Further Evidence for Cellular Senescence to Contribute to Atrial Fibrillation
Senescent cells accumulate with age, and their secretions provoke chronic inflammation and tissue dysfunction. With this in mind, researchers have shown that cellular senescence correlates with atrial fibrillation in older people. Here is a more recent demonstration of this relationship. I'm not aware of a study that shows senolytic therapy to remove senescent cells is a useful treatment for atrial fibrillation, but evaluation of this approach seems a good idea, both in aged animal models and in human patients.
Atrial fibrillation (AF) is the most frequent arrhythmia in clinical practice and is closely associated with increased cardiovascular morbidity and mortality. Accumulating evidence has shown that the incidence and prevalence of AF increase with age. Moreover, aging is an important risk factor for AF recurrence. At the cellular level, aging is characterized by cellular senescence, a state of irreversible cell cycle arrest and loss of specialized cellular functions. Senescent cells accumulate with age; as a result of genotoxic stress or various chronic diseases, they contribute to tissue aging and have been implicated in age-related tissue dysfunction because of the accumulation of damaged cells at sites of tissue injury and remodeling.
Recently, researchers have investigated the link between AF and cell senescence, showing that endothelial or fibroblast senescence may pave the way for adverse atrial remodeling in AF by promoting proinflammatory, prothrombotic, and profibrotic responses. We sought to understand senescence in AF and the extent to which it aggravates the AF process. Twenty-six AF patients undergoing open-heart surgery were included, and 12 patients with sinus rhythm served as controls. Another cohort included 120 consecutive persistent AF patients with valvular heart diseases.
Compared with sinus rhythm, left atrial appendages (LAAs) with AF presented a significantly increased positive area of cellular senescence, with upregulated expression of p16, p21, and p53. Next, p21 mRNA was increased in patients with AF recurrence compared with that in patients without recurrence. Further, p21 was a significant independent predictor of AF early recurrence (odds ratio 2.97). This finding may help facilitate the search for new therapeutic approaches for antiaging therapy for AF.
It will be very hard to isolate the effects of a senolytic therapy since it would have synergetic benefits all over the body. A better liver might reduce the cholesterol burden. Better neurotransmitters might improve the heartbit. And so on.