scholarly journals Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes

2020 ◽  
Author(s):  
Matthieu Mantecon ◽  
Laura Le Pelletier ◽  
Jennifer Gorwood ◽  
Martine Auclair ◽  
Michael Atlan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Subcutaneous Fat ◽  
Normal Weight ◽  
Young Donor ◽  
Age Related ◽  
Fat Redistribution ◽  
Amp Activated Protein Kinase ◽  
Aged Donor

SUMMARYAging is associated with central fat redistribution, and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived-stemcells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25y) or older women (>60y).Aged-donor ASCs showed more intense features of aging (senescence, mitochondrial dysfunction, and oxidative stress) than young-donor ASCs. Oxidative stress and mitochondrial dysfunction occurred earlier in adipocytes derived from aged-donor than from young-donor ASCs, leading to insulin resistance and impaired adipogenesis.When aged-donor ASCs were treated with metformin, senescence, oxidative stress and mitochondrial dysfunction returned to the levels observed in young-donor ASCs. Furthermore, metformin’s prevention of senescence and dysfunction during ASC proliferation restored the cells’ adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated-protein-kinase.We show here that targeting senescent ASCs from aged women with metformin may alleviate age-related dysfunction, insulin resistance, and impaired adipogenesis.

scholarly journals Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Laura Le Pelletier ◽  
Matthieu Mantecon ◽  
Jennifer Gorwood ◽  
Martine Auclair ◽  
Roberta Foresti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Sensitivity ◽  
Mitochondrial Dysfunction ◽  
Stromal Cells ◽  
Subcutaneous Fat ◽  
Normal Weight ◽  
Young Donor ◽  
Age Related ◽  
Aged Donor

Aging is associated with central fat redistribution and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived-stromal cells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25y) or older women (>60y). Increased cell passages of young-donor ASCs (in vitro aging), resulted in senescence but not oxidative stress. ASC-derived adipocytes presented impaired adipogenesis but no early mitochondrial dysfunction. Conversely, aged-donor ASCs at early passages displayed oxidative stress and mild senescence. ASC-derived adipocytes exhibited oxidative stress, and early mitochondrial dysfunction but adipogenesis was preserved. In vitro aging of aged-donor ASCs resulted in further increased senescence, mitochondrial dysfunction, oxidative stress and severe adipocyte dysfunction. When in vitro aged young-donor ASCs were treated with metformin, no alteration was alleviated. Conversely, metformin treatment of aged-donor ASCs decreased oxidative stress and mitochondrial dysfunction resulting in decreased senescence. Metformin's prevention of oxidative stress and of the resulting senescence improved the cells' adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated-protein-kinase as revealed by its specific inhibition and activation. Overall, aging ASC-derived adipocytes presented impaired adipogenesis and insulin sensitivity. Targeting stress-induced senescence of ASCs with metformin may improve age-related adipose tissue dysfunction.

scholarly journals Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

2019 ◽  
Vol 8 (9) ◽  
pp. 1385 ◽  
Author(s):  
Burgos-Morón ◽  
Abad-Jiménez ◽  
Marañón ◽  
Iannantuoni ◽  
Escribano-López ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Β Cells ◽  
The Relationship ◽  
And Oxidative Stress

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

scholarly journals Honeybush Extracts (Cyclopia spp.) Rescue Mitochondrial Functions and Bioenergetics against Oxidative Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Anastasia Agapouda ◽  
Veronika Butterweck ◽  
Matthias Hamburger ◽  
Dalene de Beer ◽  
Elizabeth Joubert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Hot Water ◽  
Human Neuroblastoma ◽  
Atp Production ◽  
Physiological Conditions ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Scientific Attention

Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Cyclopia species are endemic South African plants and some have a long tradition of use as herbal tea, known as honeybush tea. Extracts of the tea are gaining more scientific attention due to their phenolic composition. In the present study, we tested not only the in vitro mitochondria-enhancing properties of honeybush extracts under physiological conditions but also their ameliorative properties under oxidative stress situations. Hot water and ethanolic extracts of C. subternata, C. genistoides, and C. longifolia were investigated. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts, at a concentration range of 0.1-1 ng/ml, had a beneficial effect on bioenergetics as it increased ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides, in particular, showed a protective effect by rescuing the bioenergetic and mitochondrial deficits under oxidative stress conditions (400 μM H2O2 for 3 hours). These findings indicate that honeybush extracts could constitute candidates for the prevention of oxidative stress with an impact on aging processes and age-related neurodegenerative disorders potentially leading to the development of a condition-specific nutraceutical.

