scholarly journals Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility

Aging Cell ◽  
2021 ◽  
Author(s):  
Jingwen Zhang ◽  
Zhibin He ◽  
Julia Fedorova ◽  
Cole Logan ◽  
Lauryn Bates ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Age Related ◽  
Cardiomyocyte Contractility

scholarly journals Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Miwa Nahata ◽  
Sachiko Mogami ◽  
Hitomi Sekine ◽  
Seiichi Iizuka ◽  
Naoto Okubo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Energy Homeostasis ◽  
Mitochondrial Dynamics ◽  
Negative Regulator ◽  
Aged Mice ◽  
Glucose Levels ◽  
Therapeutic Benefits ◽  
Age Related ◽  
Daily Food ◽  
Young Mice

AbstractChronic undernutrition contributes to the increase in frailty observed among elderly adults, which is a pressing issue in the sector of health care for older people worldwide. Autophagy, an intracellular recycling system, is closely associated with age-related pathologies. Therefore, decreased autophagy in aging could be involved in the disruption of energy homeostasis that occurs during undernutrition; however, the physiological mechanisms underlying this process remain unknown. Here, we showed that 70% daily food restriction (FR) induced fatal hypoglycemia in 23–26-month-old (aged) mice, which exhibited significantly lower hepatic autophagy than 9-week-old (young) mice. The liver expressions of Bcl-2, an autophagy-negative regulator, and Beclin1–Bcl-2 binding, were increased in aged mice compared with young mice. The autophagy inducer Tat-Beclin1 D11, not the mTOR inhibitor rapamycin, decreased the plasma levels of the glucogenic amino acid and restored the blood glucose levels in aged FR mice. Decreased liver gluconeogenesis, body temperature, physical activity, amino acid metabolism, and hepatic mitochondrial dynamics were observed in the aged FR mice. These changes were restored by treatment with hochuekkito that is a herbal formula containing several autophagy-activating ingredients. Our results indicate that Bcl-2 upregulation in the liver during the aging process disturbs autophagy activation, which increases the vulnerability to undernutrition. The promotion of liver autophagy may offer clinical therapeutic benefits to frail elderly patients.

scholarly journals Integrating multiple aspects of mitochondrial dynamics in neurons: Age-related differences and dynamic changes in a chronic rotenone model

2011 ◽  
Vol 41 (1) ◽  
pp. 189-200 ◽  
Author(s):  
Beth Arnold ◽  
Steven J. Cassady ◽  
Victor S. VanLaar ◽  
Sarah B. Berman
Keyword(s):  
Mitochondrial Dynamics ◽  
Dynamic Changes ◽  
Age Related

scholarly journals Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 598 ◽  
Author(s):  
Anna Picca ◽  
Riccardo Calvani ◽  
Hélio José Coelho-Junior ◽  
Francesco Landi ◽  
Roberto Bernabei ◽  
...  
Keyword(s):  
Quality Control ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Age Related ◽  
Bidirectional Communication ◽  
Membrane Contact ◽  
Organelle Membrane

Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson’s disease as a prototypical geroscience condition.

scholarly journals Moderation of mitochondrial respiration mitigates metabolic syndrome of aging

2020 ◽  
Vol 117 (18) ◽  
pp. 9840-9850 ◽  
Author(s):  
Mojdeh Tavallaie ◽  
Ramouna Voshtani ◽  
Xinxian Deng ◽  
Yixue Qiao ◽  
Faqin Jiang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mitochondrial Respiration ◽  
Mitochondrial Dynamics ◽  
Atp Synthesis ◽  
Control Group ◽  
Standard Diet ◽  
Ros Production ◽  
Metabolic Complications ◽  
Age Related ◽  
Mitochondrial Functions

