Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice.
aging
branched-chain amino acids
frailty
isoleucine
lifespan
metabolic health
mice
nutritional interventions
protein restriction
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
07 11 2023
07 11 2023
Historique:
received:
30
05
2023
revised:
01
09
2023
accepted:
11
10
2023
pmc-release:
07
11
2024
medline:
10
11
2023
pubmed:
9
11
2023
entrez:
8
11
2023
Statut:
ppublish
Résumé
Low-protein diets promote health and longevity in diverse species. Restriction of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine recapitulates many of these benefits in young C57BL/6J mice. Restriction of dietary isoleucine (IleR) is sufficient to promote metabolic health and is required for many benefits of a low-protein diet in C57BL/6J males. Here, we test the hypothesis that IleR will promote healthy aging in genetically heterogeneous adult UM-HET3 mice. We find that IleR improves metabolic health in young and old HET3 mice, promoting leanness and glycemic control in both sexes, and reprograms hepatic metabolism in a sex-specific manner. IleR reduces frailty and extends the lifespan of male and female mice, but to a greater degree in males. Our results demonstrate that IleR increases healthspan and longevity in genetically diverse mice and suggests that IleR, or pharmaceuticals that mimic this effect, may have potential as a geroprotective intervention.
Identifiants
pubmed: 37939658
pii: S1550-4131(23)00374-1
doi: 10.1016/j.cmet.2023.10.005
pmc: PMC10655617
mid: NIHMS1939504
pii:
doi:
Substances chimiques
Isoleucine
04Y7590D77
Amino Acids, Branched-Chain
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1976-1995.e6Subventions
Organisme : NIA NIH HHS
ID : R56 AG056771
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG066311
Pays : United States
Organisme : BLRD VA
ID : I01 BX004031
Pays : United States
Organisme : NIDCR NIH HHS
ID : P50 DE026787
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG082504
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG084156
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062328
Pays : United States
Organisme : NIA NIH HHS
ID : F32 AG077916
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA029124
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG000213
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG056771
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020579
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056771
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG081115
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK133479
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125859
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD101368
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK131175
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG059899
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG081482
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK104310
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.W.L. has received funding from, and is a scientific advisory board member of, Aeovian Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases.
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