Aging and sinus node dysfunction: mechanisms and future directions

Aging is a natural biological process influenced by endogenous and exogenous factors such as genetics, environment, and individual lifestyle. The aging-dependent decline in resting and maximum heart rate is a conserved feature across multiple species, including humans. Such changes in heart rhythm control underscore fundamental alterations in the primary cardiac pacemaker, the sinoatrial node (SAN). Older individuals often present symptoms of SAN dysfunction (SND), including sinus bradycardia, sinus arrest, and bradycardia-tachycardia syndrome. These can lead to a broad range of symptoms from palpitations, dizziness to recurrent syncope. The sharp rise in the incidence of SND among individuals over 65 years old, coupled with projected longevity over the next decades, highlights the urgent need for a deeper mechanistic understanding of aging-related SND to develop novel and effective therapeutic alternatives. In this review, we will revisit current knowledge on the ionic and structural remodeling underlying age-related decline in SAN function, and a particular emphasis will be made on new directions for future research.