Cargando…

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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: Leysen, Hanne, Walter, Deborah, Clauwaert, Lore, Hellemans, Lieselot, van Gastel, Jaana, Vasudevan, Lakshmi, Martin, Bronwen, Maudsley, Stuart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027355/
https://www.ncbi.nlm.nih.gov/pubmed/35457203
http://dx.doi.org/10.3390/ijms23084387
_version_ 1784691342232780800
author Leysen, Hanne
Walter, Deborah
Clauwaert, Lore
Hellemans, Lieselot
van Gastel, Jaana
Vasudevan, Lakshmi
Martin, Bronwen
Maudsley, Stuart
author_facet Leysen, Hanne
Walter, Deborah
Clauwaert, Lore
Hellemans, Lieselot
van Gastel, Jaana
Vasudevan, Lakshmi
Martin, Bronwen
Maudsley, Stuart
author_sort Leysen, Hanne
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9027355
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90273552022-04-23 The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease Leysen, Hanne Walter, Deborah Clauwaert, Lore Hellemans, Lieselot van Gastel, Jaana Vasudevan, Lakshmi Martin, Bronwen Maudsley, Stuart Int J Mol Sci Review 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. MDPI 2022-04-15 /pmc/articles/PMC9027355/ /pubmed/35457203 http://dx.doi.org/10.3390/ijms23084387 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Leysen, Hanne
Walter, Deborah
Clauwaert, Lore
Hellemans, Lieselot
van Gastel, Jaana
Vasudevan, Lakshmi
Martin, Bronwen
Maudsley, Stuart
The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
title The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
title_full The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
title_fullStr The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
title_full_unstemmed The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
title_short The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
title_sort relaxin-3 receptor, rxfp3, is a modulator of aging-related disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027355/
https://www.ncbi.nlm.nih.gov/pubmed/35457203
http://dx.doi.org/10.3390/ijms23084387
work_keys_str_mv AT leysenhanne therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT walterdeborah therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT clauwaertlore therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT hellemanslieselot therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT vangasteljaana therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT vasudevanlakshmi therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT martinbronwen therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT maudsleystuart therelaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT leysenhanne relaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT walterdeborah relaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT clauwaertlore relaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT hellemanslieselot relaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT vangasteljaana relaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT vasudevanlakshmi relaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT martinbronwen relaxin3receptorrxfp3isamodulatorofagingrelateddisease
AT maudsleystuart relaxin3receptorrxfp3isamodulatorofagingrelateddisease