cron-web.org

[A1CR]

A CRONie posted this study [1] which I found most interesting in light of
the data collected on some of us human CRONies as part of a human CR study
at U. of Washington at St. Louis (WUSTL).

Study [1] found that the cellular "house cleaning" process call autophagy
is:

* potentially important for longevity

* upregulated by CR

* increased in conditions of low plasma amino acids

* increased in conditions of low insulin concentrations

I found it very encouraging that virtually all the CRONies tested
at WUSTL had fairly low plasma amino acid and insulin levels. More evidence
that CRON is having the same metabolic effects in humans as it does in other
organisms - lending credence to the idea that CRON will increase longevity in
people as it does in animals.

-Dean

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[1] Mechanisms of Ageing and Development, In Press, Corrected Proof, Available online 21 January 2004

Autophagy and aging importance of amino acid levels,

Wulf Drvge

Melendez et al. [Science 301 (2003) 1387] have recently shown that the increased longevity of Caenorhabditis elegans mutants with defective Daf-2 protein, i.e. an insulin receptor analog, involves increased autophagy.
Autophagy increases the free amino acid pool and is in certain cells essential for survival at times of limited amino acid availability. In addition, autophagy plays an important role in the turnover of proteins and organelles including mitochondria. The autophagic activity is sensitive to changes in physiological conditions, i.e. it is strongly inhibited by an increase in amino acid concentrations or in insulin receptor signaling. In line with this fact, clinical studies indicate that autophagy mainly occurs at times of low plasma amino acid and insulin concentrations in the post-absorptive (fasted) state, and that the post-absorptive amino acid-sensitive protein catabolism may be taken as a bona fide indicator of autophagic activity. The increased longevity of insulin
receptor mutants or of organisms subjected to calorie restriction may, therefore, be attributed to an increase in autophagic activity. Importantly, the autophagic activity decreases with age. Recent studies suggest that this decrease may result from an age-related increase in post-absorptive amino acid levels and/or from an increase in baseline insulin receptor signaling.
If so, it is potentially reversible.