RE: Mitochondrien - 16

Es wäre schon interessant zu sehen, wie signifikant die Lebensverlängerung wäre, die man mit neuen Mitochondrien erreichen könnte. Falls man die wirklich austauschen kann, wäre das vielleicht eine der ersten Maßnahmen zur Realverjüngung. Diese könnte eine ganze Kaskade von positiven Wirkungen nach sich ziehen, da Mitos ja auch an Seneszenz / Apoptose beteiligt sind: RE:News aus der Forschung 2023 (10)
Gerade die hohe Mutationsrate der Mito-DNA älterer Menschen (vorheriger Post) können einem schon zu denken geben.

Mitochondria pleiotropism in stem cell senescence: Mechanisms and therapeutic approaches

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Mitochondrial dysfunction has been increasingly recognized as a central player in the aging process. According to the mitochondrial free radical theory of aging, ROS are considered to be unwanted toxic by-products of aerobic metabolism that induce oxidative damage to various macromolecules (lipids, proteins, and nucleic acids) due to their high chemical reactivity [29]. This mitochondrial theory of aging is based on the fact that mitochondrial function declines with aging leading to ROS overproduction and the activity of several ROS-scavenging enzymes also declines with age. Further supporting this theory, it has been reported that mutations of mitochondrial DNA (mtDNA) accumulate during aging. Mutations of mtDNA may arise as a consequence of unrepaired DNA damage, such as damage caused by ROS, or by replication errors during normal mtDNA synthesis [30]. Interestingly, mtDNA mutations have been proposed as a driving force in aging, as demonstrated by the mutator mice displaying an accelerated aging phenotype [31]. Finally, the link between mitochondrial function and signalling pathways has been reported to regulate longevity since aging-associated phenotypes have been associated to altered mitochondrial function, biogenesis and metabolism [28].

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https://www.sciencedirect.com/b/s/scienc...891584923006433

Zitat von Prometheus im Beitrag #379

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-Maßnahmen gegen mutierte Mitochondrien? Mitophagie-Aktivierung!

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Dietary Mitophagy Enhancer: A Strategy for Healthy Brain Aging?

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Growing evidence indicates that curcumin, astaxanthin, resveratrol, hydroxytyrosol, oleuropein, and spermidine might exert protective functions via antioxidative properties and as well the enhanced induction of mitophagy mediators. The compounds seem to upregulate mitophagy and thereby alleviate the clearance of dysfunctional and aged mitochondria as well as mitogenesis.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600282/

Kommentar: Ich bin da inzwischen vorsichtig, mir zu große Hoffnungen zu machen was natürliche Stoffe angeht. Andererseits kann man sich ja mal inspirieren lassen, welche Pille man seiner Sammlung noch hinzufügen möchte.

The effect of fasting or calorie restriction on mitophagy induction: a literature review

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Current evidence overwhelmingly suggests that CR and fasting induce mitophagy and mitophagy‐related markers. Based on the current evidence that we reviewed here, it could be concluded that fasting or CR has a promising role as a novel and practical approach in the prevention of age‐related diseases without any side effects by inducing mitophagy in different organs of the body. More studies will be required in future to clarify the relationship between food deprivation and mitophagy. Further studies using a variety of different types of CR and fasting states are also warranted to determine the best approach for inducing mitophagy and improving health.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749612/

Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment
https://www.mdpi.com/1422-0067/25/14/7952

Urolithin A für die Mitophagie?

Granatapfelsaft (3)

Mitophagy Activation by Urolithin A to Target Muscle Aging

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During aging, mitophagy levels decline and negatively impact skeletal muscle performance. Nutritional and pharmacological approaches have been proposed to manage the decline in muscle function due to impaired mitochondria bioenergetics. The natural postbiotic Urolithin A has been shown to promote mitophagy, mitochondrial function and improved muscle function across species in different experimental models and across multiple clinical studies.

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https://pubmed.ncbi.nlm.nih.gov/37925671/

Targeting aging with urolithin A in humans: A systematic review

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Urolithin A (UA) is a gut metabolite derived from ellagic acid. This systematic review assesses the potential geroprotective effect of UA in humans. In five studies including 250 healthy individuals, UA (10–1000 mg/day) for a duration ranging from 28 days to 4 months, showed a dose-dependent anti-inflammatory effect and upregulated some mitochondrial genes, markers of autophagy, and fatty acid oxidation. It did not affect mitochondrial maximal adenosine triphosphate production, biogenesis, dynamics, or gut microbiota composition. UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function. Unrelated adverse events were mild or moderate.

