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Aging mitochondria

Leena Habiballa, Hanna Salmonowicz, João F Passos
Musculoskeletal ageing and its associated diseases are major contributors to the loss of independence and reduced quality of life in older people. Several recent studies indicate that cellular senescence is a contributor to age-related loss of function in various organs including muscle, bones and joints. Importantly, these studies indicate that therapies targeting specifically senescent cells have great therapeutic potential in improving musculoskeletal health during ageing. Senescent cells are characterised by dramatic changes in mitochondrial function, metabolism and homeostasis...
October 15, 2018: Free Radical Biology & Medicine
R Hartman, P Patil, R Tisherman, C St Croix, L J Niedernhofer, P D Robbins, F Ambrosio, B Van Houten, G Sowa, N Vo
Robust cellular bioenergetics is vital in the energy-demanding process of maintaining matrix homeostasis in the intervertebral disc. Age-related decline in disc cellular bioenergetics is hypothesised to contribute to the matrix homeostatic perturbation observed in intervertebral disc degeneration. The present study aimed to measure how ageing impacted disc cell mitochondria and bioenergetics. Age-related changes measured included matrix content and cellularity in disc tissue, as well as matrix synthesis, cell proliferation and senescence markers in cell cultures derived from annulus fibrosus (AF) and nucleus pulposus (NP) isolated from the discs of young (6-9 months) and older (36-50 months) New Zealand White rabbits...
October 18, 2018: European Cells & Materials
Takae Kiyama, Ching-Kang Chen, Steven W Wang, Ping Pan, Zhenlin Ju, Jing Wang, Shinako Takada, William H Klein, Chai-An Mao
BACKGROUND: Mitochondrial dysfunction has been implicated in the pathologies of a number of retinal degenerative diseases in both the outer and inner retina. In the outer retina, photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and sensitivity to oxidative stress. However, it is unclear how defective mitochondrial biogenesis affects neural development and contributes to neural degeneration. In this report, we investigated the in vivo function of nuclear respiratory factor 1 (Nrf1), a major transcriptional regulator of mitochondrial biogenesis in both proliferating retinal progenitor cells (RPCs) and postmitotic rod photoreceptor cells (PRs)...
October 17, 2018: Molecular Neurodegeneration
Sonali Nashine, Pinchas Cohen, Anthony B Nesburn, Baruch D Kuppermann, M Cristina Kenney
Mitochondrial-derived peptides (MDPs) are rapidly emerging therapeutic targets to combat development of neurodegenerative diseases. SHLP2 (small humanin-like peptide 2) is a newly discovered MDP that is coded from the MT-RNR2 (Mitochondrially encoded 16S rRNA) gene in mitochondrial DNA (mtDNA). In the current study, we examined the biological consequences of treatment with exogenously-added SHLP2 in an in vitro human transmitochondrial age-related macular degeneration (AMD) ARPE-19 cell model. In AMD cells, we observed significant down-regulation of the MDP-coding MT-RNR2 gene, and remarkably reduced levels of all five oxidative phosphorylation (OXPHOS) complex I-V protein subunits that are involved in the electron transport chain; these results suggested mitochondrial toxicity and abnormal OXPHOS complex protein subunits' levels in AMD cells...
October 11, 2018: Scientific Reports
Giuseppa Visalli, Nadia Ferlazzo, Alessio Facciolà, Isa Picerno, Michele Navarra, Angela Di Pietro
The physio-pathological role of mitochondria in aging and age-related diseases has stimulated the search for compounds able to promote mitochondrial functionality. Our study was designed to evaluate the effect of a white grape juice extract (WGJe) on mitochondrial activity, in an ex vivo experimental model consisting of activated lymphocytes obtained from a younger age group and an older age group of subjects. WGJe steadily decreased the lymphocytic mitochondrial mass in the older subjects, without a relevant effect in their younger counterpart, and significantly enhanced Δψm in both groups investigated...
October 11, 2018: Natural Product Research
Hyon-Seung Yi, Joon Young Chang, Minho Shong
Mitochondria perform essential roles as crucial organelles for cellular and systemic energy homeostasis, and as signaling hubs, which coordinate nuclear transcriptional responses to the intra- and extra-cellular environment. Complex human diseases, including diabetes, obesity, fatty liver disease and aging-related degenerative diseases are associated with alterations in mitochondrial oxidative phosphorylation (OxPhos) function. However, a recent series of studies in animal models have revealed that an integrated response to tolerable mitochondrial stress appears to render cells less susceptible to subsequent aging processes and metabolic stresses, which is a key feature of mitohormesis...
