A possible role for mitochondrial-derived peptides humanin and MOTS-c in patients with Q fever fatigue syndrome and CFS (Raijmakers et al 2019)

[Murph]

J Transl Med. 2019 May 14;17(1):157. doi: 10.1186/s12967-019-1906-3.
A possible role for mitochondrial-derived peptides humanin and MOTS-c in patients with Q fever fatigue syndrome and chronic fatigue syndrome.
Raijmakers RPH1,2, Jansen AFM3,4, Keijmel SP3,4, Ter Horst R4, Roerink ME4, Novakovic B5,6, Joosten LAB3,4,7, van der Meer JWM3,4, Netea MG3,4,7, Bleeker-Rovers CP3,4,7.
Author information

Abstract
BACKGROUND:
Q fever fatigue syndrome (QFS) is a well-documented state of prolonged fatigue following around 20% of acute Q fever infections. It has been hypothesized that low grade inflammation plays a role in its aetiology. In this study, we aimed to identify transcriptome profiles that could aid to better understand the pathophysiology of QFS.
METHODS:
RNA of monocytes was collected from QFS patients (n = 10), chronic fatigue syndrome patients (CFS, n = 10), Q fever seropositive controls (n = 10), and healthy controls (n = 10) who were age- (± 5 years) and sex-matched. Transcriptome analysis was performed using RNA sequencing.
RESULTS:
Mitochondrial-derived peptide (MDP)-coding genes MT-RNR2 (humanin) and MT-RNR1 (MOTS-c) were differentially expressed when comparing QFS (- 4.8 log2-fold-change P = 2.19 × 10-9 and - 4.9 log2-fold-change P = 4.69 × 10-8), CFS (- 5.2 log2-fold-change, P = 3.49 × 10-11 - 4.4 log2-fold-change, P = 2.71 × 10-9), and Q fever seropositive control (- 3.7 log2-fold-change P = 1.78 × 10-6 and - 3.2 log2-fold-change P = 1.12 × 10-5) groups with healthy controls, resulting in a decreased median production of humanin in QFS patients (371 pg/mL; Interquartile range, IQR, 325-384), CFS patients (364 pg/mL; IQR 316-387), and asymptomatic Q fever seropositive controls (354 pg/mL; 292-393).
CONCLUSIONS:
Expression of MDP-coding genes MT-RNR1 (MOTS-c) and MT-RNR2 (humanin) is decreased in CFS, QFS, and, to a lesser extent, in Q fever seropositive controls, resulting in a decreased production of humanin. These novel peptides might indeed be important in the pathophysiology of both QFS and CFS.

 

[msf]

I've definitely not felt like a humanin much since I got ME. Does anyone know what this substance does?

 

[ljimbo423]

I've definitely not felt like a humanin much since I got ME. Does anyone know what this substance does?

Research
Experiments using cultured cells have demonstrated that humanin has both neuroprotective as well as cytoprotective effects and experiments in rodents have found that it has protective effects in Alzheimer's disease models, Huntington's disease models and stroke models.[13]

Humanin is proposed to have myriad neuroprotective and cytoprotective effects. Both studies in cells and rodents have both found that administration of humanin or humanin derivatives increases survival and/or physiological parameters in Alzheimer's disease models.[14][15]

In addition to Alzheimer's disease, humanin has other neuroprotective effects against models of Huntington's disease, prion disease, and stroke.[16][17][18] Beyond the possible neuroprotective effects, humanin protects against oxidative stress, atherosclerotic plaque formation, and heart attack.[19][20][21][22]

Metabolic effects have also been demonstrated and humanin helps improve survival of pancreatic beta-cells, which may help with type 1 diabetes,[23] and increases insulin sensitivity, which may help with type 2 diabetes.[24] In rats, the humanin analog appears to normalize glucose levels and reduce diabetes symptoms.[25]

Rattin shows the same ability as humanin to defend neurons from the toxicity of beta-amyloid, the cause of degeneration in Alzheimer's Disease.[6]

Small humanin-like peptides are a group of peptides found in the mitochondrial 16S rRNA, and also possess retrograde signaling functions.

link

 

[delphis]

what would happen if a cfs patient supplemented with mots-c peptide injections?

 

[GlassHouse]

Interesting! I actually had brucellosis (Q fever), which had to be reported to the CDC when the blood results came in. But it was only one of many viral and bacterial infections I had.

