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.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Pérez-Martínez L,Romero L,Muñoz-Galván S,Verdugo-Sivianes EM,Rubio-Mediavilla S,Oteo JA,Carnero A,Blanco JRdoi
10.18632/aging.103167subject
Has Abstractpub_date
2020-04-30 00:00:00pages
8565-8582issue
9issn
1945-4589pii
103167journal_volume
12pub_type
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