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Autophagy. 2019 Mar;15(3):558-559. doi: 10.1080/15548627.2018.1533059. Epub 2018 Oct 18.

Methionine restriction for improving progeria: another autophagy-inducing anti-aging strategy?

Bárcena C1,2, López-Otín C1,2, Kroemer G3,4,5,6,7,8,9,10,11.

Author information

1
a Departamento de Bioquímica y Biología Molecular, Facultad de Medicina , Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo , Oviedo , Spain.
2
b Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) , Madrid , Spain.
3
c Gustave Roussy Cancer Campus , Villejuif , France.
4
d INSERM, U1138 , Paris , France.
5
e Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.
6
f Université Paris Descartes/Paris V, Sorbonne Paris Cité , Paris , France.
7
g Sorbonne Université , Paris , France.
8
h Université Paris-Sud/Paris XI, Faculté de Médecine , Kremlin-Bicêtre , France.
9
i Metabolomics and Cell Biology Platforms , Gustave Roussy Cancer Campus , Villejuif , France.
10
j Pôle de Biologie, Hôpital Européen Georges Pompidou , Karolinska Institute, AP-HP , Paris , France.
11
k Department of Women's and Children's Health , Karolinska University Hospital , Stockholm , Sweden.

Abstract

Methionine restriction, i.e., a partial depletion of the essential sulfur amino acid methionine from nutrition, extends lifespan in model organisms including yeast, nematodes, mice and rats. Recent results indicate that this strategy also prolongs health span and longevity in 2 short-lived strains of mice (with the LmnaG609G/G609G or zmpste24-/- genotypes) that represent animal models of Hutchinson-Gilford progeria syndrome (HGPS). The beneficial effects of methionine restriction on HGPS could be linked to reduced inflammation, and improved DNA stability, as well as the normalization of lipid and bile acid metabolism. Previous work has established that behavioral, nutritional, pharmacological and genetic manipulations that extend longevity in model organisms are only efficient if they induce increased autophagic flux. Methionine restriction extends lifespan in Saccharomyces cerevisiae in an Atg5- and Atg7-dependent fashion, supporting the notion that methionine restriction may indeed mediate its antiaging effects through the induction of macroautophagy/autophagy as well. Based on these findings, we speculate that autophagy might constitute an actionable therapeutic target to treat progeroid syndromes.

KEYWORDS:

Caloric restriction; DNA damage response; cholic acid; inflammation; lipid metabolism

PMID:
30304972
PMCID:
PMC6351129
[Available on 2019-10-18]
DOI:
10.1080/15548627.2018.1533059

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