Deregulation of mitochondrial dynamics leads to the accumulation of oxidative stress and unhealthy mitochondria; consequently, this accumulation contributes to premature aging and alterations in mitochondria linked to metabolic complications. We postulate that restrained mitochondrial ATP synthesis might alleviate age-associated disorders and extend healthspan in mammals. Herein, we prepared a previously discovered mitochondrial complex IV moderate inhibitor in drinking water and orally administered to standard-diet-fed, wild-type C57BL/6J mice every day for up to 16 mo. No manifestation of any apparent toxicity or deleterious effect on studied mouse models was observed. The impacts of an added inhibitor on a variety of mitochondrial functions were analyzed, such as respiratory activity, mitochondrial bioenergetics, and biogenesis, and a few age-associated comorbidities, including reactive oxygen species (ROS) production, glucose abnormalities, and obesity in mice. It was found that mitochondrial quality, dynamics, and oxidative metabolism were greatly improved, resulting in lean mice with a specific reduction in visceral fat plus superb energy and glucose homeostasis during their aging period compared to the control group. These results strongly suggest that a mild interference in ATP synthesis through moderation of mitochondrial activity could effectively up-regulate mitogenesis, reduce ROS production, and preserve mitochondrial integrity, thereby impeding the onset of metabolic syndrome. We conclude that this inhibitory intervention in mitochondrial respiration rectified the age-related physiological breakdown in mice by protecting mitochondrial function and markedly mitigated certain undesired primary outcomes of metabolic syndrome, such as obesity and type 2 diabetes. This intervention warrants further research on the treatment of metabolic syndrome of aging in humans.

scholarly journals Targeting Mitochondrial Network Architecture in Down Syndrome and Aging

2020 ◽  
Vol 21 (9) ◽  
pp. 3134 ◽  
Author(s):  
Nunzia Mollo ◽  
Rita Cicatiello ◽  
Miriam Aurilia ◽  
Roberta Scognamiglio ◽  
Rita Genesio ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Network Architecture ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mammalian Target Of Rapamycin ◽  
Protective Effects ◽  
Mitochondrial Network ◽  
Factors Affecting ◽  
Age Related ◽  
Underlying Causes

Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appears to depend upon their network architecture that may dynamically pass from an interconnected structure with long tubular units, to a fragmented one with short separate fragments. A decline in mitochondrial quality, which presents itself as an altered structural organization and a function of mitochondria, has been observed in Down syndrome (DS), as well as in aging and in age-related pathologies. This review provides a basic overview of mitochondrial dynamics, from fission/fusion mechanisms to mitochondrial homeostasis. Molecular mechanisms determining the disruption of the mitochondrial phenotype in DS and aging are discussed. The impaired activity of the transcriptional co-activator PGC-1α/PPARGC1A and the hyperactivation of the mammalian target of rapamycin (mTOR) kinase are emerging as molecular underlying causes of these mitochondrial alterations. It is, therefore, likely that either stimulating the PGC-1α activity or inhibiting mTOR signaling could reverse mitochondrial dysfunction. Evidence is summarized suggesting that drugs targeting either these pathways or other factors affecting the mitochondrial network may represent therapeutic approaches to improve and/or prevent the effects of altered mitochondrial function. Overall, from all these studies it emerges that the implementation of such strategies may exert protective effects in DS and age-related diseases.

scholarly journals Mitochondrial Aging and Age-Related Dysfunction of Mitochondria

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dimitry A. Chistiakov ◽  
Igor A. Sobenin ◽  
Victor V. Revin ◽  
Alexander N. Orekhov ◽  
Yuri V. Bobryshev
Keyword(s):  
Mitochondrial Function ◽  
Antioxidant Defense ◽  
Mitochondrial Dynamics ◽  
Oxidative Capacity ◽  
Ros Generation ◽  
Atp Production ◽  
Age Related ◽  
Related Phenotype ◽  
Age Dependent ◽  
Aged Subjects

Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense. Mitochondrial biogenesis declines with age due to alterations in mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria. Age-dependent abnormalities in mitochondrial quality control further weaken and impair mitochondrial function. In aged tissues, enhanced mitochondria-mediated apoptosis contributes to an increase in the percentage of apoptotic cells. However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging and attenuate the age-related phenotype in humans.

