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Aging mitochondria

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https://www.readbyqxmd.com/read/30121784/thioredoxin-overexpression-in-both-the-cytosol-and-mitochondria-accelerates-age-related-disease-and-shortens-lifespan-in-male-c57bl-6-mice
#1
Geneva M Cunningham, Lisa C Flores, Madeline G Roman, Christie Cheng, Sara Dube, Colton Allen, Joseph M Valentine, Gene B Hubbard, Yidong Bai, Thomas L Saunders, Yuji Ikeno
To investigate the role of increased levels of thioredoxin (Trx) in both the cytosol (Trx1) and mitochondria (Trx2) on aging, we have conducted a study to examine survival and age-related diseases using male mice overexpressing Trx1 and Trx2 (TXNTg × TXN2Tg). Our study demonstrated that the upregulation of Trx in both the cytosol and mitochondria in male TXNTg × TXN2Tg C57BL/6 mice resulted in a significantly shorter lifespan compared to wild-type (WT) mice. Cross-sectional pathology data showed a slightly higher incidence of neoplastic diseases in TXNTg × TXN2Tg mice than WT mice...
August 18, 2018: GeroScience
https://www.readbyqxmd.com/read/30121730/variety-is-the-spice-of-life-how-to-explore-a-redox-dependent-heterogeneity-in-genomically-identical-cellular-populations
#2
Meytal Radzinski, Dana Reichmann
Cellular heterogeneity is a widespread phenomenon, existing across organisms and serving a crucial role in evolution and cell survival. Genetically identical cells may as a result present in a variety of forms with different gene and protein expressions, as well as oxidation level. As a result, a wide range of methodologies and techniques for dissecting different types of genetic, proteomic, and phenotypic heterogeneous traits have emerged in recent years in an effort to better understand how diversity exists within a single population and its effects therein...
August 18, 2018: Current Genetics
https://www.readbyqxmd.com/read/30116495/the-effect-of-mitoq-on-aging-related-biomarkers-a-systematic-review-and-meta-analysis
#3
REVIEW
Andrea J Braakhuis, Rohith Nagulan, Vaughan Somerville
Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years, particular focus has been put on mitochondria-targeted antioxidants, to decrease the concentration of reactive oxygen species and help alleviate the accumulation of oxidative damage and associated aging. MitoQ is a mitochondria-targeted antioxidant of which is reported to support healthy aging. The aim of this systematic review is to investigate the effects of MitoQ on oxidative outcomes related to the aging process...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/30116473/intracellular-and-intercellular-signalling-mechanisms-following-dna-damage-are-modulated-by-pink1
#4
Mihaela Temelie, Diana Iulia Savu, Nicoleta Moisoi
Impaired mitochondrial function and accumulation of DNA damage have been recognized as hallmarks of age-related diseases. Mitochondrial dysfunction initiates protective signalling mechanisms coordinated at nuclear level particularly by modulating transcription of stress signalling factors. In turn, cellular response to DNA lesions comprises a series of interconnected complex protective pathways, which require the energetic and metabolic support of the mitochondria. These are involved in intracellular as well as in extracellular signalling of damage...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/30111857/copd-is-accompanied-by-co-ordinated-transcriptional-perturbation-in-the-quadriceps-affecting-the-mitochondria-and-extracellular-matrix
#5
Saffron A G Willis-Owen, Anna Thompson, Paul R Kemp, Michael I Polkey, William O C M Cookson, Miriam F Moffatt, Samantha A Natanek
Skeletal muscle dysfunction is a frequent extra-pulmonary manifestation of Chronic Obstructive Pulmonary Disease (COPD) with implications for both quality of life and survival. The underlying biology nevertheless remains poorly understood. We measured global gene transcription in the quadriceps using Affymetrix HuGene1.1ST arrays in an unselected cohort of 79 stable COPD patients in secondary care and 16 healthy age- and gender-matched controls. We detected 1,826 transcripts showing COPD-related variation. Eighteen exhibited ≥2fold changes (SLC22A3, FAM184B, CDKN1A, FST, LINC01405, MUSK, PANX1, ANKRD1, C12orf75, MYH1, POSTN, FRZB, TNC, ACTC1, LINC00310, MYH3, MYBPH and AREG)...
