Mittwoch, 15. Oktober 2014

Short Notes: Methionine-mediated lifespan extension solely dependent on GH signalling?

Aging Cell. 2014 Sep 19. doi: 10.1111/acel.12269.
[Epub ahead of print]Growth hormone signaling is necessary for lifespan extension by dietary methionine.
Brown-Borg HM1, Rakoczy SG, Wonderlich JA, Rojanathammanee L, Kopchick JJ, Armstrong V, Raasakka D.

...Methionine intake affects also lifespan, and thus, GH mutant mice and respective wild-type littermates were fed 0.16%, 0.43%, or 1.3% methionine to evaluate the interaction between hormone status and methionine. All wild-type and GH transgenic mice lived longer when fed 0.16% methionine but not when fed higher levels. In contrast, animals without growth hormone signaling due to hormone deficiency or resistance did not respond to altered levels of methionine in terms of lifespan, body weight, or food consumption. Taken together, our results suggest that the presence of growth hormone is necessary to sense dietary methionine changes, thus strongly linking growth and lifespan to amino acid availability.

Methodological note: some of the control mice in this paper are somewhat short-lived, especially dwarf control and some GHRKO controls.

This reminds me of the Bartke papers showing how difficult (almost impossible) it is to further extend the lifespan of GHRKO mice by restricting them. Taken together these papers have the obvious implication that most life extending interventions (CR, MR possibly essential AA restriction) act through suppressed GH signalling or converge on the same effectors.

Overall, this means that we should seek to find interventions that extend LS on top of CR/GHRKO, if we want to identify novel pathwys.

Methionine moderation
Met moderation has been proposed as a feasible strategy to promote health span and lifespan (e.g. by Michael Rae, or Richie JP). In contrast, methionine moderation (0.43%) had no effect whatsoever in this study.

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