期刊
AGING CELL
卷 18, 期 1, 页码 -出版社
WILEY
DOI: 10.1111/acel.12882
关键词
aging; inflammaging; mTOR; rapamycin; SASP; senescence
资金
- Biotechnology and Biological Sciences Research Council [BB/H022384/1, BB/K017314/1]
- British Heart Foundation [PG/15/85/31744]
- Medical Research Council (MRC) [MR/K001949/1]
- Cancer Research UK [C18342/A2390]
- BBSRC [BB/J007803/1, BB/K017314/1, BB/M023389/1, BB/H022384/1] Funding Source: UKRI
- MRC [G0900535, MR/R023026/1, MR/L016354/1, MR/K001949/1] Funding Source: UKRI
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 (nfb1(-/-)) 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.
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