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Concepts & theories

Caloric restriction mimetic (CR mimetic)

DEKalorische-Restriktions-Mimetikum (CR-Mimetikum)

A caloric restriction mimetic (CR mimetic) copies some effects of eating less, without you having to cut calories long-term. What effects? It activates AMPK and sirtuins. It inhibits mTORC1. It lowers insulin and IGF-1 signaling. It boosts autophagy. And it improves your metabolic markers. Ingram and colleagues formalized the concept in 1998. The leading candidates are well known. Rapamycin is an mTOR inhibitor. Metformin is an AMPK activator. Resveratrol is a proposed SIRT1 activator. And NAD+ precursors (NMN, NR) and acarbose round out the list. In mice, lifespan extension is established for rapamycin and acarbose, under a rigorous testing program (the ITP). Translating that to humans is still an open question. No CR mimetic has shown clear healthspan extension in a well-powered human trial.

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Sources

  1. Lane MA, Ingram DK, Roth GS. (1998). 2-deoxy-D-glucose feeding in rats mimics physiologic effects of calorie restriction. Journal of Anti-Aging Medicine
  2. Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS, deCabo R. (2006). Calorie restriction mimetics: an emerging research field. Aging Celldoi:10.1111/j.1474-9726.2006.00202.x
  3. Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. (2019). Caloric restriction mimetics against age-associated disease: targets, mechanisms, and therapeutic potential. Cell Metabolismdoi:10.1016/j.cmet.2019.01.018