Reversible Inhibition of Mitochondrial Function by Oxidative Stress Contributes to Age-Related Mitochondrial Deficits

2012 ◽  
Vol 53 ◽  
pp. S125
Author(s):  
David J. Marcinek ◽  
Shane E. Kruse ◽  
Michael P. Siegel ◽  
Hazel H. Szeto
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Reversible Inhibition ◽  
Age Related

scholarly journals Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function

2019 ◽  
Vol 57 (3) ◽  
pp. 1317-1331 ◽  
Author(s):  
Gavin Pharaoh ◽  
Daniel Owen ◽  
Alexander Yeganeh ◽  
Pavithra Premkumar ◽  
Julie Farley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Function ◽  
Spatial Learning ◽  
Mitochondrial Function ◽  
Coupling Efficiency ◽  
Redox Status ◽  
Cellular Aging ◽  
Age Related ◽  
The Brain ◽  
Circulating Levels

AbstractAge-related decline in circulating levels of insulin-like growth factor (IGF)-1 is associated with reduced cognitive function, neuronal aging, and neurodegeneration. Decreased mitochondrial function along with increased reactive oxygen species (ROS) and accumulation of damaged macromolecules are hallmarks of cellular aging. Based on numerous studies indicating pleiotropic effects of IGF-1 during aging, we compared the central and peripheral effects of circulating IGF-1 deficiency on tissue mitochondrial function using an inducible liver IGF-1 knockout (LID). Circulating levels of IGF-1 (~ 75%) were depleted in adult male Igf1f/f mice via AAV-mediated knockdown of hepatic IGF-1 at 5 months of age. Cognitive function was evaluated at 18 months using the radial arm water maze and glucose and insulin tolerance assessed. Mitochondrial function was analyzed in hippocampus, muscle, and visceral fat tissues using high-resolution respirometry O2K as well as redox status and oxidative stress in the cortex. Peripherally, IGF-1 deficiency did not significantly impact muscle mass or mitochondrial function. Aged LID mice were insulin resistant and exhibited ~ 60% less adipose tissue but increased fat mitochondrial respiration (20%). The effects on fat metabolism were attributed to increases in growth hormone. Centrally, IGF-1 deficiency impaired hippocampal-dependent spatial acquisition as well as reversal learning in male mice. Hippocampal mitochondrial OXPHOS coupling efficiency and cortex ATP levels (~ 50%) were decreased and hippocampal oxidative stress (protein carbonylation and F2-isoprostanes) was increased. These data suggest that IGF-1 is critical for regulating mitochondrial function, redox status, and spatial learning in the central nervous system but has limited impact on peripheral (liver and muscle) metabolism with age. Therefore, IGF-1 deficiency with age may increase sensitivity to damage in the brain and propensity for cognitive deficits. Targeting mitochondrial function in the brain may be an avenue for therapy of age-related impairment of cognitive function. Regulation of mitochondrial function and redox status by IGF-1 is essential to maintain brain function and coordinate hippocampal-dependent spatial learning. While a decline in IGF-1 in the periphery may be beneficial to avert cancer progression, diminished central IGF-1 signaling may mediate, in part, age-related cognitive dysfunction and cognitive pathologies potentially by decreasing mitochondrial function.

scholarly journals Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hirotaka Yamamoto ◽  
Katsutaro Morino ◽  
Lemecha Mengistu ◽  
Taishi Ishibashi ◽  
Kohei Kiriyama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Cell ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Skeletal Muscle Cell ◽  
Antioxidant Systems ◽  
Respiratory Capacity ◽  
Age Related ◽  
Murine Skeletal Muscle

Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS) levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders.

Mitochondrial decline and chronic conditions of older adults

2017 ◽  
pp. 337-344
Author(s):  
Emanuele Marzetti ◽  
Francesco Landi ◽  
Francesca Martini ◽  
Christiaan Leeuwenburgh ◽  
Riccardo Calvani
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Functional Decline ◽  
Causative Factor ◽  
Common Denominator ◽  
Cellular Viability ◽  
Major Mechanism ◽  
Mtdna Mutations ◽  
Age Related

Ageing involves a progressive deterioration of physiological integrity which leads to increased vulnerability to stressors and multisystemic functional decline. Mitochondrial dysfunction is increasingly recognized as a common denominator of ageing and an important causative factor for major age-related conditions. Mitochondrial function becomes perturbed by age-associated accumulation of mtDNA mutations, altered mitochondriogenesis and dynamics, and abnormal regulation of mitophagy. These alterations result in diminished bioenergetic efficacy, enhanced oxidative stress, and eventually loss of cellular viability. This series of events is proposed to be a major mechanism in the ageing process and the development of chronic diseases. This chapter provides an overview on the mechanisms believed to underlie the loss of mitochondrial function with ageing. Special attention is paid to the consequences of mitochondrial dysfunction in postmitotic tissues (i.e. heart, skeletal muscle, and central nervous system), where mitochondrial damage is proposed to be responsible for the appearance of age- and disease-associated phenotypes.

scholarly journals Decreased in vitro Mitochondrial Function is Associated with Enhanced Brain Metabolism, Blood Flow, and Memory in Surfl-Deficient Mice

2013 ◽  
Vol 33 (10) ◽  
pp. 1605-1611 ◽  
Author(s):  
Ai-Ling Lin ◽  
Daniel A Pulliam ◽  
Sathyaseelan S Deepa ◽  
Jonathan J Halloran ◽  
Stacy A Hussong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Mitochondrial Function ◽  
Cognitive Aging ◽  
Brain Function ◽  
Brain Metabolism ◽  
Functional Changes ◽  
Positive Effects ◽  
Age Related

Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders.

scholarly journals Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Dan-Dan Zhou ◽  
Min Luo ◽  
Si-Yu Huang ◽  
Adila Saimaiti ◽  
Ao Shang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factor ◽  
Chronic Diseases ◽  
Inflammatory Reaction ◽  
Mitochondrial Function ◽  
Red Wine ◽  
Life Extension ◽  
Age Related ◽  
Stress Relieving ◽  
Prevention And Treatment

The aging of population has become an issue of great concern because of its rapid increase. Aging is an important risk factor of many chronic diseases. Resveratrol could be found in many foods, such as grapes, red wine, peanuts, and blueberries. Many studies reported that resveratrol possessed various bioactivities, such as antioxidant, anti-inflammatory, cardiovascular protection, anticancer, antidiabetes mellitus, antiobesity, neuroprotection, and antiaging effects. The antiaging mechanisms of resveratrol were mainly ameliorating oxidative stress, relieving inflammatory reaction, improving mitochondrial function, and regulating apoptosis. Resveratrol could be an effective and safe compound for the prevention and treatment of aging and age-related diseases. In this review, we summarize the effects of resveratrol on aging, life extension, and several age-related diseases, with special attention paid to the mechanisms of antiaging action.

Age-Related Changes in Activation of Mitogen-Activated Protein Kinase Cascades by Oxidative Stress

1998 ◽  
Vol 3 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Kathryn Z Guyton ◽  
Myriani Gorospe ◽  
Xiantao Wang ◽  
Yolanda D Mock ◽  
Gertrude C Kokkonen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Age Related ◽  
Mitogen Activated Protein ◽  
Age Related Changes

Oxidative Stress, Ocular Disease and Diabetes Retinopathy

2019 ◽  
Vol 24 (40) ◽  
pp. 4726-4741 ◽  
Author(s):  
Orathai Tangvarasittichai ◽  
Surapon Tangvarasittichai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Protein Modification ◽  
Morphological Changes ◽  
Corneal Dystrophy ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Retinal Light Damage ◽  
Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

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