Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans, 2025, Rodrigues+

Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans
Rodrigues, Kameron B.; Weng, Ziming; Graham, Zachary A.; Lavin, Kaleen; McAdam, Jeremy; Tuggle, S. Craig; Peoples, Brandon; Seay, Regina; Yang, Sufen; Bamman, Marcas M.; Broderick, Timothy J.; Montgomery, Stephen B.

Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear.

To study these, 10 healthy individuals were randomized to a 12-wk exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD). Blood plasma was collected pre- and postexercise at weeks 0 and 12 and after 4 wk of detraining upon program completion. Whole-genome enzymatic methylation sequencing (EM-seq) with cell-type proportion deconvolution was applied to cfDNA obtained from the 50 plasma samples and paired to concentration measurements for 90 circulating cytokines.

Acute exercise increased the release of cfDNA from neutrophils, dendritic cells (DCs), and macrophages proportional to exercise intensity. Exercise training reduced cfDNA released in HITT participants but not TRAD and from DCs and macrophages but not neutrophils. For most participants, training lowered mitochondrial cfDNA at rest, even after detraining. Using a sequencing analysis approach we developed, we concluded that rapid ETosis, a process of cell death where cells release DNA extracellular traps, was the likely source of cfDNA, demonstrated by enrichment of nuclear DNA. Further, several cytokines were induced by acute exercise, such as IL-6, IL-10, and IL-16, and training attenuated the induction of only IL-6 and IL-17F. Cytokine levels were not associated with cfDNA induction, suggesting that these cytokines are not the main cause of exercise-induced cfDNA.

Overall, exercise intensity and training modulated cfDNA release and cytokine responses, contributing to the anti-inflammatory effects of regular exercise.


SIGNIFICANCE
We present a whole-genome view of the cellular origins of cell-free DNA (cfDNA) in humans induced by exercise and how these origins are influenced by exercise intensity and training. We find evidence supporting acute exercise causing rapid, nuclear ETosis in neutrophils, dendritic cells (DCs), and macrophages. By simultaneously analyzing major inflammatory cytokines, we conclude that major cytokines are not the main trigger for cfDNA release during exercise, indicating that other factors may instead induce cfDNA release. Additionally, exercise training decreased cfDNA release in DCs and macrophages, but not neutrophils. This implies that exercise training reduces the inflammatory potential of DCs and macrophages, having significance for inflammation in diverse contexts such as aging, cancer, autoimmunity, and vaccination.


Link | PDF (Proceedings of the National Academy of Sciences)

 

Oh dear I was told that a virus is a piece of DNA without a cell and so I had assumed that any cell-free DNA is a virus

Spoiler: so my view was

so my view was that cell-free DNA is a virus and a virus is a cell-free DNA, and then I always wondered where all the survivng viral DNA had escaped from, from which cells, and if a virus can carry and transmit the genetic characteristics of it's source eg the nesting colonising habits of a rat or the roaming pack-hunting habits of a dog.

Likewise the research conclusion that a baby rat is born knowing genetically what the mother rat was taught

These scientists in 2024 knew that exercise triggers some intense inflammation but they didn't know how, and still don't

They also knew in 2024 that exercise also triggers the release of cellular DNA from its cell, so they also wanted to trace the source of escaped DNA, back to whichever destroyed cells it had escaped from

And also they wanted to learn ?[how molecules cause this release]? and what a released DNA is doing with our immunity

Spoiler: a synopsis of this researched presentation

By 2025 they had found out that such inflammation is not caused by the DNA released from its cells during exercise (to float around and be found in the plasma so presumably its transferred in blood transfusions so...)

Their research decided that question - its not the escaped DNA inflaming the tissues upon exercise (if it were this would have arisen after blood-typed blood transfusion, I would have thought, but now we know, I think, that a blood transfusion may include escaped DNA on the loose in the blood from a pulverised cell)

I don't get what are the chromosomal origins being modified - maybe its meant to mean training etc VARIES the type of exercised cell being either pulverised or not pulverised or less pulverised to release its DNA ?

Do they read too much into their loose association of the concurrent impacts on cytokines and DNA-release, but without full comparative measures to correlate a bean ?

Then claim too much, reckless of potential for harm ???

