Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status.
Reduced methionine (Met) intake can extend lifespan of rodents; however, whether this regimen represents a general strategy for regulating aging has been controversial. Here we report that Met restriction extends lifespan in both fruit flies and yeast, and that this effect requires low amino-acid status. Met restriction in Drosophila mimicks the effect of dietary restriction and is associated with decreased reproduction. However, under conditions of high amino-acid status, Met restriction is ineffective and the trade-off between longevity and reproduction is not observed. Overexpression of InRDN or Tsc2 inhibits lifespan extension by Met restriction, suggesting the role of TOR signalling in the Met control of longevity. Overall, this study defines the specific roles of Met and amino-acid imbalance in aging and suggests that Met restiction is a general strategy for lifespan extension.
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Byung Cheon
BC
Lee
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Alaattin
A
Kaya
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Siming
S
Ma
Department of Statistics, Korea University, Seoul 136-701, South Korea.
Gwansu
G
Kim
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Maxim V
MV
Gerashchenko
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Sun Hee
SH
Yim
School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, USA.
Zhen
Z
Hu
School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, USA.
Lawrence G
LG
Harshman
Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Vadim N
VN
Gladyshev
D000375:Aging / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D018797:Cell Cycle Proteins / Q000378:metabolism; D004044:Dietary Proteins; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005247:Feeding Behavior; D005260:Female; D008136:Longevity; D008297:Male; D008715:Methionine / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012098:Reproduction; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000596:Amino Acids; D018797:Cell Cycle Proteins; D004044:Dietary Proteins; D029721:Drosophila Proteins; C117726:gig protein, Drosophila; D008715:Methionine; C416303:target of rapamycin protein, Drosophila; C094982:InR protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases