Researchers here argue that fibrosis of cardiac tissue is an important contribution to the development of atrial fibrillation in older patients. Fibrosis is a feature of many age-related conditions, a dysfunction in tissue maintenance processes that involves the generation of scar-like deposits of collagen by overactive fibroblasts. This scarring disrupts normal tissue structure and function in many organs, including the heart, and there is no good approved therapy to treat the progression of fibrosis: even slowing it is haphazard and unreliable.
This may soon change. Fibrosis appears to be caused to a large degree by the accumulation of lingering senescent cells. These errant cells are highly disruptive to tissue maintenance through inflammatory and other types of signaling. The development of senolytic therapies to selectively destroy senescent cells is well underway, and has been shown to reverse fibrosis in animal models. Some of the first human trials, using a combination of the generic drug dasatinib and supplement quercetin, are focused on fibrotic diseases such as idiopathic pulmonary fibrosis. Given continued success, this senolytic therapy should certainly be trialed as a means to treat fibrosis in other organs.
Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with high morbidity and mortality. It is well known that both the prevalence and incidence of AF increase sharply with age, particularly after 65 years of age. AF and aging share mutual bidirectional relationships. On the one hand, aging and aging-related underlying diseases result in myocardial remodeling that may lead to cardiac electrical abnormalities which enhance the occurrence or persistence of AF. On the other hand, AF worsens biological aging, specifically at the brain level, causing injuries related to ischemic and non-ischemic events, thereby impairing functional capacity. In addition, handling of AF is challenging in aged patients due to the high prevalence of complex clinical features (i.e. heart failure [HF] and chronic kidney disease) and the progressive AF-mediated aggravation of degenerative processes typical of aging. All these aspects have profound effects on the patient health condition and on the resources provided by the society and national health systems to dedicate to the care of elderly patients.
Even though it is well known that age is the single most important determinant of AF risk, the underlying mechanisms are not completely understood. Some of the mechanisms involved in the aging-AF association may be related with age-dependent left atrial dilation or senile amyloidosis that alter the structure of the myocardial tissue and constitute typical features of the so-called AF substrate. In addition, resting membrane potential depolarization and spontaneous calcium releases from the sarcoplasmic reticulum, among others, might promote afterdepolarization and trigger AF. Since fibrosis is a prominent lesion present in the atria of AF patients and atrial fibrosis can both affect the substrate and induce the trigger, this lesion emerges as a factor that may play a central role in aging-related AF. In particular, by increasing the severity of atrial fibrosis, age may contribute to the development of electrical conduction disturbances and ectopic activity, affecting atrial arrthythmogenity.