Implications are that training will remedy the poor resistance and tolerance for exercise attributed to inflammation, and therefore also remedy some of the other inflamed problems of aging, cancer, auto-immunity and post-vaccination. A good advert for a lot of rehab contracts

But they start out asking if loose DNA causes the inflammation then wind up saying it doesn't but inflammation doesnt cause the loose DNA

Spoiler: Then they seem to conflate some things

Then they seem to conflate some things

They say its good to reduce the inflammation by training, and as training also reduces the loose DNA so for some mysterious reason its also beneficial to reduce the DNA by training

But training doesnt reduce the IL-10 and IL-16 cytokines as measured and its not distinctly clear how reducing some but not all cytokines reduces the total pro-inflammatory potential of some cells ... I think they may mean it reduces the inflammatory potential of some training.

Isnt it nice to begin to see the effects of some previous discovery that training has an inflammatory potential which can vary within and between individuals

My understanding was that exercise and training can rip muscle to make it re-grow bigger which is beneficial to a point without steroidal enhancement and even more DNA released. I now suspect that people have various variable thresholds beyond which muscle is best not ripped further, eg once its adequately ripped or if ill then maybe unable to regrow etc

Although only "most" people will get the benefit claimed, the Significance concludes, maybe for the blinded and bamboozled, its for the good of all. Or am I being unfair ???

Spoiler: I think this Academy was

I think this Academy was one of those Academies convened in the USA for the combined expertise to tell the state and estate insurers the bounds of Long Covid entitlements, fully intent upon ensuring that all in need are included, so thats what David Putrino will be making sure of (see his 2024 TED talk on video in - maybe in the USA news thread

Now this Academy is publishing its 2025 Proceedings - I think thats the papers presented at some Symposium

Its the released mitochondrial DNA they found less of after some training, but only in "most" people. In the abstract they won't say how many is "most". But notably in some people they found no less so not everyone benefited in this way as claimed for the training program. I don't know if those who didn't benefit showed the usual problems of less not more resistance or tolerance for exercise

Also I've no idea where the mitochondrial DNA popped up from in the abstract, after referring only to which cell types are or are not or are less pulverised by which exercise.

I wonder if the British Society for Physiotherapy and Rehabilitation Medicine took this kind of thing into account April-Oct 2024 when researching in ?Blackpool? to help evidence the 2025 NHS rollout (UK)

- being the parent org of the Clinicians for Post Covid Society and I think subsequently recommending to all Britain's GPs that they all refer Long Covid cases for rehabilitation I suppose like: the survivors without Long Covid can have rehab, so why not and all that endorsed by Long Covid SOS on a patient participation contract (see the Long Covid SOS Thread)

Spoiler: I am left with the question

I am left with the question is it possible to devise micro-training for a regular micro-exercise to reduce the inflammation (or should that have said to reduce the increase of inflammation ??? aaarrrgghh)...

... a regular micro-exercise to reduce (modulate) the inflammations that may otherwise be increased (modulated) by any more intense and prolonged exercise (of muscle and its sensory-motor nerves and the blood-supply to nerve and muscle, and the nerves to the motor control of the dimensions of the blood vessels to regulate this blood supply ) ?

Eek. Thats an intricate combo to clunkily intervene in and with such intense force. No wonder its so easily reset beyond recovery once in disarray but then interfered with further

And who may not be benefited by training to decrease loose DNA tho what is the benefot of less loose DNA isn't at all clear since its not less inflammatiom

And who may be harmed, if given permission to do harm, and deemed ethical

Are the desensitising rehab theories aware that there may be inflammation involved ? Provoked and challenged.

As for exercising the blood supply, tissues and receptors signalling, light and sound and touch and pain.

For exercising my gut I know exactly how much of what when and how often is optimal that is safe and can be recovered from in good time for the next necessary meal, so no question of retraining, though a gut might need a relief from challenge to settle down and restore normal reactivity but without starving tissues thereto. So might a muscle, and maybe with oxygen starvation thrown in

So is this paper being wrongly cited and recited and re-re-cited by rehab theorists in the fields of ME/CFS and LC and government rollouts for the post-pandemic back to health and work programs which deny the scale of the Long Covid to the point that the denial is driving its victims towards their deaths

 

I don't think so. The abstract sounds like they didn't really learn all that much, but are making lots of unsupported conclusions that various groups will like (to abuse).