Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice

Clara Correia-Melo, Jodie Birch, Edward Fielder, Dina Rahmatika, Jennifer Taylor, James Chapman, Anthony Lagnado, Bernadette M. Carroll, Satomi Miwa, Gavin Richardson, Diana Jurk, Fiona Oakley, Jelena Mann, Derek A. Mann, Viktor I. Korolchuk, Joao Passos

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Increased activation of the major pro-inflammatory NF-κB 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-κB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF-κB 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-κB activity (nfκb1 −/− ) 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-κB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.

Original languageEnglish (US)
Article numbere12882
JournalAging Cell
Volume18
Issue number1
DOIs
StatePublished - Feb 1 2019

Fingerprint

Sirolimus
Chronic Disease
Liver Diseases
Inflammation
Phenotype
Long-Term Memory
Cell Aging
Pathology

Keywords

  • aging
  • inflammaging
  • mTOR
  • rapamycin
  • SASP
  • senescence

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Correia-Melo, C., Birch, J., Fielder, E., Rahmatika, D., Taylor, J., Chapman, J., ... Passos, J. (2019). Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice Aging Cell, 18(1), [e12882]. https://doi.org/10.1111/acel.12882

Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice . / Correia-Melo, Clara; Birch, Jodie; Fielder, Edward; Rahmatika, Dina; Taylor, Jennifer; Chapman, James; Lagnado, Anthony; Carroll, Bernadette M.; Miwa, Satomi; Richardson, Gavin; Jurk, Diana; Oakley, Fiona; Mann, Jelena; Mann, Derek A.; Korolchuk, Viktor I.; Passos, Joao.

In: Aging Cell, Vol. 18, No. 1, e12882, 01.02.2019.

Research output: Contribution to journalArticle

Correia-Melo, C, Birch, J, Fielder, E, Rahmatika, D, Taylor, J, Chapman, J, Lagnado, A, Carroll, BM, Miwa, S, Richardson, G, Jurk, D, Oakley, F, Mann, J, Mann, DA, Korolchuk, VI & Passos, J 2019, ' Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice ', Aging Cell, vol. 18, no. 1, e12882. https://doi.org/10.1111/acel.12882
Correia-Melo C, Birch J, Fielder E, Rahmatika D, Taylor J, Chapman J et al. Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice Aging Cell. 2019 Feb 1;18(1). e12882. https://doi.org/10.1111/acel.12882
Correia-Melo, Clara ; Birch, Jodie ; Fielder, Edward ; Rahmatika, Dina ; Taylor, Jennifer ; Chapman, James ; Lagnado, Anthony ; Carroll, Bernadette M. ; Miwa, Satomi ; Richardson, Gavin ; Jurk, Diana ; Oakley, Fiona ; Mann, Jelena ; Mann, Derek A. ; Korolchuk, Viktor I. ; Passos, Joao. / Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice In: Aging Cell. 2019 ; Vol. 18, No. 1.
@article{1251fc06793a4b918aa6727a3629103d,
title = "Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice",
abstract = "Increased activation of the major pro-inflammatory NF-κB 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-κB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF-κB 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-κB activity (nfκb1 −/− ) 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-κB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.",
keywords = "aging, inflammaging, mTOR, rapamycin, SASP, senescence",
author = "Clara Correia-Melo and Jodie Birch and Edward Fielder and Dina Rahmatika and Jennifer Taylor and James Chapman and Anthony Lagnado and Carroll, {Bernadette M.} and Satomi Miwa and Gavin Richardson and Diana Jurk and Fiona Oakley and Jelena Mann and Mann, {Derek A.} and Korolchuk, {Viktor I.} and Joao Passos",
year = "2019",
month = "2",
day = "1",
doi = "10.1111/acel.12882",
language = "English (US)",
volume = "18",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Rapamycin improves healthspan but not inflammaging in nfκb1 −/− mice

AU - Correia-Melo, Clara

AU - Birch, Jodie

AU - Fielder, Edward

AU - Rahmatika, Dina

AU - Taylor, Jennifer

AU - Chapman, James

AU - Lagnado, Anthony

AU - Carroll, Bernadette M.

AU - Miwa, Satomi

AU - Richardson, Gavin

AU - Jurk, Diana

AU - Oakley, Fiona

AU - Mann, Jelena

AU - Mann, Derek A.

AU - Korolchuk, Viktor I.

AU - Passos, Joao

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Increased activation of the major pro-inflammatory NF-κB 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-κB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF-κB 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-κB activity (nfκb1 −/− ) 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-κB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.

AB - Increased activation of the major pro-inflammatory NF-κB 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-κB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF-κB 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-κB activity (nfκb1 −/− ) 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-κB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.

KW - aging

KW - inflammaging

KW - mTOR

KW - rapamycin

KW - SASP

KW - senescence

UR - http://www.scopus.com/inward/record.url?scp=85060809804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060809804&partnerID=8YFLogxK

U2 - 10.1111/acel.12882

DO - 10.1111/acel.12882

M3 - Article

C2 - 30468013

AN - SCOPUS:85060809804

VL - 18

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

IS - 1

M1 - e12882

ER -