Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes

Gaetano Santulli, Guido Iaccarino

G protein-coupled receptors (GPCRs) play a key role in cellular communication, allowing human cells to sense external cues or to talk each other through hormones or neurotransmitters. Research in this field has been recently awarded with the Nobel Prize in chemistry to Robert J. Lefkowitz and Brian K. Kobilka, for their pioneering work on beta adrenergic receptors (βARs), a prototype GPCR. Such receptors, and β2AR in particular, which is extensively distributed throughout the body, are involved in a number of pathophysiological processes. Moreover, a large amount of studies has demonstrated their participation in ageing process. Reciprocally, age-related changes in regulation of receptor responses have been observed in numerous tissues and include modifications of βAR responses. Impaired sympathetic nervous system function has been indeed evoked as at least a partial explanation for several modifications that occur with ageing. This article represents an updated presentation of the current knowledge in the field, summarizing in a systematic way the major findings of research on ageing in several organs and tissues (crime scenes) expressing βARs: heart, vessels, skeletal muscle, respiratory system, brain, immune system, pancreatic islets, liver, kidney and bone.