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https://www.sciencedirect.com/science/ar...568163724002241

Urolithin-A Promotes CD8+ T Cell–mediated Cancer Immunosurveillance via FOXO1 Activation

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Urolithin-A (UroA) is a first-class metabolite activator of mitophagy successfully tested to treat age-related disease in both preclinical (11) and clinical settings (12–15). UroA exhibits anti-inflammatory properties, and potent metabolic modulation properties, suggesting its application to attenuate or prevent the onset of several diseases, including Alzheimer's disease, diabetes, and nephrotoxicity (14). In addition, UroA acts on both innate and adaptive immune cells (14) by attenuating inflammatory state of macrophages or neutrophils (16, 17), inhibiting pathogenicity of Th17 cells (18) and boosting T cells anticancer activity in colon and pancreatic preclinical models (19, 20).

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11067828/

Urolithin A Prevents Sleep-deprivation-induced Neuroinflammation and Mitochondrial Dysfunction in Young and Aged Mice

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Furthermore, UA also attenuated SD-induced mitochondrial dysfunction, normalized autophagy and mitophagy and protected hippocampal neuronal morphology.

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https://pubmed.ncbi.nlm.nih.gov/37725214/

Hat hier jemand mal Urolithin A probiert?

Mitochondria are flinging their DNA into our brain cells

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A new study finds that mitochondria in our brain cells frequently fling their DNA into the cells' nucleus, where the mitochondrial DNA integrates into chromosomes, possibly causing harm.

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https://www.sciencedaily.com/releases/20...40822142624.htm

N6-Methyladenine Progressively Accumulates in Mitochondrial DNA during Aging

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In this paper, we present a reliable, PCR-based method to determine accurately the relative 6mA levels in the mtDNA of Caenorhabditis elegans, Drosophila melanogaster and dogs, and show that these levels gradually increase with age. Furthermore, daf-2(−)-mutant worms, which are defective for insulin/IGF-1 (insulin-like growth factor) signaling and live twice as long as the wild type, display a half rate at which 6mA progressively accumulates in the mtDNA as compared to normal values. Together, these results suggest a fundamental role for mtDNA N6-adenine methylation in aging and reveal an efficient diagnostic technique to determine age using DNA.

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https://www.mdpi.com/1422-0067/24/19/14858

Chronic mitochondrial fragmentation elicits a neuroprotective Warburg-like effect in Drosophila neurons
https://www.biorxiv.org/content/10.1101/...tyz-oct_nicjnYw

Mitochondrial and Metabolic Differences Between Sedentary and Active Individuals at Rest and During Exercise: The Hidden Costs of Inactivity

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The study revealed a significant difference in the capacity of mitochondrial complexes between active individuals and sedentary individuals. Specifically, mitochondrial complex I capacity was 36% higher in active individuals compared to sedentary individuals, and complex II capacity was also elevated by 28% in active individuals. These findings suggest that active individuals have more powerful mitochondrial function at rest, which may contribute to greater energy efficiency and cellular resilience.

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https://gethealthspan.com/science/articl...ting-conditions

Mitochondrial direct repeat reduction as a strategy for enhancing human longevity: the case of the common repeat
https://www.biorxiv.org/content/10.1101/...mekztJK9jV7iGkA

SS-31 inhibits mtDNA-cGAS-STING signaling to improve POCD by activating mitophagy in aged mice

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Our study revealed that SS-31 interacted with PHB2 to activate mitophagy and improve neural damage in surgically aged mice, which was attributed to the reduced cGAS-STING pathway and M1 microglial polarization by decreased release of mitochondrial DNA (mtDNA) but not nuclear DNA (nDNA). In vitro, knockdown of PHB2 and an STING agonist abolished the protective effect of SS-31.

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https://pubmed.ncbi.nlm.nih.gov/38411634/

Application research of novel peptide mitochondrial-targeted antioxidant SS-31 in mitigating mitochondrial dysfunction

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As such, SS-31 may emerge as a viable choice for the treatment of mitochondrial dysfunction-related ailments in the foreseeable future. This article extensively expounds upon the superiority of SS-31 over natural antioxidants and traditional mitochondrial-targeted antioxidants, delves into its mechanisms of modulating mitochondrial function, and comprehensively summarizes its applications in alleviating mitochondrial dysfunction-associated disorders. Furthermore, we offer a comprehensive outlook on the expansive prospects of SS-31's future development and application.

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https://pubmed.ncbi.nlm.nih.gov/38237649/

Mild activation of the mitochondrial unfolded protein response increases lifespan without increasing resistance to stress
https://www.biorxiv.org/content/10.1101/...X3p7zLwtZWlLZWg

The State of the Mitochondria Portion of the Aging Biotech Field
https://docs.google.com/document/d/1G4f8...dit?usp=sharing

Atomic vacancies of molybdenum disulfide nanoparticles stimulate mitochondrial biogenesis
https://www.nature.com/articles/s41467-024-52276-8

Gemäß Endosymbiontentheorie waren Mitochondrien ursprünglich mal Bakterien, von daher kann man sich schon fragen, ob Antibiotika entsprechend einen negativen Effekt auf die Mitos haben könnten.

