Rapamycin improves healthspan but not inflammaging in nf?b1-/- mice.

ABSTRACT: Increased activation of the major pro-inflammatory NF-?B pathway leads to numerous age-related diseases, including chronic liver disease (CLD). Rapamycin, an inhibitor of mTOR, extends lifespan and healthspan, potentially via suppression of inflammaging, a process which is partially dependent on NF-?B signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF-?B signalling, such as that which occurs in several age-related chronic diseases. In this study, we investigated whether rapamycin could ameliorate age-associated phenotypes in a mouse model of genetically enhanced NF-?B activity (nf?b1-/- ) characterized by low-grade chronic inflammation, accelerated aging and CLD. We found that, despite showing no beneficial effects in lifespan and inflammaging, rapamycin reduced frailty and improved long-term memory, neuromuscular coordination and tissue architecture. Importantly, markers of cellular senescence, a known driver of age-related pathology, were alleviated in rapamycin-fed animals. Our results indicate that, in conditions of genetically enhanced NF-?B, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.

SUBMITTER: Correia-Melo C 

PROVIDER: S-EPMC6351839 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other