Is Rapamycin a Dietary Restriction Mimetic?
Dietary restriction
Insulin sensitivity
Lifespan
Rapamycin
TOR
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
12
09
2018
accepted:
28
02
2019
pubmed:
12
3
2019
medline:
13
8
2020
entrez:
12
3
2019
Statut:
ppublish
Résumé
Since the initial suggestion that rapamycin, an inhibitor of target of rapamycin (TOR) nutrient signaling, increased lifespan comparable to dietary restriction, investigators have viewed rapamycin as a potential dietary restriction mimetic. Both dietary restriction and rapamycin increase lifespan across a wide range of evolutionarily diverse species (including yeast, Caenorhabditis elegans, Drosophila, and mice) as well as reducing pathology and improving physiological functions that decline with age in mice. The purpose of this article is to review the research comparing the effect of dietary restriction and rapamycin in mice. The current data show that dietary restriction and rapamycin have different effects on many pathways and molecular processes. In addition, these interventions affect the lifespan of many genetically manipulated mouse models differently. In other words, while dietary restriction and rapamycin may have similar effects on some pathways and processes; overall, they affect many pathways/processes quite differently. Therefore, rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone.
Identifiants
pubmed: 30854544
pii: 5373089
doi: 10.1093/gerona/glz060
pmc: PMC6909904
doi:
Substances chimiques
TOR Serine-Threonine Kinases
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4-13Subventions
Organisme : NIA NIH HHS
ID : R01 AG057431
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG050911
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013319
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG050797
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG044271
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG056655
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG045693
Pays : United States
Organisme : BLRD VA
ID : IK6 BX005238
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America.
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