scholarly journals Caloric Restriction and the Nutrient-Sensing PGC-1αin Mitochondrial Homeostasis: New Perspectives in Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Daniele Lettieri Barbato ◽  
Sara Baldelli ◽  
Beatrice Pagliei ◽  
Katia Aquilano ◽  
Maria Rosa Ciriolo
Keyword(s):  
Neurodegenerative Diseases ◽  
Caloric Restriction ◽  
Mitochondrial Biogenesis ◽  
Dietary Intervention ◽  
Current Knowledge ◽  
Nutritional Intervention ◽  
Nutrient Sensing ◽  
Mitochondrial Activity ◽  
Beneficial Effects ◽  
And Function

Mitochondrial activity progressively declines during ageing and in many neurodegenerative diseases. Caloric restriction (CR) has been suggested as a dietary intervention that is able to postpone the detrimental aspects of aging as it ameliorates mitochondrial performance. This effect is partially due to increased mitochondrial biogenesis. The nutrient-sensing PGC-1αis a transcriptional coactivator that promotes the expression of mitochondrial genes and is induced by CR. It is believed that many of the mitochondrial and metabolic benefits of CR are due to increased PGC-1αactivity. The increase of PGC-1αis also positively linked to neuroprotection and its decrement has been involved in the pathogenesis of many neurodegenerative diseases. This paper aims to summarize the current knowledge about the role of PGC-1αin neuronal homeostasis and the beneficial effects of CR on mitochondrial biogenesis and function. We also discuss how PGC-1α-governed pathways could be used as target for nutritional intervention to prevent neurodegeneration.

scholarly journals SIRT1 Activation by Resveratrol Alleviates Cardiac Dysfunction via Mitochondrial Regulation in Diabetic Cardiomyopathy Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Sai Ma ◽  
Jing Feng ◽  
Ran Zhang ◽  
Jiangwei Chen ◽  
Dong Han ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Beneficial Effects ◽  
Mitochondrial Regulation ◽  
And Function

Background. Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. Methods and Results. Cardiac-specific SIRT1 knockout (SIRT1KO) mice were generated using Cre-loxP system. SIRT1KO mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism. DCM and SIRT1KO hearts showed impaired mitochondrial biogenesis and function, while SIRT1 activation by resveratrol reversed this in DCM mice. High glucose caused increased apoptosis, impaired mitochondrial biogenesis, and function in cardiomyocytes, which was alleviated by resveratrol. SIRT1 deletion by both SIRT1KO and shRNA abolished the beneficial effects of resveratrol. Furthermore, the function of SIRT1 is mediated via the deacetylation effect on peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), thus inducing increased expression of nuclear respiratory factor 1 (NRF-1), NRF-2, estrogen-related receptor-α (ERR-α), and mitochondrial transcription factor A (TFAM). Conclusions. Cardiac deletion of SIRT1 caused phenotypes resembling DCM. Activation of SIRT1 by resveratrol ameliorated cardiac injuries in DCM through PGC-1α-mediated mitochondrial regulation. Collectively, SIRT1 may serve as a potential therapeutic target for DCM.

scholarly journals ER-mitochondria contact sites in neurodegeneration: genetic screening approaches to investigate novel disease mechanisms

2020 ◽  
Author(s):  
Emma Louise Wilson ◽  
Emmanouil Metzakopian
Keyword(s):  
Neurodegenerative Diseases ◽  
High Throughput Screening ◽  
Current Knowledge ◽  
Unfolded Protein ◽  
Advantages And Disadvantages ◽  
Contact Sites ◽  
The Unfolded Protein Response ◽  
And Function ◽  
Protein Response ◽  
Related Proteins

AbstractMitochondria-ER contact sites (MERCS) are known to underpin many important cellular homoeostatic functions, including mitochondrial quality control, lipid metabolism, calcium homoeostasis, the unfolded protein response and ER stress. These functions are known to be dysregulated in neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD) and amyloid lateral sclerosis (ALS), and the number of disease-related proteins and genes being associated with MERCS is increasing. However, many details regarding MERCS and their role in neurodegenerative diseases remain unknown. In this review, we aim to summarise the current knowledge regarding the structure and function of MERCS, and to update the field on current research in PD, AD and ALS. Furthermore, we will evaluate high-throughput screening techniques, including RNAi vs CRISPR/Cas9, pooled vs arrayed formats and how these could be combined with current techniques to visualise MERCS. We will consider the advantages and disadvantages of each technique and how it can be utilised to uncover novel protein pathways involved in MERCS dysfunction in neurodegenerative diseases.

