The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease

During the aging process our body becomes less well equipped to deal with cellular stress, resulting in an increase in unrepaired damage. This causes varying degrees of impaired functionality and an increased risk of mortality. One of the most effective anti-aging strategies involves interventions that combine simultaneous glucometabolic support with augmented DNA damage protection/repair. Thus, it seems prudent to develop therapeutic strategies that target this combinatorial approach. Studies have shown that the ADP-ribosylation factor (ARF) GTPase activating protein GIT2 (GIT2) acts as a keystone protein in the aging process. GIT2 can control both DNA repair and glucose metabolism. Through in vivo co-regulation analyses it was found that GIT2 forms a close coexpression-based relationship with the relaxin-3 receptor (RXFP3). Cellular RXFP3 expression is directly affected by DNA damage and oxidative stress. Overexpression or stimulation of this receptor, by its endogenous ligand relaxin 3 (RLN3), can regulate the DNA damage response and repair processes. Interestingly, RLN3 is an insulin-like peptide and has been shown to control multiple disease processes linked to aging mechanisms, e.g., anxiety, depression, memory dysfunction, appetite, and anti-apoptotic mechanisms. Here we discuss the molecular mechanisms underlying the various roles of RXFP3/RLN3 signaling in aging and age-related disorders.

Automated summary

During aging, the body becomes less capable of dealing with cellular stress and repairing damage, leading to impaired functionality and increased mortality risk. Combining interventions that support glucose metabolism and protect/repair DNA damage has been shown to be an effective anti-aging strategy. The ARF GTPase activating protein GIT2 plays a key role in the aging process by controlling both DNA repair and glucose metabolism. The relaxin-3 receptor RXFP3 forms a close relationship with GIT2 and is directly affected by DNA damage and oxidative stress. Stimulating the RXFP3/RLN3 signaling pathway can regulate the DNA damage response and repair processes, providing a significant impact on aging and age-related disorders.