scholarly journals Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Steffen Häseli ◽  
Stefanie Deubel ◽  
Tobias Jung ◽  
Tilman Grune ◽  
Christiane Ott
Keyword(s):  
Molecular Mechanisms ◽  
Functional Model ◽  
Model System ◽  
Premature Senescence ◽  
Cell Cycle Regulators ◽  
Neonatal Cardiomyocytes ◽  
Age Related ◽  
Cardiomyocyte Contractility ◽  
Postnatal Environment ◽  
Age Related Changes

Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated β-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.

scholarly journals Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

2013 ◽  
Vol 305 (4) ◽  
pp. H459-H476 ◽  
Author(s):  
Emanuele Marzetti ◽  
Anna Csiszar ◽  
Debapriya Dutta ◽  
Gauthami Balagopal ◽  
Riccardo Calvani ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cardiovascular System ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Late Life ◽  
Age Related ◽  
Functional Consequences ◽  
Cardiovascular Aging ◽  
The Life Course

Advanced age is associated with a disproportionate prevalence of cardiovascular disease (CVD). Intrinsic alterations in the heart and the vasculature occurring over the life course render the cardiovascular system more vulnerable to various stressors in late life, ultimately favoring the development of CVD. Several lines of evidence indicate mitochondrial dysfunction as a major contributor to cardiovascular senescence. Besides being less bioenergetically efficient, damaged mitochondria also produce increased amounts of reactive oxygen species, with detrimental structural and functional consequences for the cardiovascular system. The age-related accumulation of dysfunctional mitochondrial likely results from the combination of impaired clearance of damaged organelles by autophagy and inadequate replenishment of the cellular mitochondrial pool by mitochondriogenesis. In this review, we summarize the current knowledge about relevant mechanisms and consequences of age-related mitochondrial decay and alterations in mitochondrial quality control in the cardiovascular system. The involvement of mitochondrial dysfunction in the pathogenesis of cardiovascular conditions especially prevalent in late life and the emerging connections with neurodegeneration are also illustrated. Special emphasis is placed on recent discoveries on the role played by alterations in mitochondrial dynamics (fusion and fission), mitophagy, and their interconnections in the context of age-related CVD and endothelial dysfunction. Finally, we discuss pharmacological interventions targeting mitochondrial dysfunction to delay cardiovascular aging and manage CVD.

scholarly journals Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans

2018 ◽  
Author(s):  
Chia-An Yen ◽  
Dana L. Ruter ◽  
Christian D. Turner ◽  
Shanshan Pang ◽  
Sean P. Curran
Keyword(s):  
Flavin Adenine Dinucleotide ◽  
Sperm Quality ◽  
Mitochondrial Dynamics ◽  
Sperm Function ◽  
Loss Of Function ◽  
C Elegans ◽  
Age Related ◽  
Proline Catabolism ◽  
A Cell ◽  
The Impact

ABSTRACTExposure to environmental stress is clinically established to influence male reproductive health, but the impact of normal cellular metabolism on sperm quality is less well-defined. Here we show that impaired mitochondrial proline catabolism, reduces energy-storing flavin adenine dinucleotide (FAD) levels, alters mitochondrial dynamics toward fusion, and leads to age-related loss of sperm quality (size and activity), which reduces competitive fitness. Loss of the 1-pyrroline-5-carboxylate dehydrogenase enzyme alh-6 that catalyzes the second step in mitochondrial proline catabolism, leads to premature male reproductive senescence. Reducing the expression of the proline catabolism enzyme alh-6 or FAD biosynthesis pathway genes in the germline is sufficient to recapitulate the sperm-related phenotypes observed in alh-6 loss-of-function mutants. These sperm-specific defects are suppressed by feeding diets that restore FAD levels. Our results define a cell autonomous role for mitochondrial proline catabolism and FAD homeostasis on sperm function and specify strategies to pharmacologically reverse these defects.

Sign in / Sign up

Export Citation Format

Share Document