Aging and atrial fibrillation: a matter of fibrosis

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 [1]. 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 socalled AF substrate [2]. In addition, resting membrane potential depolarization and spontaneous calcium releases from the sarcoplasmic reticulum, among others, might promote afterdepolarization and trigger AF [3]. 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 [1]. Myocardial fibrosis is characterized not only by an excessive accumulation of collagen fibers (namely, type I fibers) in the interstitial space but also by an increased insolubility and stiffness of the deposited fibers due to an exaggerated degree of intermolecular covalent linkage, or cross-linking within these fibers. It has been reported that HF patients carrying simultaneously these Editorial