Research Paper Volume 12, Issue 9 pp 8565—8582
Implications of maraviroc and/or rapamycin in a mouse model of fragility
- 1 Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, España
- 2 Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Sevilla, España
- 3 CIBERONC, Instituto de Salud Carlos III, Madrid, España
- 4 Servicio de Anatomía Patológica, Hospital San Pedro, Logroño, España
- 5 Servicio de Enfermedades Infecciosas, Hospital San Pedro, Logroño, España
Received: January 29, 2020 Accepted: March 31, 2020 Published: April 30, 2020
https://doi.org/10.18632/aging.103167How to Cite
Copyright © 2020 Pérez-Martínez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: As age increases, the risk of developing fragility also increases. Improving the knowledge of frailty could contribute to maintaining the functional ability of elderly people. Interleukin (IL)-10 homozygous knockout mice (IL-10tm/tm [IL10KO]) constitute an excellent tool for the study of frailty. Because patients with frailty demonstrate an overexpression of CCR5, rapamycin (RAPA) and/or maraviroc (MVC), two molecules able to decrease CCR5 expression, were evaluated.
Results: Muscle myostatin was reduced in all the therapeutic groups but the MVC group (p <0.001 for RAPA and MVC-RAPA) and in serum samples (p <0.01 for all the groups). Serum CK levels were also significantly lower in MVC and RAPA groups (p <0.01 in both cases). Lower AST levels were observed in all the therapeutic groups (p <0.05 for all of them). The apoptotic effector caspase-3 was significantly lower in MVC and RAPA groups (p<0.05 in both cases). Combined treatment with MVC-RAPA showed a synergistic increase in p-AKT, p-mTOR and SIRT1 levels.
Conclusions: MVC and RAPA show a protective role in some factors involved in frailty. More studies are needed to prove their clinical applications.
Material and methods: Eighty male homozygous IL10KOs were randomly assigned to one of 4 groups (n= 20): i) IL10KO group (IL10KO); ii) IL10KO receiving MVC in drinking water (MVC group), iii) IL10KO receiving RAPA in drinking water (RAPA group), and finally, iv) MVC-RAPA group that received MVC and RAPA in drinking water. Blood and muscle samples were analysed. Survival analysis, frailty index calculation, and functional assessment were also performed.