Caloric restriction mimetic

Calorie restriction mimetics (CRM), also known as Energy restriction mimetics, designate a hypothetical class of dietary supplement or drug candidate that would in principle mimic the substantial anti-aging effects that calorie restriction (CR) has on many laboratory animals. CR is defined as a reduction in calorie intake of 20% (mild CR) to 50% (severe CR) without incurring malnutrition or a reduction in essential nutrients.[1] The benefits of CR can be interpreted as arising from the mild stress induced in an organism, which activate endogenous compensating mechanisms that improve the overall protection against stress. Such compensations include enhanced expression of heat shock proteins and antioxidant enzymes. An effective CRM would alter the key metabolic pathways involved in the effects of CR itself, leading to preserved youthful health and longer lifespan without the need to reduce food intake. The term was coined by Lane, Ingram, Roth of the National Institute on Aging in a seminal 1998 paper in the Journal of Anti-Aging Medicine, the forerunner of Rejuvenation Research.[2] A number of genes and pathways have been shown to be involved the actions of CR in model organisms and these represent attractive targets for drug discovery and for developing CRM. However, no effective CRM have been identified to date.[1][3][4]

Candidate compounds include:

Because of its parallel effects on these pathways, oxaloacetate was proposed as a CR mimetic.[16] In the short-lived roundworm Caenorhabditis elegans, supplementing the medium with oxaloacetate does increase average life expectancy; it was unclear whether it had an effect on maximum lifespan.[16][19] However, when tested by two independent groups of scientists across four university laboratories, oxaloacetate supplements had no effect on lifespan in healthy laboratory mice.[10][20]

Other candidate CRM are:

References

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  2. 1 2 3 Lane MA; Ingram DK; Roth GS (Winter 1998). "2-Deoxy-D-glucose feeding in rats mimics physiologic effects of calorie restriction". J Anti-Aging Med 1 (4): 327–37. doi:10.1089/rej.1.1998.1.327. Retrieved 1 October 2013.
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