Our findings indicate that RAPA reduced glucose uptake in the bladder and the percentage of FoxP3+ lymphocytes in the spleen of SAMP8 mice, while enhancing mitochondrial respiratory control and ATP production in skeletal muscle.
In SAMR1 mice, RAPA administration led to a decrease in CD3+ thymocytes and splenic lymphoproliferative capacity, while also enhanced mitochondrial performance. Comparisons between Control groups revealed that SAMP8 mice exhibited higher glucose uptake in several tissues, lower lymphocyte populations in spleen and thymus, altered CD4+/CD8+ ratios, and reduced IL-4 expression compared with SAMR1 mice.
The findings reinforce the potential of RAPA to modulate aging-related processes, highlighting improvements in mitochondrial function and energy metabolism across strains with different aging processes. However, the immunosuppressive effects of RAPA remain evident, even at low doses administered intermittently, in an age- and strain-specific manner.
These findings emphasize the therapeutic potential of RAPA while underscoring the need for customized dosing strategies to balance efficacy and safety. These data highlight mitochondrial metabolic improvements as the primary benefit of intermittent low-dose RAPA and suggest potential clinical relevance for conditions involving compromised mitochondrial energy metabolism.
Open access paper: