RE: Mitochondrien - 15

Groundbreaking Research Unveils Role of Mitochondria in Dietary Lipid Processing
https://bnnbreaking.com/breaking-news/he...pid-processing/

A mitochondria-regulated p53-CCF circuit integrates genome integrity with inflammation
https://www.biorxiv.org/content/10.1101/2023.11.20.567963v1

MOTS-c reduces myostatin and muscle atrophy signaling

Zitat

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These results suggest that through inhibition of myostatin, MOTS-c could be a potential therapy for insulin resistance-induced skeletal muscle atrophy as well as other muscle wasting phenotypes including sarcopenia.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238132/

MOTS-c Functionally Prevents Metabolic Disorders

Zitat

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As a new member of the mitochondrial-derived peptide family, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is regarding a peptide hormone that could reduce insulin resistance, prevent obesity, improve muscle function, promote bone metabolism, enhance immune regulation, and postpone aging. MOTS-c plays these physiological functions mainly through activating the AICAR-AMPK signaling pathways by disrupting the folate-methionine cycle in cells. Recent studies have shown that the above hormonal effect can be achieved through MOTS-c regulating the expression of genes such as GLUT4, STAT3, and IL-10.
(...)
The tissue and circulating levels of MOTS-c fall with age; it is compelling to hypothesize that declining MDP levels are related to age-related metabolic deterioration. These mitochondrial genetic changes, we hypothesize, may contribute to the age-dependent decrease in MOTS-c levels.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866798/

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

Zitat

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Gradually disordered metabolic level is one of the signs of aging, which inhibit the normal physiological function of the body and even lose the ability to take care of themselves (27). The reality is that aging is a key risk factor for chronic diseases (28). Adaptation of cellular responses to changing internal and external environments is necessary for the health of an organism. Besides generating large amounts of cellular energy, mitochondria are closely related to aging, but the mechanism behind this phenomenon is unclear.

Studies have shown that the interaction of MOTS-c/NRF2 can improve the expression of mitochondrial protective genes (5, 28, 29). The aging process could lead to a decrease in MOTS-c levels (28, 29). In fact, MOTS-c levels in skeletal muscle and blood circulation in both humans and mice decrease with age. Studies have shown that blood MOTS-c levels in young people are 11% and 21% higher than those in middle- and old-aged people, respectively (30). In addition, different from animal experiments, the levels of MOTS-c in skeletal muscle of the elderly were the highest, indicating that the level of MOTS-c in plasma and muscle decreased gradually with age (30). This phenomenon may be attributed to the differential regulation of tissue specificity. Furthermore, the strong correlation between pathological results of different ages and the level of MOTS-c suggests that higher MOTS-c is beneficial to delaying aging.

---

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905433/

MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus

Zitat

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Multiple nuclear-encoded proteins have been known to regulate mitochondrial gene expression. On the contrary, no mitochondrial-encoded factors are known to actively regulate nuclear gene expression. MOTS-c (mitochondrial open reading frame of the 12S ribosomal RNA type-c) is a recently identified peptide encoded within the mitochondrial 12S ribosomal RNA gene that has metabolic functions. Notably, MOTS-c can translocate to the nucleus upon metabolic stress (e.g., glucose restriction and oxidative stress) and directly regulate adaptive nuclear gene expression to promote cellular homeostasis.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224472/

Mitochondria-derived peptides in aging and healthspan

Zitat

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In humans, circulating MOTS-c levels decrease with age, as does humanin. But unlike humanin, MOTS-c has been shown to increase its levels in skeletal muscle (89). Moreover, MOTS-c was found to have effects on lifespan itself. Reynolds et al. found that intraperitoneal administration of 15 mg/kg MOTS-c three times a week starting at 23.5 months of age caused a trend toward increased lifespan that did not quite reach significance (65). As with the lifespan study in humanin-treated mice, this lack of significant increase may have been due to a suboptimal dosing for a lifespan study and relatively short half-life of circulating MOTS-c. On the other hand, these mice did have significant improvement in grip strength, gait, and physical performance, demonstrating an increase in healthspan in MOTS-c–treated animals.

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https://www.jci.org/articles/view/158449

Als Übergangslösung bis man die epigenetische Reprogrammierung im Supermarkt kaufen kann neben anderen womöglich eine Betrachtung wert. Sehr interessant auch, dass dieses Mitochondrien-Peptid den Nukleus erreichen und dort Gene regulieren kann. Das zeigt, wie komplex der Vorgang, den wir Alterung nennen ist und wie viele Prozesse sich gegenseitig beeinflussen. Welche Strategie wäre da allgemein angebracht? So viele Faktoren wie möglich auf jugendlichem Niveau halten und schauen was an Alterung trotzdem noch stattfindet? So könnte man die Kernfaktoren der Alterung vielleicht einfacher identifizieren. Das wäre mal ein spannendes Mausexperiment.

Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation
https://www.sciencedirect.com/science/ar...300908424000361

Also ich frage mich ja seit Längerem, wieso GH lebensverkürzend wirkt. Möglicherweise ist das Mitochondrienpeptid Humanin die Ursache oder zumindest Teil davon:

IGF-I regulates the age-dependent signaling peptide humanin

Zitat

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Long-lived, GH-deficient Ames mice displayed elevated humanin levels, while short-lived GH-transgenic mice have reduced humanin levels. Furthermore, treatment with GH or IGF-I reduced circulating humanin levels in both mice and human subjects. Our results indicate that GH and IGF are potent regulators of humanin levels and that humanin levels correlate with lifespan in mice. This suggests that humanin represents a circulating mitochondrial signal that participates in modulating the aging process, adding a coordinated mitochondrial element to the endocrine regulation of aging.

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https://www.researchgate.net/publication...peptide_humanin

Positive Auswirkungen auf T scheint es auch zu geben:

Humanin Ameliorates Late-onset Hypogonadism in Aged Male Rats

Zitat

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Humanin might be a promising therapeutic modality in late-onset hypogonadism as it ameliorated some age-related testicular and hormonal adverse effects.

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https://pubmed.ncbi.nlm.nih.gov/35086467/

Lebensverlängernd?

The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan

Zitat

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Here we report that in C. elegans the overexpression of humanin is sufficient to increase lifespan, dependent on daf-16/Foxo. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence. Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer’s disease and MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343442/

Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

Zitat

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Treatment with humanin on mice is able to increase both their lifespan and health span. The mechanisms behind the protective effects of humanin in different diseases are slowly being unveiled and appear to be connected with autophagy and cytoprotective activity.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135985/

Ein recht umfangreicher Artikel mit weiterführenden Informationen: https://jaycampbell.com/peptides/humanin-the-peptide/

Hallo,

für die Lebensverlängerung ist u.a. die Qualitätskontrolle der Mitochondrien entscheidend. GH ist nicht "schädlich" und man sollte es immer zusammen mit dem komplexen System bewerten: einzelne Hormone sollte man i.d.R. nicht einnehmen. DHEA bildet hier bei einer Cortisol/DHEA Dysbalance evtl. eine Ausnahme.

Viele Grüße

Roger

Mechanism and role of mitophagy in the development of severe infection
https://www.nature.com/articles/s41420-024-01844-4

Mitochondrial S-adenosylmethionine deficiency induces mitochondrial unfolded protein response and extends lifespan in Caenorhabditis elegans
https://onlinelibrary.wiley.com/doi/full..._PIAWo7buFqobmk

MtDNA deletions and aging
https://www.frontiersin.org/articles/10....24.1359638/full

Zitat von version2 im Beitrag #353

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MOTS-c reduces myostatin and muscle atrophy signaling

Zitat

---

These results suggest that through inhibition of myostatin, MOTS-c could be a potential therapy for insulin resistance-induced skeletal muscle atrophy as well as other muscle wasting phenotypes including sarcopenia.

