Calorie Restriction (CR) Mimetics
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What is a CR Mimetic?
A CR (Calorie Restriction) mimetic may -- if successful -- enable organisms to derive many of the health and life-extending benefits seen in calorie-restricted diets. This may, then, allow the organism to "eat normally" and enjoy a longevous lifespan. The efficacy of such compounds would, upon safe and successful testing in animal subjects, pave the way for substantial increases in human lifespan.
How does a CR Mimetic work?
Is there any molecular and/or empirical evidence? And what compounds have currently been identified as potential CR mimetics?
The Major Players:
1: Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5524-9. Epub 2004 Mar
25. Related Articles, Links
Dhahbi JM, Kim HJ, Mote PL, Beaver RJ, Spindler SR.
BioMarker Pharmaceuticals, Incorporated, 900 East Hamilton Avenue, Campbell, CA 95008, USA.
Caloric restriction (CR), the consumption of fewer calories while avoiding malnutrition, decelerates the rate of aging and the development of age-related diseases. CR has been viewed as less effective in older animals and as acting incrementally to slow or prevent age-related changes in gene expression. Here we demonstrate that CR initiated in 19-month-old mice begins within 2 months to increase the mean time to death by 42% and increase mean and maximum lifespans by 4.7 (P = 0.000017) and 6.0 months (P = 0.000056), respectively. The rate of age-associated mortality was decreased 3.1-fold. Between the first and second breakpoints in the CR survival curve (between 21 and 31 months of age), tumors as a cause of death decreased from 80% to 67% (P = 0.012). Genome-wide microarray analysis of hepatic RNA from old control mice switched to CR for 2, 4, and 8 weeks showed a rapid and progressive shift toward the gene expression profile produced by long-term CR. This shift took place in the time frame required to induce the health and longevity effects of CR. Shifting from long-term CR to a control diet, which returns animals to the control rate of aging, reversed 90% of the gene expression effects of long-term CR within 8 weeks. These results suggest a cause-and-effect relationship between the rate of aging and the CR-associated gene expression biomarkers. Therefore, therapeutics mimicking the gene-expression biomarkers of CR may reproduce its physiological effects.
PMID: 15044709 [PubMed - in process]
6: Calorie Restriction Mimetics By Marios Kyriazis.