| Title | Implications of maraviroc and/or rapamycin in a mouse model of fragility |
|---|---|
| Authors | Perez-Martinez, Laura , Romero, Lourdes , Munoz-Galvan, Sandra , VERDUGO SIVIANES, EVA MARÍA, Rubio-Mediavilla, Susana , Oteo, Jose A. , Carnero, Amancio , Blanco, Jose-Ramon |
| External publication | No |
| Means | Aging-US |
| Scope | Article |
| Nature | Científica |
| JCR Quartile | 1 |
| SJR Quartile | 2 |
| JCR Impact | 5.682 |
| SJR Impact | 1.473 |
| Publication date | 15/05/2020 |
| ISI | 000533150800059 |
| DOI | 10.18632/aging.103167 |
| 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-10(tm/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.\n 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.\n Conclusions: MVC and RAPA show a protective role in some factors involved in frailty. More studies are needed to prove their clinical applications.\n 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. |
| Keywords | CCR5 antagonist; frailty; myostatin; rapamycin |
| Universidad Loyola members |