August 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30108290/skeletal-muscle-mitochondrial-remodeling-in-exercise-and-diseases
#6
Zhenji Gan, Tingting Fu, Daniel P Kelly, Rick B Vega
Skeletal muscle fitness and plasticity is an important determinant of human health and disease. Mitochondria are essential for maintaining skeletal muscle energy homeostasis by adaptive re-programming to meet the demands imposed by a myriad of physiologic or pathophysiological stresses. Skeletal muscle mitochondrial dysfunction has been implicated in the pathogenesis of many diseases, including muscular dystrophy, atrophy, type 2 diabetes, and aging-related sarcopenia. Notably, exercise counteracts the effects of many chronic diseases on skeletal muscle mitochondrial function...
August 14, 2018: Cell Research
https://www.readbyqxmd.com/read/30107294/master-athletes-have-higher-mir-7-sirt3-and-sod2-expression-in-skeletal-muscle-than-age-matched-sedentary-controls
#7
Erika Koltai, Zoltan Bori, Peter Osvath, Ferenc Ihasz, Szablics Peter, Geza Toth, Hans Degens, Jörn Rittweger, Istvan Boldogh, Zsolt Radak
Regular physical exercise has health benefits and can prevent some of the ageing-associated muscle deteriorations. However, the biochemical mechanisms underlying this exercise benefit, especially in human tissues, are not well known. To investigate, we assessed this using miRNA profiling, mRNA and protein levels of anti-oxidant and metabolic proteins in the vastus lateralis muscle of master athletes aged over 65 years and age-matched controls. Master athletes had lower levels of miR-7, while mRNA or protein levels of SIRT3, SIRT1, SOD2, and FOXO1 levels were significantly higher in the vastus lateralis muscle of master athletes compared to muscles of age-matched controls...
August 7, 2018: Redox Biology
https://www.readbyqxmd.com/read/30104108/anti-oxidative-effects-of-17-%C3%AE-estradiol-and-genistein-in-human-skin-fibroblasts-and-keratinocytes
#8
Paola Savoia, Giulia Raina, Lara Camillo, Serena Farruggio, David Mary, Federica Veronese, Francesca Graziola, Elisa Zavattaro, Rossana Tiberio, Elena Grossini
BACKGROUND: Estrogens and phytoestrogens can hinder the aging process through mechanisms related to estrogen receptors (ERs), guanine nucleotide-binding protein-coupled receptor (GPER30), mitochondria function and nitric oxide (NO) release. Up to date, however, the above issues are a matter of debate. OBJECTIVE: To examine the effects elicited by 17 β-estradiol and genistein against peroxidation in human keratinocytes/fibroblasts and evaluate the role played by ERs, GPER30, mitochondria and NO...
August 6, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/30103670/autosomal-dominant-retinitis-pigmentosa-associated-gene-prpf8-is-essential-for-hypoxia-induced-mitophagy-through-regulating-ulk1-mrna-splicing
#9
Guang Xu, Ting Li, Jiayi Chen, Changyan Li, Haixin Zhao, Chengcheng Yao, Hua Dong, Kaiqing Wen, Kai Wang, Jie Zhao, Qing Xia, Tao Zhou, Huafeng Zhang, Ping Gao, Ailing Li, Xin Pan
Aged and damaged mitochondria can be selectively degraded by specific autophagic elimination, termed mitophagy. Defects in mitophagy have been increasingly linked to several diseases including neurodegenerative diseases, metabolic diseases and other aging-related diseases. However, the molecular mechanisms of mitophagy are not fully understood. Here, we identify PRPF8 (pre-mRNA processing factor 8), a core component of the spliceosome, as an essential mediator in hypoxia-induced mitophagy from an RNAi screen based on a fluorescent mitophagy reporter, mt-Keima...
August 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30102730/the-effect-of-tmem135-overexpression-on-the-mouse-heart
#10
Sarah Aileen Lewis, Tetsuya Takimoto, Shima Mehrvar, Hitoshi Higuchi, Anna-Lisa Doebley, Giangela Stokes, Nader Sheibani, Sakae Ikeda, Mahsa Ranji, Akihiro Ikeda
Tissues with high-energy demand including the heart are rich in the energy-producing organelles, mitochondria, and sensitive to mitochondrial dysfunction. While alterations in mitochondrial function are increasingly recognized in cardiovascular diseases, the molecular mechanisms through which changes in mitochondria lead to heart abnormalities have not been fully elucidated. Here, we report that transgenic mice overexpressing a novel regulator of mitochondrial dynamics, transmembrane protein 135 (Tmem135), exhibit increased fragmentation of mitochondria and disease phenotypes in the heart including collagen accumulation and hypertrophy...
