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

Takafumi Ogawa, Ryohei Tsubakiyama, Muneyoshi Kanai, Tetsuya Koyama, Tsutomu Fujii, Haruyuki Iefuji, Tomoyoshi Soga, Kazunori Kume, Tokichi Miyakawa, Dai Hirata, Masaki Mizunuma

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11913-11918
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number42
DOIs
Publication statusPublished - 2016 Oct 18

Fingerprint

S-Adenosylmethionine
AMP-Activated Protein Kinases
Methionine
Saccharomyces cerevisiae
Adenosine Triphosphate
Saccharomycetales
Homocysteine
Cell Survival
Glucose

Keywords

  • AMP-activated protein kinase
  • Calorie restriction
  • S-adenosyl-L-homocysteine
  • S-adenosyl-L-methionine
  • Yeast

ASJC Scopus subject areas

  • General

Cite this

Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK. / Ogawa, Takafumi; Tsubakiyama, Ryohei; Kanai, Muneyoshi; Koyama, Tetsuya; Fujii, Tsutomu; Iefuji, Haruyuki; Soga, Tomoyoshi; Kume, Kazunori; Miyakawa, Tokichi; Hirata, Dai; Mizunuma, Masaki.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 42, 18.10.2016, p. 11913-11918.

Research output: Contribution to journalArticle

Ogawa, T, Tsubakiyama, R, Kanai, M, Koyama, T, Fujii, T, Iefuji, H, Soga, T, Kume, K, Miyakawa, T, Hirata, D & Mizunuma, M 2016, 'Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 42, pp. 11913-11918. https://doi.org/10.1073/pnas.1604047113
Ogawa, Takafumi ; Tsubakiyama, Ryohei ; Kanai, Muneyoshi ; Koyama, Tetsuya ; Fujii, Tsutomu ; Iefuji, Haruyuki ; Soga, Tomoyoshi ; Kume, Kazunori ; Miyakawa, Tokichi ; Hirata, Dai ; Mizunuma, Masaki. / Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 42. pp. 11913-11918.
@article{87255657831f4d0d9c464f3b6660cf93,
title = "Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK",
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, Calorie restriction, S-adenosyl-L-homocysteine, S-adenosyl-L-methionine, Yeast",
author = "Takafumi Ogawa and Ryohei Tsubakiyama and Muneyoshi Kanai and Tetsuya Koyama and Tsutomu Fujii and Haruyuki Iefuji and Tomoyoshi Soga and Kazunori Kume and Tokichi Miyakawa and Dai Hirata and Masaki Mizunuma",
year = "2016",
month = "10",
day = "18",
doi = "10.1073/pnas.1604047113",
language = "English",
volume = "113",
pages = "11913--11918",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "42",

}

TY - JOUR

T1 - Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK

AU - Ogawa, Takafumi

AU - Tsubakiyama, Ryohei

AU - Kanai, Muneyoshi

AU - Koyama, Tetsuya

AU - Fujii, Tsutomu

AU - Iefuji, Haruyuki

AU - Soga, Tomoyoshi

AU - Kume, Kazunori

AU - Miyakawa, Tokichi

AU - Hirata, Dai

AU - Mizunuma, Masaki

PY - 2016/10/18

Y1 - 2016/10/18

N2 - 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.

AB - 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.

KW - AMP-activated protein kinase

KW - Calorie restriction

KW - S-adenosyl-L-homocysteine

KW - S-adenosyl-L-methionine

KW - Yeast

UR - http://www.scopus.com/inward/record.url?scp=84991712518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991712518&partnerID=8YFLogxK

U2 - 10.1073/pnas.1604047113

DO - 10.1073/pnas.1604047113

M3 - Article

C2 - 27698120

AN - SCOPUS:84991712518

VL - 113

SP - 11913

EP - 11918

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 42

ER -