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Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11913-11918. Epub 2016 Oct 3.

Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK.

Author information

1
Hiroshima Research Center for Healthy Aging, Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8530, Japan.
2
National Research Institute of Brewing, Higashi-Hiroshima, Hiroshima 739-0046, Japan.
3
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
4
Hiroshima Research Center for Healthy Aging, Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8530, Japan; mmizu49120@hiroshima-u.ac.jp.

Abstract

Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulating S-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeast Saccharomyces cerevisiae The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed, stimulating AdoMet synthesis activated the universal energy-sensing regulator Snf1, which is the S. cerevisiae ortholog of AMP-activated protein kinase (AMPK), resulting in lifespan extension. Furthermore, our findings revealed that S-adenosyl-l-homocysteine contributed to longevity with a higher accumulation of AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data uncovered molecular links between Met metabolites and lifespan, suggesting a unique function of AdoMet as a reservoir of Met and ATP for cell survival.

KEYWORDS:

AMP-activated protein kinase; S-adenosyl-l-homocysteine; S-adenosyl-l-methionine; calorie restriction; yeast

PMID:
27698120
PMCID:
PMC5081624
DOI:
10.1073/pnas.1604047113
[Indexed for MEDLINE]
Free PMC Article

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