The effects of aging, injury and disease on microglial function: a case for cellular senescence

2007 ◽  
Vol 3 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Kelly R. Miller ◽  
Wolfgang J. Streit
Keyword(s):  
Neurodegenerative Diseases ◽  
Cellular Senescence ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Aging Brain ◽  
Normal Brain ◽  
Age Related ◽  
Anti Inflammatory ◽  
Effects Of Aging ◽  
And Function

AbstractNeuroinflammation resulting from chronic reactive microgliosis is thought to contribute to age-related neurodegeneration, as well as age-related neurodegenerative diseases, specifically Alzheimer's disease (AD). Support of this theory comes from studies reporting a progressive, age-associated increase in microglia with an activated phenotype. Although the underlying cause(s) of this microglial reactivity is idiopathic, an accepted therapeutic strategy for the treatment of AD is inhibition of microglial activation using anti-inflammatory agents. Although the effectiveness of anti-inflammatory treatment for AD remains equivocal, microglial inhibition is being tested as a potential treatment for additional neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Given the important and necessary functions of microglia in normal brain, careful evaluation of microglial function in the aged brain is a necessary first step in targeting more precise treatment strategies for aging-related neurodegenerative diseases. Studies from our laboratory have shown multiple age-related changes in microglial morphology and function that are suggestive of cellular senescence. In this manuscript, we review current knowledge of microglia in the aging brain and present new, unpublished work that further supports the theory that microglia experience an age-related decline in proliferative function as a result of cellular senescence.

scholarly journals Macronutrients and caloric intake in health and longevity

2015 ◽  
Vol 226 (1) ◽  
pp. R17-R28 ◽  
Author(s):  
Samantha M Solon-Biet ◽  
Sarah J Mitchell ◽  
Rafael de Cabo ◽  
David Raubenheimer ◽  
David G Le Couteur ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Dietary Intervention ◽  
Critical Role ◽  
Caloric Intake ◽  
Nutrient Sensing ◽  
Current Understanding ◽  
Nutritional Interventions ◽  
Wide Range ◽  
The Impact ◽  
The Relationship

Both lifespan and healthspan are influenced by nutrition, with nutritional interventions proving to be robust across a wide range of species. However, the relationship between nutrition, health and aging is still not fully understood. Caloric restriction is the most studied dietary intervention known to extend life in many organisms, but recently the balance of macronutrients has been shown to play a critical role. In this review, we discuss the current understanding regarding the impact of calories and macronutrient balance in mammalian health and longevity, and highlight the key nutrient-sensing pathways that mediate the effects of nutrition on health and ageing.

scholarly journals Oxidative-Signaling in Neural Stem Cell-Mediated Plasticity: Implications for Neurodegenerative Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1088
Author(s):  
Mafalda Ferreira dos Santos ◽  
Catarina Roxo ◽  
Susana Solá
Keyword(s):  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Bioactive Molecules ◽  
Mammalian Brain ◽  
Beneficial Effects ◽  
Mature Brain ◽  
Injured Brain ◽  
Therapeutic Properties ◽  
Adult Mammalian Brain

The adult mammalian brain is capable of generating new neurons from existing neural stem cells (NSCs) in a process called adult neurogenesis. This process, which is critical for sustaining cognition and mental health in the mature brain, can be severely hampered with ageing and different neurological disorders. Recently, it is believed that the beneficial effects of NSCs in the injured brain relies not only on their potential to differentiate and integrate into the preexisting network, but also on their secreted molecules. In fact, further insight into adult NSC function is being gained, pointing to these cells as powerful endogenous “factories” that produce and secrete a large range of bioactive molecules with therapeutic properties. Beyond anti-inflammatory, neurogenic and neurotrophic effects, NSC-derived secretome has antioxidant proprieties that prevent mitochondrial dysfunction and rescue recipient cells from oxidative damage. This is particularly important in neurodegenerative contexts, where oxidative stress and mitochondrial dysfunction play a significant role. In this review, we discuss the current knowledge and the therapeutic opportunities of NSC secretome for neurodegenerative diseases with a particular focus on mitochondria and its oxidative state.

scholarly journals Dietary restriction with and without caloric restriction for healthy aging

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 117 ◽  
Author(s):  
Changhan Lee ◽  
Valter Longo
Keyword(s):  
Adverse Effects ◽  
Caloric Restriction ◽  
Food Consumption ◽  
Dietary Restriction ◽  
Healthy Aging ◽  
Dietary Intervention ◽  
Model Organisms ◽  
Beneficial Effects ◽  
Dietary Restrictions ◽  
Safe Intervention

Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction.

scholarly journals Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaione Auzmendi-Iriarte ◽  
Ander Matheu
Keyword(s):  
Neurodegenerative Diseases ◽  
Brain Aging ◽  
Current Knowledge ◽  
Tissue Integrity ◽  
Cargo Protein ◽  
Cellular Energetics ◽  
The Individual ◽  
And Function ◽  
The Impact ◽  
Chaperone Mediated Autophagy

Brain aging is characterized by a time-dependent decline of tissue integrity and function, and it is a major risk for neurodegenerative diseases and brain cancer. Chaperone-mediated autophagy (CMA) is a selective form of autophagy specialized in protein degradation, which is based on the individual translocation of a cargo protein through the lysosomal membrane. Regulation of processes such as proteostasis, cellular energetics, or immune system activity has been associated with CMA, indicating its pivotal role in tissue homeostasis. Since first studies associating Parkinson’s disease (PD) to CMA dysfunction, increasing evidence points out that CMA is altered in both physiological and pathological brain aging. In this review article, we summarize the current knowledge regarding the impact of CMA during aging in brain physiopathology, highlighting the role of CMA in neurodegenerative diseases and glioblastoma, the most common and aggressive brain tumor in adults.

scholarly journals Mitochondrial dysfunction and consequences in calpain-3-deficient muscle

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vanessa E. Jahnke ◽  
Jennifer M. Peterson ◽  
Jack H. Van Der Meulen ◽  
Jessica Boehler ◽  
Kitipong Uaesoontrachoon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Mitochondrial Activity ◽  
Calpain 3 ◽  
And Function ◽  
Deficient Mice

Abstract Background Nonsense or loss-of-function mutations in the non-lysosomal cysteine protease calpain-3 result in limb-girdle muscular dystrophy type 2A (LGMD2A). While calpain-3 is implicated in muscle cell differentiation, sarcomere formation, and muscle cytoskeletal remodeling, the physiological basis for LGMD2A has remained elusive. Methods Cell growth, gene expression profiling, and mitochondrial content and function were analyzed using muscle and muscle cell cultures established from healthy and calpain-3-deficient mice. Calpain-3-deficient mice were also treated with PPAR-delta agonist (GW501516) to assess mitochondrial function and membrane repair. The unpaired t test was used to assess the significance of the differences observed between the two groups or treatments. ANOVAs were used to assess significance over time. Results We find that calpain-3 deficiency causes mitochondrial dysfunction in the muscles and myoblasts. Calpain-3-deficient myoblasts showed increased proliferation, and their gene expression profile showed aberrant mitochondrial biogenesis. Myotube gene expression analysis further revealed altered lipid metabolism in calpain-3-deficient muscle. Mitochondrial defects were validated in vitro and in vivo. We used GW501516 to improve mitochondrial biogenesis in vivo in 7-month-old calpain-3-deficient mice. This treatment improved satellite cell activity as indicated by increased MyoD and Pax7 mRNA expression. It also decreased muscle fatigability and reduced serum creatine kinase levels. The decreased mitochondrial function also impaired sarcolemmal repair in the calpain-3-deficient skeletal muscle. Improving mitochondrial activity by acute pyruvate treatment improved sarcolemmal repair. Conclusion Our results provide evidence that calpain-3 deficiency in the skeletal muscle is associated with poor mitochondrial biogenesis and function resulting in poor sarcolemmal repair. Addressing this deficit by drugs that improve mitochondrial activity offers new therapeutic avenues for LGMD2A.

scholarly journals Beneficial Effects on Brain Micro-Environment by Caloric Restriction in Alleviating Neurodegenerative Diseases and Brain Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Zhang ◽  
Huachong Xu ◽  
Ning Ding ◽  
Xue Li ◽  
Xiaoyin Chen ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Caloric Restriction ◽  
Metabolic Disorders ◽  
Brain Aging ◽  
Future Perspectives ◽  
Brain Health ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Extracellular Microenvironment

Aging and neurodegenerative diseases are frequently associated with the disruption of the extracellular microenvironment, which includes mesenchyme and body fluid components. Caloric restriction (CR) has been recognized as a lifestyle intervention that can improve long-term health. In addition to preventing metabolic disorders, CR has been shown to improve brain health owing to its enhancing effect on cognitive functions or retarding effect on the progression of neurodegenerative diseases. This article summarizes current findings regarding the neuroprotective effects of CR, which include the modulation of metabolism, autophagy, oxidative stress, and neuroinflammation. This review may offer future perspectives for brain aging interventions.

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