric Oxide and Endothelin Effects
- Pancreatic function and diabetes
- Sirtuins and Resveratrol in Medicine
- Peroxisome Proliferator-Activated Receptors
- Frailty in Older Adults
- Physiological and biochemical adaptations
- Erythrocyte Function and Pathophysiology
- Skin Protection and Aging
- Cardiac Valve Diseases and Treatments
- RNA regulation and disease
- Calcium signaling and nucleotide metabolism
- Epilepsy research and treatment
- Redox biology and oxidative stress
- Coenzyme Q10 studies and effects
- Tea Polyphenols and Effects
- Glioma Diagnosis and Treatment
- Cardiovascular Function and Risk Factors
- Ion channel regulation and function
Newcastle Hospitals - Campus for Ageing and Vitality
2014-2025
Newcastle University
2016-2025
Alcyomics (United Kingdom)
2021-2024
University of Newcastle Australia
2012-2022
Helix (United States)
2021
Mayo Clinic
2021
Kyoto University
1979-2012
MRC Mitochondrial Biology Unit
2003-2010
Hokkaido University
1987-2006
MRC Human Nutrition Research
2003-2005
Abstract The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state irreversible cell-cycle arrest combined the secretion proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute age-related tissue degeneration. Here we show that accumulation senescent promotes hepatic fat steatosis. We report close correlation between markers hepatocyte senescence. elimination by suicide gene-meditated ablation p16 Ink4a...
Cell senescence is an important tumour suppressor mechanism and driver of ageing. Both functions are dependent on the development senescent phenotype, which involves overproduction pro-inflammatory pro-oxidant signals. However, exact mechanisms regulating these phenotypes remain poorly understood. Here, we show critical role mitochondria in cellular senescence. In multiple models senescence, absence reduced a spectrum effectors while preserving ATP production via enhanced glycolysis. Global...
Summary In senescent cells, a DNA damage response drives not only irreversible loss of replicative capacity but also production and secretion reactive oxygen species (ROS) bioactive peptides including pro‐inflammatory cytokines. This makes cells potential cause tissue functional decline in aging. To our knowledge, we show here for the first time evidence suggesting that induces senescence‐like state mature postmitotic neurons vivo . About 40–80% Purkinje 20–40% cortical, hippocampal...
Abstract Senescent cells accumulate with age in multiple tissues and may cause age‐associated disease functional decline. In vitro, senescent induce senescence bystander cells. To see how important this effect be for accumulation of vivo, we xenotransplanted into skeletal muscle skin immunocompromised NSG mice. 3 weeks after the last transplantation, mouse dermal fibroblasts myofibres displayed markers vicinity transplanted cells, but not where non‐senescent or no were injected. Adjacent to...
Mitochondrial function is an important determinant of the ageing process; however, mitochondrial properties that enable longevity are not well understood. Here we show optimal assembly complex I predicts in mice. Using unbiased high-coverage high-confidence approach, demonstrate electron transport chain proteins, especially matrix arm subunits I, decreased young long-living mice, which associated with improved assembly, higher I-linked state 3 oxygen consumption rates and superoxide...
Although the physiological role of uncoupling proteins (UCPs) 2 and 3 is uncertain, their activation by superoxide lipid peroxidation products suggest that UCPs are central to mitochondrial response reactive oxygen species. We examined whether such as 4-hydroxy-2-trans-nonenal act independently activate UCPs, or if they share a common pathway, perhaps exposure leading formation products. This possibility can be tested blocking putative species cascade with selective antioxidants then...
Kinetic refolding reactions of ferricytochrome c and beta-lactoglobulin have been studied by stopped-flow circular dichroism monitoring rapid ellipticity changes peptide backbone side-chain chromophores. In both proteins, a transient intermediate accumulates within the dead time mixing (18 ms), has an appreciable amount secondary structure but possesses unfolded tertiary structure. It is suggested that formation framework in protein folding common property observed variety globular proteins.
Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, the molecular etiology remains undiagnosed in majority of cases. Through whole-exome sequencing, we identified recessive nonsense splicing mutations FBXL4 segregating three unrelated consanguineous kindreds which affected children present with a fatal encephalopathy, lactic acidosis, severe mtDNA muscle. We show that is an F-box protein colocalizes mitochondria loss-of-function...
Abstract Objective Superoxide dismutase 2 (SOD2) is down‐ regulated in osteoarthritis (OA). This study was undertaken to investigate the functional effects of this down‐regulation context oxidative damage and mitochondrial dysfunction. Methods Lipid peroxidation articular cartilage from OA patients lesion‐free control subjects with femoral neck fracture assessed by measuring malondialdehyde levels using thiobarbituric acid reactive substances assay. Long‐range polymerase chain reaction...
The telomerase reverse transcriptase protein TERT has recently been demonstrated to have a variety of functions both in vitro and vivo , which are distinct from its canonical role telomere extension. In different cellular systems, shown be protective through interaction with mitochondria. previously found rodent neurons, we hypothesize that it might function adult human brain. Here, investigated the expression at stages Alzheimer's disease pathology (Braak Stages I-VI) situ ability protect...
Aging | doi:10.18632/aging.100196. Chunfang Wang, Mandy Maddick, Satomi Miwa, Diana Jurk, Rafal Czapiewski, Gabriele Saretzki, Sabine A.S. Langie, Roger W.L. Godschalk, Kerry Cameron, Thomas von Zglinicki
Abstract Neural activity is tightly coupled to energy consumption, particularly sugars such as glucose. However, we find that, unlike mature neurons and astrocytes, neural stem/progenitor cells (NSPCs) do not require glucose sustain aerobic respiration. NSPCs within the adult subventricular zone (SVZ) express enzymes required for fatty acid oxidation show sustained increases in oxygen consumption upon treatment with a polyunsaturated acid. also demonstrate decreases etomoxir, an inhibitor of...
Inhibition of monocarboxylate transporter 1 has been proposed as a therapeutic approach to perturb lactate shuttling in tumor cells that lack 4. We examined the inhibitor AZD3965, currently phase I clinical studies, potential therapy for diffuse large B-cell lymphoma and Burkitt lymphoma. Whilst extensive protein was found 120 10 patients' tumors, 4 expression undetectable 73% samples or negligible each sample. AZD3965 treatment led rapid accumulation intracellular panel cell lines with low...
Amplex Red is a fluorescent probe that widely used to detect hydrogen peroxide (H2O2) in reaction where it oxidised resorufin by horseradish peroxidase (HRP) as catalyst. This assay highly rated amongst other similar probes thanks its superior sensitivity and stability. However, we report here readily converted carboxylesterase without requiring H2O2, or oxygen: this seen various tissue samples such liver kidney well cultured cells, causing serious distortion of H2O2 measurements. The can be...
Autophagy is an essential catabolic process that promotes the clearance of surplus or damaged intracellular components. Loss autophagy in age-related human pathologies contributes to tissue degeneration through a poorly understood mechanism. Here, we identify evolutionarily conserved role from yeast humans preservation nicotinamide adenine dinucleotide (NAD) levels, which are critical for cell survival. In respiring mouse fibroblasts with deficiency, loss mitochondrial quality control was...