October 1, 2018: Journal of Molecular Endocrinology
Pedro F Almaida-Pagan, Carmen Ortega-Sabater, Alejandro Lucas-Sanchez, Daniel Gonzalez-Silvera, Antonio Martinez-Nicolas, Maria Angeles Rol de Lama, Pilar Mendiola, Jorge de Costa
Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging, especially during phases of high oxidative stress that result in molecular damage. Changes affecting lipid class or fatty acid (FA) compositions could affect phospholipid (PL) properties and alter mitochondrial function. In the present study, mitochondrial membrane PL compositions were analysed throughout the life-cycle of Nothobranchius furzeri, a species with explosive growth and one of the shortest-lived vertebrates...
October 9, 2018: Biogerontology
I C Tobias, R Khazaee, D H Betts
Dynamic alterations to mitochondrial structure and function regulate cell fate decisions and underlie multiple age-related and genetic diseases that are modeled using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Transmission electron microscopy (TEM) can be used to obtain high-resolution micrographs of mitochondria, but mitochondrial ultrastructure is easily distorted during specimen processing. This unit describes a method that preserves mitochondrial membrane structure from adherent ESC cultures for TEM sample preparation...
October 10, 2018: Current Protocols in Stem Cell Biology
Edward M Germany, Nataliya Zahayko, Mason L Huebsch, Jennifer L Fox, Veena Prahlad, Oleh Khalimonchuk
Mitochondrial functions are critical for cellular physiology; therefore, several conserved mechanisms are in place to maintain the functional integrity of mitochondria. However, many of the molecular details and components involved in ensuring mitochondrial fidelity remain obscure. Here we identify a novel role for the conserved mitochondrial AAA ATPase Afg1 in mediating mitochondrial protein homeostasis during aging and in response to various cellular challenges. Saccharomyces cerevisiae cells lacking functional Afg1 are hypersensitive to oxidative insults, unable to tolerate protein misfolding in the matrix compartment, and exhibit progressive mitochondrial failure as they age...
October 11, 2018: Journal of Cell Science
Damien Laporte, Laëtitia Gouleme, Laure Jimenez, Ines Khemiri, Isabelle Sagot
Most cells spend the majority of their life in a non-proliferating state. When proliferation cessation is irreversible, cells are senescent. By contrast, if the arrest is only temporary, cells are defined as quiescent. These cellular states are hardly distinguishable without triggering proliferation resumption, hampering thus the study of quiescent cells properties. Here we show that quiescent and senescent yeast cells are recognizable based on their mitochondrial network morphology. Indeed, while quiescent yeast cells display numerous small vesicular mitochondria, senescent cells exhibit few globular mitochondria...
October 9, 2018: ELife
James C Jiang, Stefan W Stumpferl, S Michal Jazwinski
The replicative lifespan of the yeast Saccharomyces cerevisiae models the aging of stem cells. Age asymmetry between the mother and daughter cells is established during each cell division, such that the daughter retains the capacity for self-renewal while this ability is diminished in the mother. The segregation of fully-functional mitochondria to daughter cells is one mechanism that underlies this age asymmetry. In this study, we have examined the role of mitochondrial dynamics in this phenomenon. Mitochondrial dynamics involve the processes of fission and fusion...
October 8, 2018: Biogerontology
Refilwe Lukhwareni, Cobus van Dyk
This study aimed to assess the macroscopic appearance, histology and ultrastructure of liver nodular alterations in sharptooth catfish Clarias gariepinus (Burchell, 1822) from a hyper-eutrophic freshwater impoundment. The livers of 25 fish were sampled for microscopy analyses, otoliths were collected for age estimation, and the hepatosomatic index (HSI) was calculated. The light microscopic analysis of the nodular tissue revealed hepatocellular and nuclear pleomorphism, pyknotic nuclei, variation in cytoplasmic appearance and focal areas of cellular alterations (FCAs)...
October 7, 2018: Journal of Fish Diseases
Vo Van Giau, Seong Soo A An, John P Hulme
Alzheimer's Disease (AD) is one of the most common age-related neurodegenerative diseases in the developed world. Treatment of AD is particularly challenging as the drug must overcome the blood brain barrier (BBB) before it can reach its target. Mitochondria are recognized as one of the most important targets for neurological drugs as the organelle is known to play a critical role in diverse cellular processes such as energy production and apoptosis regulation. Mitochondrial targeting was originally developed to study mitochondrial dysfunction and the organelles interaction with other sub-cellular organelles...
September 28, 2018: Journal of the Neurological Sciences
Cristina Minnelli, Paolo Moretti, Gianluca Fulgenzi, Paolo Mariani, Emiliano Laudadio, Tatiana Armeni, Roberta Galeazzi, Giovanna Mobbili
Epigallocatechin-3-gallate (EGCG) is a polyphenolic catechin from green tea, well known for being bioactive in age-associated pathologies where oxidative stress plays a preeminent role. The activity of this molecule is however contrasted by its high chemical and metabolic instability that determines a poor concentration of the antioxidant within the biological system after administration. In order to protect the molecule and increase its delivery efficiency, we have encapsulated EGCG inside anionic liposomes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and cholesteryl hemisuccinate...
