Caloric restriction mimetic (CR mimetic)

A caloric restriction mimetic (CR mimetic) is a compound that reproduces some molecular and physiological effects of caloric restriction — including AMPK activation, mTORC1 inhibition, sirtuin activation, reduced insulin/IGF-1 signalling, enhanced autophagy and favourable shifts in metabolic biomarkers — without requiring a sustained reduction in food intake. The concept was formalised by Ingram and colleagues in 1998. Leading candidates include rapamycin (mTOR inhibitor), metformin (AMPK activator), resveratrol (putative SIRT1 activator), NAD+ precursors (NMN, NR) and acarbose. Evidence for lifespan extension in mice is established for rapamycin and acarbose under ITP conditions; translation to humans remains an open research question, and no CR mimetic has demonstrated robust healthspan extension in a powered randomised human trial.