scholarly journals Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 109 ◽  
Author(s):  
Chisato Fujimoto ◽  
Tatsuya Yamasoba
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Mitochondrial Dysfunction ◽  
Cell Lines ◽  
Mitochondrial Gene ◽  
Protective Effects ◽  
Drug Induced ◽  
Age Related ◽  
Cochlear Damage ◽  
Age Related Hearing Loss

Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

scholarly journals Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Giuseppe Verdile ◽  
Kevin N. Keane ◽  
Vinicius F. Cruzat ◽  
Sandra Medic ◽  
Miheer Sabale ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Insulin Signalling ◽  
Contributory Factor ◽  
Protein Accumulation ◽  
Age Related ◽  
Impaired Insulin ◽  
And Oxidative Stress

Type 2 diabetes (T2DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β(Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.

scholarly journals Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution

2006 ◽  
Vol 100 (2) ◽  
pp. 609-614 ◽  
Author(s):  
Martin Torriani ◽  
Bijoy J. Thomas ◽  
Robert B. Barlow ◽  
Jamie Librizzi ◽  
Sara Dolan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Magnetic Resonance ◽  
Subcutaneous Fat ◽  
Abdominal Fat ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Intramyocellular Lipid ◽  
Fat Redistribution ◽  
Visceral Abdominal Fat

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution ( n = 25), and age- and body mass index-matched HIV-negative controls ( n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 ± 11.5 vs. 85.1 ± 13.2 institutional units (IU); P = 0.007] and soleus [643.7 ± 61.0 vs. 443.6 ± 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 ± 2.3 vs. 35.0 ± 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 ± 1.1 vs. 15.6 ± 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 ± 11.3 vs. 74.4 ± 12.3 cm2, P = 0.004), triglycerides (131.1 ± 11.0 vs. 66.3 ± 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 ± 0.9 vs. 7.0 ± 0.9 μIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides ( r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA ( r = −0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (β = −633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.

scholarly journals Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats

2019 ◽  
Vol 241 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Jirapas Sripetchwandee ◽  
Hiranya Pintana ◽  
Piangkwan Sa-nguanmoo ◽  
Chiraphat Boonnag ◽  
Wasana Pratchayasakul ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cognitive Decline ◽  
Mitochondrial Dysfunction ◽  
Dendritic Spine ◽  
High Fat Diet ◽  
High Fat ◽  
Long Term Depression ◽  
Impaired Insulin

Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone deprivation on the brain are still lacking. Adult Wistar rats from both genders were operated upon (sham operations or orchiectomies/ovariectomies) and given a normal diet or high-fat diet for 4, 8 and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density and cognitive decline by week 12. In normal diet-fed rats, estrogen deprivation, not testosterone deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity and reduced dendritic spine density. In high-fat–diet-fed rats, estrogen deprivation, not testosterone deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.

scholarly journals Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

2020 ◽  
Author(s):  
MYUNG HEE KIM ◽  
Dae Hyun Kim ◽  
Su Geun Yang ◽  
Dae Yu Kim
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Transcription Factors ◽  
Mitochondrial Dysfunction ◽  
Retinal Pigment ◽  
Protective Role ◽  
Age Related Macular Degeneration ◽  
Ros Generation ◽  
Rpe Cells ◽  
Age Related

Abstract Background: Oxidative damage in retinal pigmented epithelium (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of TPP-Niacin against the hydrogen peroxide (H2O2)-induced oxidative stress to RPE cells. Methods: The cellular viability, lactate dehydrogenase, reactive oxygen species (ROS), and mitochondrial function were determined in the retinal ARPE-19 cells under the treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-PCR). Results: TPP-Niacin significantly improved cell viability reduction, reduced ROS generation and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from H2O2-induced oxidative stress was also significantly diminished by the TPP-Niacin treatment, reduced generation of ROS, an ameliorated reduction of mitochondrial membrane potential (MMP) and an upregulated mitochondrial associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant associated genes (especially, HO-1 and NQO-1). Conclusion: We proved the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to have played a protective role against mitochondrial dysfunction by up-regulating antioxidant-related genes such as PGC-1α, NRF2, HO-1 and NQO-1 in RPE cells.

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