Mitochondrial Dysfunction as a Cause of Atrial Fibrillation

For any given age-related condition, you will find papers in the literature that focus on one mechanism of aging and its contribution to that condition. Usually these are reviews covering the details of the mechanism and how it causes pathology, or the epidemiology of the mechanism in the field, as absent an effective means of intervention it is very challenging to establish just how large a contribution that mechanism actually has.

While looking through the work here on age-related mitochondrial dysfunction and atrial fibrillation, it is worth also taking a look at past work on senescent cell burden as a cause of atrial fibrillation, potentially via inflammatory, pro-growth signaling that leads to fibrosis in heart tissue. In both cases there are approaches to addressing the issue, mitochondrial replacement and senolytic drugs to destroy senescent cells, but those assessments have yet to be carried out rigorously. Until they have one, there is no way to predict which of these contributing causes is more or less important than the other.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and contributes to a high prevalence of mortality and morbidity. The shortening of telomere length has been found to be common with age. Research efforts have argued that leukocyte telomere length (LTL) shortening is related to a variety of cardiovascular diseases, including atherosclerosis, left ventricular hypertrophy, and heart failure, but the relevance to AF is still controversial. In the Cardiovascular Health Study, researchers found no relationship between mean telomere length and AF in human atrial tissue.

The mechanisms of AF remain incompletely understood. Mitochondria play an important role in oxidative stress, calcium homeostasis, and energy metabolism. Studies have shown that mitochondrial dysfunction can cause insufficient ATP production and excessive reactive oxygen species (ROS), which damages the homeostasis of Ca2+ in myocardial cells and the excitability of membranes, in turn leading to AF.

Accumulating evidence has argued that PGC-1α is a key molecule of mitochondrial function because it participates in the regulation of mitochondrial biogenesis and energy metabolism and is closely related to oxidative stress and inflammation. It plays an important role in the occurrence and development of atherosclerosis, coronary heart disease, heart failure, and other cardiovascular diseases. Some researchers have put forward the concept of a "telomere-p53-PGC axis": that is, that the shortening of telomere will activate p53 expression, thereby inhibiting PGC-1 and causing mitochondrial dysfunction.

We measured the LTL, telomere-associated molecules, and mitochondrial membrane potential (MMP) of leukocytes to ascertain if they are correlated with aging-related AF and if they could be used as novel biomarkers for it. We found that LTL and serum PGC-1α are inversely correlated with the occurrence of aging-related AF and that the MMP of AF patients was significantly decreased, indicating that mitochondrial dysfunction plays a role.



Yeah but we already know all of these ... what's your next article ? Senescent cells are bad ? Caloric restriction increase lifespan by few years ? We know that since maybe 30 or 40 years ... we won't go to 150 and above with these beginner tools ...

Posted by: youssef at May 28th, 2021 7:42 AM

This IS Turbuckle's mitochondrial fission/fusion protocol over on the Longecity forums that I am doing this summer. I'll let you guys know how it goes for me.

I did the previous one early last year and really started "feeling my oats" right about the time of the first covid shutdown, which made me utterly incorrigible around my co-workers at the time. The shutdown didn't affect my work at all (I am an automation/control system integrator) and I was, in fact, pulling 10-12 hour days integrating some equipment at the time.

Posted by: Abelard Lindsey at May 28th, 2021 10:10 AM
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