---

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238132/

MOTS-c Functionally Prevents Metabolic Disorders

Zitat

---

As a new member of the mitochondrial-derived peptide family, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is regarding a peptide hormone that could reduce insulin resistance, prevent obesity, improve muscle function, promote bone metabolism, enhance immune regulation, and postpone aging. MOTS-c plays these physiological functions mainly through activating the AICAR-AMPK signaling pathways by disrupting the folate-methionine cycle in cells. Recent studies have shown that the above hormonal effect can be achieved through MOTS-c regulating the expression of genes such as GLUT4, STAT3, and IL-10.
(...)
The tissue and circulating levels of MOTS-c fall with age; it is compelling to hypothesize that declining MDP levels are related to age-related metabolic deterioration. These mitochondrial genetic changes, we hypothesize, may contribute to the age-dependent decrease in MOTS-c levels.

---

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866798/

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

Zitat

---

Gradually disordered metabolic level is one of the signs of aging, which inhibit the normal physiological function of the body and even lose the ability to take care of themselves (27). The reality is that aging is a key risk factor for chronic diseases (28). Adaptation of cellular responses to changing internal and external environments is necessary for the health of an organism. Besides generating large amounts of cellular energy, mitochondria are closely related to aging, but the mechanism behind this phenomenon is unclear.

Studies have shown that the interaction of MOTS-c/NRF2 can improve the expression of mitochondrial protective genes (5, 28, 29). The aging process could lead to a decrease in MOTS-c levels (28, 29). In fact, MOTS-c levels in skeletal muscle and blood circulation in both humans and mice decrease with age. Studies have shown that blood MOTS-c levels in young people are 11% and 21% higher than those in middle- and old-aged people, respectively (30). In addition, different from animal experiments, the levels of MOTS-c in skeletal muscle of the elderly were the highest, indicating that the level of MOTS-c in plasma and muscle decreased gradually with age (30). This phenomenon may be attributed to the differential regulation of tissue specificity. Furthermore, the strong correlation between pathological results of different ages and the level of MOTS-c suggests that higher MOTS-c is beneficial to delaying aging.

---

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905433/

MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus

Zitat

---

Multiple nuclear-encoded proteins have been known to regulate mitochondrial gene expression. On the contrary, no mitochondrial-encoded factors are known to actively regulate nuclear gene expression. MOTS-c (mitochondrial open reading frame of the 12S ribosomal RNA type-c) is a recently identified peptide encoded within the mitochondrial 12S ribosomal RNA gene that has metabolic functions. Notably, MOTS-c can translocate to the nucleus upon metabolic stress (e.g., glucose restriction and oxidative stress) and directly regulate adaptive nuclear gene expression to promote cellular homeostasis.

---

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224472/

Mitochondria-derived peptides in aging and healthspan

Zitat

---

In humans, circulating MOTS-c levels decrease with age, as does humanin. But unlike humanin, MOTS-c has been shown to increase its levels in skeletal muscle (89). Moreover, MOTS-c was found to have effects on lifespan itself. Reynolds et al. found that intraperitoneal administration of 15 mg/kg MOTS-c three times a week starting at 23.5 months of age caused a trend toward increased lifespan that did not quite reach significance (65). As with the lifespan study in humanin-treated mice, this lack of significant increase may have been due to a suboptimal dosing for a lifespan study and relatively short half-life of circulating MOTS-c. On the other hand, these mice did have significant improvement in grip strength, gait, and physical performance, demonstrating an increase in healthspan in MOTS-c–treated animals.

