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Growth Hormone Guidance

Intact growth hormone signaling pathways are needed for methionine restriction to extend
mouse lifespan.
By Jenny Rood | March 1, 2015

OLD MICE: Ames dwarf mice (above, right)


outlive wild-type mice (above, left), but their life span is unresponsive to changes in dietary
methionine levels.CHUCK KIMMERLE AT UNIVERSITY OF NORTH DAKOTA

EDITOR'S CHOICE IN MOLECULAR BIOLOGY


The Paper
H.M. Brown-Borg et al., Growth hormone signaling is necessary for lifespan extension by
dietary methionine, Aging Cell, 13:1019-27, 2014.
The paradox
Genetic defects in growth-hormone (GH) signaling extend life span in mice, as do diets
minimizing the intake of a single amino acid, methionine. Yet scientists had previously
observed that the Ames dwarf mouse, deficient in GH, lives longer but has upregulated
methionine metabolism. Holly Brown-Borg of the University of North Dakota and her
colleagues thus decided to examine how GH genetics and dietary methionine might interact
to impact life span.
The diet
Brown-Borgs team compared four groups of mice on three different diets. Ames dwarf mice,
GH-receptor knockout mice, transgenic mice that overexpressed GH, and wild-type controls
were fed a diet with an 80 percent reduction, a 50 percent reduction, or a 50 percent increase
in typical methionine levels. Methionine restriction extended the life span of the GH
transgenic mice and the wild-type controls, but did not impact the life span of the Ames
dwarf or GH receptor knockout mice.
The resistance
Animals that dont have growth-hormone signaling are unable to respond to the drop in
dietary methionine, says Brown-Borg. Follow- up studies by her group indicate that the
altered metabolism of these GH-deficient mice is indifferent to changes in methionine intake.

They really dont discriminate either metabolically or in terms of life span when compared
to other animals, she says.
The mechanism
Matt Kaeberlein of the University of Washington praises the paper as a really nice example
of a rare study investigating the interaction of genes and environment in aging, and hopes for
a future mechanistic explanation. Brown-Borg speculates that the link might be epigenetic,
given DNA-methylating enzymes requirement for methionine.