S6K1 Inhibition Reduces Liver Inflammation, a Possible Mechanism Mediating Slowed Aging
Decreased expression of S6K1 is a consequence of mTOR inhibition, a method known to slow aging in animal studies. Researchers have found that inhibiting S6K1 reduces liver inflammation by decreasing senescent cells and their inflammatory secretions. This could be a key mechanism through which mTOR inhibition enhances overall health in later stages of life.
Inhibiting S6 kinase 1 (S6K1) has been shown to extend lifespan and improve healthspan in mice, but the mechanisms behind this are not fully understood. Cellular senescence along with its inflammatory profile (SASP) play a role in age-related diseases. In this study, it was discovered that deleting S6K1 does not reduce senescence but does alleviate inflammation in aging mouse livers. Both human and mouse models support the idea that reduced inflammation is a liver-specific effect of S6K deletion.
Specifically, the study shows that S6K1 deletion leads to decreased activation of IRF3, reduced cytokine production like IL1β, and less immune cell infiltration. By using mice with liver or myeloid cell-specific S6K knockout, it was revealed that reducing immune cell infiltration and clearing senescent cells is an intrinsic property of hepatocytes. Overall, S6K deletion decreases liver inflammation, suggesting that inhibiting this pathway may have beneficial effects on healthspan and lifespan by suppressing the inflammatory SASP output.
Link: https://doi.org/10.1038/s43587-024-00695-z