October 3, 2018: International Journal of Pharmaceutics
Alexandra Moyzis, Åsa B Gustafsson
The heart is composed of cardiomyocytes that require large amounts of energy to sustain contraction. Mitochondria are distinctive organelles of bacterial origin that generate most of the energy for the heart via oxidative phosphorylation. To ensure a healthy population of mitochondria that efficiently produce ATP, myocytes quickly eliminate any unhealthy or unwanted mitochondria via a process known as mitochondrial autophagy, or mitophagy. It is especially important to selectively remove damaged or aged mitochondria since they can become excessive producers of reactive oxygen species and release pro-death proteins...
October 2, 2018: Biochimica et biophysica acta. Molecular basis of disease
Axel J Berky, Ian T Ryde, Beth Feingold, Ernesto J Ortiz, Lauren H Wyatt, Caren Weinhouse, Heileen Hsu-Kim, Joel N Meyer, William K Pan
Mitochondrial DNA (mtDNA) copy number (CN) and damage in circulating white blood cells have been proposed as effect biomarkers for pollutant exposures. Studies have shown that mercury accumulates in mitochondria and affects mitochondrial function and integrity; however, these data are derived largely from experiments in model systems, rather than human population studies that evaluate the potential utility of mitochondrial exposure biomarkers. We measured mtDNA CN and damage in white blood cells (WBCs) from 83 residents of nine communities in the Madre de Dios region of the Peruvian Amazon that vary in proximity to artisanal and small-scale gold mining...
October 5, 2018: Environmental and Molecular Mutagenesis
Cicera Edna Barbosa David, Aline Maria Brito Lucas, Maria Thalyne Silva Araújo, Beatriz Neves Coelho, Juarez Braga Soares Neto, Bruna Raysa Campos Portela, Anna Lídia Nunes Varela, Alicia J Kowaltowski, Heberty T Facundo
Oxidative stress has been implicated in the pathogenesis of cardiac hypertrophy and associated heart failure. Cardiac tissue grows in response to pressure or volume overload, leading to wall thickening or chamber enlargement. If sustained, this condition will lead to a dysfunctional cardiac tissue and oxidative stress. Calorie restriction (CR) is a powerful intervention to improve health and delay aging. Here, we investigated whether calorie restriction in mice prevented isoproterenol-induced cardiac hypertrophy in vivo by avoiding reactive oxygen species (ROS) production and maintaining antioxidant enzymatic activity...
September 5, 2018: Journal of Nutritional Biochemistry
Paula Rebelo, Marta Giacomello, Luca Scorrano
How neuromuscular junctions (NMJs) are lost in disease and aging is unclear. Recently in Cell Metabolism, Wang et al. (2018) discovered that endoplasmic reticulum-mitochondria tethering by Mitofusin 2 is required to organize a cleft between these two organelles, which, like a lorry, traffics down the axon to distribute calpastatin to terminals where it blocks NMJ degradation.
October 2, 2018: Cell Metabolism
Annelise Francisco, Juliana A Ronchi, Claudia D C Navarro, Tiago R Figueira, Roger F Castilho
Among mitochondrial NADP-reducing enzymes, nicotinamide nucleotide transhydrogenase (NNT) establishes an elevated matrix NADPH/NADP+ by catalyzing the reduction of NADP+ at the expense of NADH oxidation coupled to inward proton translocation across the inner mitochondrial membrane. Here, we characterize NNT activity and mitochondrial redox balance in the brain using a congenic mouse model carrying the mutated Nnt gene from the C57BL/6J strain. The absence of NNT activity resulted in lower total NADPH sources activity in the brain mitochondria of young mice, an effect that was partially compensated in aged mice...
October 3, 2018: Journal of Neurochemistry
Su-Zi Yoo, Mi-Hyun No, Jun-Won Heo, Dong-Ho Park, Ju-Hee Kang, So Hun Kim, Hyo-Bum Kwak
Sarcopenia is an age-associated decline of skeletal muscle mass and function and is known to lead to frailty, cachexia, osteoporosis, metabolic syndromes, and death. Notwithstanding the increasing incidence of sarcopenia, the molecular and cellular mechanisms driving age-related sarcopenia are not completely understood. This article reviews current definitions of sarcopenia, its potential mechanisms, and effects of exercise on sarcopenia. The pathogenesis of age-related sarcopenia is multifactorial and includes myostatin, inflammatory cytokines, and mitochondria-derived problems...
August 2018: Journal of Exercise Rehabilitation
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