Calorie restriction mimetics: can you have your cake and eat it, too?

摘要: Strong consensus exists regarding the most robust environmental intervention for attenuating aging processes and increasing healthspan lifespan: calorie restriction (CR). Over several decades, this paradigm has been replicated in numerous nonhuman models, expanded over last decade to formal, controlled human studies of CR. Given that long-term CR can create heavy challenges compliance diets, concept a mimetic (CRM) emerged as an active research area within gerontology. In past presentations on subject, we have proposed CRM is compound mimics metabolic, hormonal, physiological effects CR, activates stress response pathways observed enhances protection, produces CR-like longevity, reduces age-related disease, maintains more youthful function, all without significantly reducing food intake, at least initially. 16 years ago, glycolytic inhibition could be effective strategy developing CRM. The main argument here inhibiting energy utilization far upstream possible provides highest chance generating broad spectrum when compared targeting singular molecular target downstream. As initial candidate CRM, 2-deoxyglucose, known anti-glycolytic, was shown produce remarkable phenotype but further investigation found produced cardiotoxicity rats doses had using. There remains interest 2DG lower doses. Beyond proposal field grown steadily with many investigators proposing other strategies, including novel anti-glycolytics. Within realm level digestive system, included bariatric surgery, inhibitors fat digestion/absorption, carbohydrate digestion. Research focused downstream sites insulin receptors, IGF-1 sirtuin activators, mTOR, polyamines. current review discuss progress made involving these various strategies comment status future each exciting field.