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[A1CR]

80% reduction in calories for 4 days...changes characterized......

[posted on behalf of CRON4healthyfuture]

I am not going to say that this is "safe" or "suggested", but what I would say is that this study is an impressively rigorous analysis of most of the known contributors to cellular anabolism.

In other words, this type of study is a realization of the promise of signal transduction. It represents the "future" of biology.

Some of these signaling elements already feature very prominently in all types of "longevity research". My own personal take is that this is exactly what you are "tuning down". Not turning off, but "tuning down", in CR.

This study is probably closer to "turning off", but, I still find it very representative of the type of analysis I want to see personally.

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Effect of Severe Short-term Malnutrition on Diaphragm Muscle Signal Transduction Pathways Influencing Protein Turnover
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"The aim of this study was to evaluate the effect of nutritional deprivation (ND) on signal transduction pathways impinging on the translational apparatus in the diaphragm muscle. Male rats were divided into 2 groups: 1) ND (20% of usual food intake) for 4 days with water provided at libitum; and 2) free-eating controls (CTL). Total protein and RNA were extracted from the diaphragm. IGF-I mRNA was analyzed by RT-PCR. Protein analyses of key cytoplasmic proteins for 3 signaling pathways deemed important in influencing protein turnover were performed by Western blot. Body weight was reduced 30% with ND while CTL gained 17%. Diaphragm mass decreased by 29% with ND. Muscle IGF-I mRNA abundance was reduced by 63% in ND animals. PI3 kinase/Akt/mTOR pathway: ND resulted in a 55% reduction in phosphorylated (Ser473) Akt. The phosphorylation of mTOR at Ser2448 was reduced by 85% with ND. Downstream effectors important in translation initiation were also impacted by ND. Phosphorylate
d
(Thr389) p70S6K was significantly reduced (35%) with ND. The translational repressor 4E-BP1 was also significantly dephosphorylated with ND. PI3 kinase/Akt/Glycogen Synthase Kinase (GSK)-3 pathway: The phosphorylation (Ser21/9) of both GSK-3/ was increased (55/45%) with ND. MAP kinase/ERK pathway: The phosphorylation (Thr202/Tyr204) of both ERK1/2 (p44/p42) was reduced (64/55%) with ND. The concentrations of total protein for all signaling intermediates of the 3 pathways were preserved. We conclude that short-term ND altered the phosphorylation states of key proteins of several pathways involved in protein turnover. This forms the framework for future studies aimed at identifying therapeutic targets in the management of short-term nutritionally induced cachectic states."

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http://jap.physiology.org/cgi/content/abstract/01233.2005v1