Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion … in space, 2025, Moreno-Villanueva+

Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space
Moreno-Villanueva, Maria; Jimenez-Chavez, Luis E.; Krieger, Stephanie; Ding, Liang-Hao; Zhang, Ye; Babiak-Vazquez, Adriana; Berres, Mark; Splinter, Sandra; Pauken, Kristen E.; Schaefer, Brian C.; Crucian, Brian E.; Wu, Honglu

INTRODUCTION
The impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.

METHODS
In this study, blood from eleven crewmembers was collected before and during International Space Station (ISS) missions. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using RNAsequencing. Differentially expresses genes (DEG) in space were determined by comparing of the inflight to the preflight samples. Pathways and statistical analyses of these DEG were performed using the Ingenuity Pathway Analysis (IPA) tool.

RESULTS
In comparison to pre-flight, a total of 2030 genes were differentially expressed in PBMC collected between 135 and 210 days in orbit, which included a significant number of surface receptors. The dysregulated genes and pathways were mostly involved in energy and oxygen metabolism, immune responses, cell adhesion/migration and cell death/survival.

DISCUSSION
Based on the DEG and the associated pathways and functions, we propose that mitochondria dysfunction was caused by constant modulation of mechano-sensing receptors in microgravity, which triggered a signaling cascade that led to calcium overloading in mitochondria. The response of PBMC in space shares T-cell exhaustion features, likely initiated by microgravity than by infection. Consequences of mitochondria dysfunction include immune dysregulation and prolonged cell survival which potentially explains the reported findings of inhibition of T cell activation and telomere lengthening in astronauts.

CONCLUSION
Our study potentially identifies the upstream cause of mitochondria dysfunction and the downstream consequences in immune cells.

Link | PDF (Frontiers in Immunology) [Open Access]

 

Not having experienced microgravity, many of the problems mentioned here seem to be present in ME/CFS too.
Is there a scientist looking at the connection?

 

I think POTS has been observed in Astronauts coming back from space after zero gravity.

That’s why the test is called the “NASA” tilt test.

 

Apart from the thing mentioned by Yann above, I think there have been a few looking at connections.

Rob Wüst has done research together with ESA as far as I recall. Naviaux also has done work with astronauts if I remember correctly. There's also been some "EBV reactivation" research for astronauts often quoted in ME/CFS research.

 

Are there known connections going the other way? It’s good to learn from other fields, but even better if those fields become interested in ME/CFS because it might benefit their work.

 

When what astronauts experiece would have been called space-ME/CFS would they have been called malingerers and everyone pointing at their heads; must be psychological?
Could astronauts help us with better press coverage if NASA adopted space-ME/CFS to describe their experiences.

 

I doubt it.

The astronauts all go back to "normal" after having experienced certain circumstances. The BPS theory is not that ME/CFS-like symptoms can't start following certain circumstances (a viral infection or similar) but that in ME/CFS patients symptoms persist due to malingering thoughts ("they keep holding onto their symptoms following a viral infection").

If astronauts would continue to have ME/CFS-like symptoms, then BPS propents could come in to play to say, "it's all in their head". But they don't seem to, so the comparison doesn't work. In fact they might say astronauts are exactly those people that wouldn't develop ME/CFS.

 

Type A for Astronaut?

 

I might be more optimistic. Astronauts had ME/CFS symptoms, but the general public doesn't know that.
The first time @SNT Gatchaman posted several treads on astronauts, I was new here and called for help. So much in common.
Others already knew for a while.

One of our astronauts André Kuipers, a doctor, had a bad bout of OI for several months (2 missions, 203 days).

Maybe we need an astronaut as ambassador.