Do antibiotics cause mitochondrial and immune cell dysfunction? A literature review

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Different classes of antibiotics exert varying immunomodulatory and bioenergetic effects with more consistent findings reported for quinolones and macrolides. This variation may be partially explained by differences in study methodology, cell types studied and underlying disease. Most studies to date have used in vitro or animal models and clinical data are relatively scarce. In many of these studies, supratherapeutic antibiotic concentrations have been used so the relevance to clinically relevant dosing regimens remains uncertain. Nonetheless, recommendations to increase antibiotic dose and/or frequency in critically ill patients, e.g. for quinolones and piperacillin/tazobactam, allied with an impaired ability to metabolize/excrete antibiotics due to concurrent organ dysfunction, altered volumes of distribution and protein binding, and the widening use of combination therapies to cover potentially resistant organisms will enhance the risk of potential toxicity.

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https://academic.oup.com/jac/article/77/...933?login=false

Also von denen wird im obigen Text unter bestimmten Umständen abgeraten:
https://de.wikipedia.org/wiki/Chinolon-Antibiotika
https://de.wikipedia.org/wiki/Piperacillin
https://de.wikipedia.org/wiki/Tazobactam

Andererseits können gewisse andere Antibiotika (im Rundwurm) wohl auch lebensverlängernd wirken: Mitochondrien (14)
https://de.wikipedia.org/wiki/Doxycyclin
https://de.wikipedia.org/wiki/Azithromycin

Zu Chinolon-Antibiotika habe ich wirklich noch nie was Positives gelesen, vor allem zu Fluorchinolonen nicht:

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Fluorchinolone werden sowohl in der Humanmedizin als auch in der Veterinärmedizin eingesetzt. Da sie schwere, zum Teil irreversible Schäden am Nervensystem und Bewegungsapparat hervorrufen können, sind sie seit dem 8. April 2019 in Deutschland in der systemischen Anwendung eingeschränkt.[2] Trotz dieser Einschränkung geht der Einsatz von Fluorchinolonen nur langsam zurück.[3]

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https://de.wikipedia.org/wiki/Fluorchinolonantibiotikum

Astragalin ameliorates renal injury in diabetic mice by modulating mitochondrial quality control via AMPK-dependent PGC1α pathway

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We demonstrated that AG treatment modulated mitochondrial quality control and ameliorated apoptosis, boosting mitochondrial biogenesis, maintaining mitochondrial dynamic homeostasis, and improving energy metabolism disorder in vivo and in vitro. In high glucose and lipids-stimulated HK2 cells, we found that AG (20 μM) restored the phosphorylation level of AMPK, and upregulated the expression and transcriptional activity of PGC1α, whereas treatment with H2O2, blockade of AMPK with Compound C or knockdown of AMPKα with siRNA abolished the protective effect of AG on mitochondrial function, suggesting that antioxidant effects and activation of AMPK-dependent PGC1α pathway might be the molecular mechanisms underlying the protective effects of AG on mitochondrial quality control.

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https://pubmed.ncbi.nlm.nih.gov/36859596/

A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis

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Liver injury is the early stage of liver disease, which is caused by multiple factors. Baicalein has shown extensive bioactivity. But whether baicalein has a protective effect on liver injury has not been reported thus far. In this study, we aim to investigate the protective effects of baicalein on liver injury induced by oxidative stress. H2O2 and CCl4 were employed to establish liver injury models in vivo and in vitro, respectively. The protective effect of baicalein on oxidative stress-induced liver injury was evaluated by detecting the mitochondrial dynamics, the level of autophagy and apoptosis, the histopathology of liver, the indicators of liver function, and the level of oxidative stress in vitro and in vivo. March5 is the key regulator during liver injury induced by oxidative stress. March5 can ubiquitinate Drp1 and promote Drp1 degradation, then maintain the homeostasis of mitochondrial dynamics, keep the balance of autophagy, and reduce apoptosis. Baicalein is able to effectively reduce liver injury; it can contribute to the expression of March5 by regulating KLF4 during liver injury. These results indicate that baicalein plays a key role in salvaging liver from injury induced by oxidative stress via regulating the KLF4-March5-Drp1 signal pathway.

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https://pubmed.ncbi.nlm.nih.gov/32409930/

Baicalein scheint sogar relativ rein (85%) erhältlich zu sein: https://www.natuerlichlangleben.de/Baica...akt-Pulver-50-g
Den Shop kenne ich aber nicht. Bei vielen Flavonoiden zu denen man tolle Studien liest ist es ja leider so, dass sie dann kaum erhältlich sind bzw. bei Extrakten nur einen geringen Anteil dieser ausmachen.