| First Author | Correia-Melo C | Year | 2019 |
| Journal | Aging Cell | Volume | 18 |
| Issue | 1 | Pages | e12882 |
| PubMed ID | 30468013 | Mgi Jnum | J:273021 |
| Mgi Id | MGI:6275663 | Doi | 10.1111/acel.12882 |
| Citation | Correia-Melo C, et al. (2019) Rapamycin improves healthspan but not inflammaging in nfkappab1(-/-) mice. Aging Cell 18(1):e12882 |
| abstractText | Increased activation of the major pro-inflammatory NF-kappaB 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-kappaB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF-kappaB 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-kappaB activity (nfkappab1(-/-) ) 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-kappaB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation. |