 

[pattismith]

MT-RNR1: Regulates insulin sensitivity and metabolic homeostasis. Inhibits the folate cycle, thereby reducing de novo purine biosynthesis which leads to the accumulation of the de novo purine synthesis intermediate 5-aminoimidazole-4-carboxamide (AICAR) and the activation of the metabolic regulator 5'-AMP-activated protein kinase (AMPK). Protects against age-dependent and diet-induced insulin resistance as well as diet-induced obesity. {ECO:0000269|PubMed:25738459}

Disease: Deafness, Nonsyndromic Sensorineural, Mitochondrial"

Interesting! I actually had brucellosis (Q fever), which had to be reported to the CDC when the blood results came in. But it was only one of many viral and bacterial infections I had.

Actually Brucellosis comes from a brucella bacteria, it's not Q Fever. Q fever, also called query fever, is a bacterial infection caused by the bacteria Coxiella burnetii. (Both Brucellosis and Q Fever comes from infected animals )

 

[GlassHouse]

MT-RNR1: Regulates insulin sensitivity and metabolic homeostasis. Inhibits the folate cycle, thereby reducing de novo purine biosynthesis which leads to the accumulation of the de novo purine synthesis intermediate 5-aminoimidazole-4-carboxamide (AICAR) and the activation of the metabolic regulator 5'-AMP-activated protein kinase (AMPK). Protects against age-dependent and diet-induced insulin resistance as well as diet-induced obesity. {ECO:0000269|PubMed:25738459}

Disease: Deafness, Nonsyndromic Sensorineural, Mitochondrial"


Actually Brucellosis comes from a brucella bacteria, it's not Q Fever. Q fever, also called query fever, is a bacterial infection caused by the bacteria Coxiella burnetii. (Both Brucellosis and Q Fever comes from infected animals )

You’re right! I’m mixing up my sheep illnesses. It’s been a while since my animal science days in college.

I did not have Q fever, I had brucellosis. I also had
tularemia. My animal exposure was very high since I did years of veterinary nurse work throughout high school and college, including in third-world countries, with both small and large animals

 

[Gemini]

J Transl Med. 2019 May 14.
A possible role for mitochondrial-derived peptides humanin and MOTS-c in patients with Q fever fatigue syndrome and chronic fatigue syndrome.

Thanks for posting this interesting study @Murph. A Q Fever expert is moderating the Feb 13, 2020 CDC Conference Call.

This paper references the IOM Report and Naviaux's and Nakatomy's research:

[exerpts}

it could be argued that these peptides are important in the pathophysiology of both CFS and QFS [26, 27, 29]. Their role in cell metabolism supports the hypothesis that chronic fatigue might result from a hypometabolic state [35–37].

It has long been thought that mitochondrial pathology underlies chronic fatigue aetiology, as one of the key features of mitochondrial disease is severe fatigue [36, 38–41].

Other than its role in regulating metabolism, humanin also serves as a neuroprotective factor that could potentially influence neuroinflammation by downplaying activation of microglia. This would fit with the PET-CT study by Nakatomy et al. in which CFS patients show signs of neuroinflammation [42] A decreased expression of humanin might very well lead to the neuroinflammatory processes that were seen in these patients.

These processes might explain the neurocognitive problems, e.g., memory loss, impaired concentration, etc., these patients often concomitantly experience [6].

MOTS-c is also known to regulate muscle metabolism and has been implicated in the regulation of exercise [27]. A deficiency of this peptide might therefore be involved in common complaints of muscle ache and exercise intolerance in CFS and QFS.

[my bold and paragraphing]

 

[ShepherdK]

Interesting - MOTS-C and Humanin have started popping up on peptide research websites. PeptideSciences and CanLab both offer MOTS-C and Humanin, although the cost is relatively high + can only be administered through injection. Looks like people are starting to experiment with these peptides as well.

Anecdotal Reports:

• Fitness / biohacker talking about MOTS-C, peptide stability, and studied effects of the substance. He speculatively claims 10mg once a week ($150/week) may help correct metabolic disorders, while 1mg once a week would help individuals in an anti-aging stack.
• Healthy Reddit user who claims MOTS-C gives them more energy.

Interesting to note that increased MOTS-C/humanin levels are carcinogenic by nature. Cancer cells often upregulate these genes in order to accomodate unchecked growth. There is one paper that does note that humanin supplementation alongside chemotherapy did not change the effectiveness of the chemo therapy, so who knows the real risk here. Tangential question: Do we know whether ME/CFS patients develop cancer at a reduced rate compared to healthy control populations?

 

[sb4]

Do we know whether ME/CFS patients develop cancer at a reduced rate compared to healthy control populations?

Ive always thought we would have increased risk of cancer due to warburg metabolism and I remember reading here that CFS patients had increased heart disease / cancer but I don't have anything to back this up.