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Research Paper|Volume 12, Issue 9|pp 8565—8582

Implications of maraviroc and/or rapamycin in a mouse model of fragility

Laura Pérez-Martínez1, Lourdes Romero1, Sandra Muñoz-Galván2,3, Eva M. Verdugo-Sivianes2,3, Susana Rubio-Mediavilla4, José A. Oteo1,5, Amancio Carnero2,3, José-Ramón Blanco1,5
  • 1Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, España
  • 2Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Sevilla, España
  • 3CIBERONC, Instituto de Salud Carlos III, Madrid, España
  • 4Servicio de Anatomía Patológica, Hospital San Pedro, Logroño, España
  • 5Servicio de Enfermedades Infecciosas, Hospital San Pedro, Logroño, España
Received: January 29, 2020Accepted: March 31, 2020Published: April 30, 2020
https://doi.org/10.18632/aging.103167

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.