2018: PloS One
https://www.readbyqxmd.com/read/30099751/a-cellular-mechanism-of-muscle-memory-facilitates-mitochondrial-remodelling-following-resistance-training
#11
Hojun Lee, Kijeong Kim, Boa Kim, Junchul Shin, Sudarsan Rajan, Jingwei Wu, Xiongwen Chen, Michael D Brown, Sukho Lee, Joon-Young Park
KEY POINTS: Referring to the muscle memory theory, previously trained muscles acquire strength and volume much faster than naive muscles. Using extreme experimental models such as synergist ablation or steroid administration, previous studies have demonstrated that the number of nuclei increases when a muscle becomes enlarged, which serves as a cellular muscle memory mechanism for the muscle. In the present study, we found that, when rats were subjected to physiologically relevant resistance training, the number of myonuclei increased and was retained during a long-term detraining period...
August 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/30098187/ultrastructural-morphology-of-the-optic-nerve-head-in-aged-and-glaucomatous-mice
#12
Ying Zhu, Anthony C Pappas, Rui Wang, Philip Seifert, Daniel Sun, Tatjana C Jakobs
Purpose: To study age- and intraocular pressure-induced changes in the glial lamina of the murine optic nerve on the ultrastructural level. Methods: Naïve C57bl/6 mice at various ages spanning the time between early adulthood (3 months) and senescence (30 months) were used in this study. In addition, the intraocular pressure (IOP) was increased in a group of young mice by injection of microbeads into the anterior chamber. The unmyelinated segments of the optic nerve containing the glial lamina were prepared for transmission electron microscopy and imaged at high resolution...
August 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/30096848/mitochondria-targeted-antioxidants-and-skeletal-muscle-function
#13
REVIEW
Sophie C Broome, Jonathan S T Woodhead, Troy L Merry
One of the main sources of reactive oxygen species (ROS) in skeletal muscle is the mitochondria. Prolonged or very high ROS exposure causes oxidative damage, which can be deleterious to muscle function, and as such, there is growing interest in targeting antioxidants to the mitochondria in an effort to prevent or treat muscle dysfunction and damage associated with disease and injury. Paradoxically, however, ROS also act as important signalling molecules in controlling cellular homeostasis, and therefore caution must be taken when supplementing with antioxidants...
August 8, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/30096432/the-autophagic-response-to-oxidative-stress-in-osteoarthritic-chondrocytes-is-deregulated
#14
Andreas Goutas, Christina Syrrou, Ioanna Papathanasiou, Aspasia Tsezou, Varvara Trachana
It has been reported that oxidative stress (OS) is involved in the pathogenesis of osteoarthritis (OA) and that defective autophagy is accompanying this age-related disease. Moreover, it has been proposed that induction of autophagy could serve as therapeutic mean, as it was shown to alleviate several symptoms in OA animal models. On the contrary, it is also known that autophagic death, which results from over-activation of autophagy, is also a contributor in the development of this disease. Given this discrepancy, in this study we aimed at analysing the autophagic response against acute exogenous oxidative insult of chondrocytes from healthy individuals (control) and OA patients (OA)...
August 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30094760/respirometric-reserve-capacity-of-cumulus-cell-mitochondria-correlates-with-oocyte-maturity
#15
Sharon H Anderson, Michael J Glassner, Andrey Melnikov, Gary Friedman, Zulfiya Orynbayeva
PURPOSE: Oocyte competence is critical in success of assisted reproduction. Metabolic signaling between oocyte and cumulus cells within the cumulus-oocyte complex procure oocyte development. This study evaluated the relationship between respirometric activity of cumulus cells and maturity of corresponding oocytes. METHODS: In prospective cohort study, 20 women of age 28-42 undergoing IVF procedure were involved. To evaluate oocyte maturity, the cumulus cells from individual oocytes were assessed flow cytometrically by double labeling of cells with mitochondria specific dyes...