---

https://www.jci.org/articles/view/158449

Als Übergangslösung bis man die epigenetische Reprogrammierung im Supermarkt kaufen kann neben anderen womöglich eine Betrachtung wert. Sehr interessant auch, dass dieses Mitochondrien-Peptid den Nukleus erreichen und dort Gene regulieren kann. Das zeigt, wie komplex der Vorgang, den wir Alterung nennen ist und wie viele Prozesse sich gegenseitig beeinflussen. Welche Strategie wäre da allgemein angebracht? So viele Faktoren wie möglich auf jugendlichem Niveau halten und schauen was an Alterung trotzdem noch stattfindet? So könnte man die Kernfaktoren der Alterung vielleicht einfacher identifizieren. Das wäre mal ein spannendes Mausexperiment.

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MOTS-c soll sich bei mindestens 5 mg laut einiger weniger Erfahrungsberichte (experimentelle natürlich gemeint) auch sehr deutlich positiv auf Long Covid Fatigue auswirken. Anzunehmen dass dies auch auf SS-31 dann zutreffen wird.

Zitat von Speedy im Beitrag #361

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Anzunehmen dass dies auch auf SS-31 dann zutreffen wird.

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Zitat von version2 im Beitrag #362

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Zitat von Speedy im Beitrag #361

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Anzunehmen dass dies auch auf SS-31 dann zutreffen wird.

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Naja, nicht unbedingt, da die unterschiedlich sind. Generell natürlich die Frage, ob das beides nicht reine Symptombehandlung wäre, wenn das eigentliche Problem bei Long Covid Virenfragmente sind.

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Zitat von Speedy im Beitrag #363

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Ja schon aber eine dadurch bedingte mitochondriale Dysfunktion anzugehen ist dennoch wichtig. Wer trotz Long Covid sehr intensiv Exercise betreibt profitiert aber natürlich nicht wirklich von externem MOTS-c.

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Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons
https://www.nature.com/articles/s42255-0...QoCG044Y23xGBPo

Zitat von version2 im Beitrag #364

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Zitat von Speedy im Beitrag #363

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Ja schon aber eine dadurch bedingte mitochondriale Dysfunktion anzugehen ist dennoch wichtig. Wer trotz Long Covid sehr intensiv Exercise betreibt profitiert aber natürlich nicht wirklich von externem MOTS-c.

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Intensiv Sport betreiben stelle ich mir bei Long Covid kontraproduktiv vor. Virenfragmente beseitigen und Immunsystem regenerieren wären definitiv meine Prioritäten. Bist du denn noch betroffen oder wie?

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Zitat von Speedy im Beitrag #148

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An old medicine as a new drug to prevent mitochondrial complex I from producing oxygen radicals
https://journals.plos.org/plosone/articl...al.pone.0216385

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Mitochondrial Dysfunction as the Major Basis of Brain Aging
https://www.mdpi.com/2218-273X/14/4/402

Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA
https://www.nature.com/articles/s41467-0...cYjXXz3hS0hcARs

Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging
https://www.biorxiv.org/content/10.1101/...9dhzdFGmfLi3jx3

Zitat von Speedy im Beitrag #370

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Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging
https://www.biorxiv.org/content/10.1101/...9dhzdFGmfLi3jx3

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Zitat

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Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soybeans, from which they are mechanically or chemically extracted using hexane. They are also a member of the lecithin group of yellow-brownish fatty substances occurring in animal and plant tissues.

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https://en.wikipedia.org/wiki/Phosphatidylcholine

Also: Untergruppe der Lecithine, mit Hexan extrahiert. Hexan soll ungesund sein, da würde ich bei der Wahl des Supplements aufpassen, dass ein Prozess ohne Hexan genutzt wird.

Sehr ausführliches Paper dazu.

Mitochondrial dysfunction: mechanisms and advances in therapy
https://www.nature.com/articles/s41392-024-01839-8

Mitochondria at the crossroads of health and disease
https://www.cell.com/cell/fulltext/S0092...x_xb-Lk2-j9zQmf

Rhodamine 19 Alkyl Esters as Effective Antibacterial Agents
https://www.mdpi.com/1422-0067/25/11/6137

Overexpression of mitochondrial fission or mitochondrial fusion genes enhances resilience and extends longevity
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.14262