August 9, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/30094600/inhibition-of-mitophagy-decreases-survival-of-caenorhabditis-elegans-by-increasing-protein-aggregation
#16
Mehtap Civelek, Jan-Frederik Mehrkens, Nora-Maria Carstens, Elena Fitzenberger, Uwe Wenzel
Autophagy of mitochondria, i.e., mitophagy, plays a crucial role in coping with stressors in the aging process, metabolic disturbances, and neurological disorders. Impairments of the process might consequently lead to enhanced accumulation of aged and aggregated proteins and reduced cellular integrity in response to stress. In the present study, we used the stress-sensitive mutant mev-1 of Caenorhabditis elegans to assess the effects of the knockdown of mitophagy relevant genes on survival under heat stress, the amount of autophagosomes, and on protein aggregation...
August 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/30092361/the-role-of-melatonin-a-multitasking-molecule-in-retarding-the-processes-of-ageing
#17
REVIEW
Maryam Majidinia, Russel J Reiter, Seyed Kazem Shakouri, Bahman Yousefi
Biological ageing is generally accompanied by a gradual loss of cellular functions and physiological integrity of organ systems, the consequential enhancement of vulnerability, senescence and finally death. Mechanisms which underlie ageing are primarily attributed to an array of diverse but related factors including free radical-induced damage, dysfunction of mitochondria, disruption of circadian rhythms, inflammaging, genomic instability, telomere attrition, loss of proteostasis, deregulated sensing of nutrients, epigenetic alterations, altered intercellular communication, and decreased capacity for tissue repair...
August 6, 2018: Ageing Research Reviews
https://www.readbyqxmd.com/read/30090653/pkc%C3%AE-activation-is-involved-in-ros-mediated-mitochondrial-dysfunction-and-apoptosis-in-cardiomyocytes-exposed-to-advanced-glycation-end-products-ages
#18
Yao-Chih Yang, Cheng-Yen Tsai, Chien-Lin Chen, Chia-Hua Kuo, Chien-Wen Hou, Shi-Yann Cheng, Ritu Aneja, Chih-Yang Huang, Wei-Wen Kuo
Diabetic patients exhibit serum AGE accumulation, which is associated with reactive oxygen species (ROS) production and diabetic cardiomyopathy. ROS-induced PKCδ activation is linked to mitochondrial dysfunction in human cells. However, the role of PKCδ in cardiac and mitochondrial dysfunction caused by AGE in diabetes is still unclear. AGE-BSA-treated cardiac cells showed dose- and time-dependent cell apoptosis, ROS generation, and selective PKCδ activation, which were reversed by NAC and rotenone. Similar tendency was also observed in diabetic and obese animal hearts...
August 2018: Aging and Disease
https://www.readbyqxmd.com/read/30089816/mitochondrial-dna-m-3243a-g-heteroplasmy-affects-multiple-aging-phenotypes-and-risk-of-mortality
#19
Gregory J Tranah, Shana M Katzman, Kevin Lauterjung, Kristine Yaffe, Todd M Manini, Stephen Kritchevsky, Anne B Newman, Tamara B Harris, Steven R Cummings
Mitochondria contain many copies of a circular DNA molecule (mtDNA), which has been observed as a mixture of normal and mutated states known as heteroplasmy. Elevated heteroplasmy at a single mtDNA site, m.3243A > G, leads to neurologic, sensory, movement, metabolic, and cardiopulmonary impairments. We measured leukocyte mtDNA m.3243A > G heteroplasmy in 789 elderly men and women from the bi-racial, population-based Health, Aging, and Body Composition Study to identify associations with age-related functioning and mortality...
August 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30089732/human-adipose-beiging-in-response-to-cold-and-mirabegron
#20
Brian S Finlin, Hasiyet Memetimin, Amy L Confides, Ildiko Kasza, Beibei Zhu, Hemendra J Vekaria, Brianna Harfmann, Kelly A Jones, Zachary R Johnson, Philip M Westgate, Caroline M Alexander, Patrick G Sullivan, Esther E Dupont-Versteegden, Philip A Kern
BACKGROUND: The induction of beige adipocytes in s.c. white adipose tissue (WAT) depots of humans is postulated to improve glucose and lipid metabolism in obesity. The ability of obese, insulin-resistant humans to induce beige adipose tissue is unknown. METHODS: We exposed lean and obese research participants to cold (30-minute ice pack application each day for 10 days of the upper thigh) or treated them with the β3 agonist mirabegron. We determined beige adipose marker expression by IHC and quantitative PCR, and we analyzed mitochondrial bioenergetics and UCP activity with an Oxytherm system...
August 9, 2018: JCI Insight
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