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Glycolytic inhibition: an effective strategy for developing calorie restriction mimetics

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Abstract

Calorie restriction mimetics encompass a growing research field directed toward developing treatments that mimic the anti-aging effects of long-term calorie restriction without requiring a change in eating habits. A wide range of approaches have been identified that include (1) intestinal inhibitors of fat and carbohydrate metabolism; (2) inhibitors of intracellular glycolysis; (3) stimulators of the AMPK pathway; (4) sirtuin activators; (5) inhibitors of the mTOR pathway, and (6) polyamines. Several biotech companies have been formed to pursue several of these strategies. The objective of this review is to describe the approaches directed toward glycolytic inhibition. This upstream strategy is considered an effective means to invoke a wide range of anti-aging mechanisms induced by CR. Anti-cancer and anti-obesity effects are important considerations in early development efforts. Although many dozens of candidates could be discussed, the compounds selected to be reviewed are the following: 2-deoxyglucose, 3-bromopyruvate, chrysin, genistein, astragalin, resveratrol, glucosamine, mannoheptulose, and d-allulose. Some candidates have been investigated extensively with both positive and negative results, while others are only beginning to be studied.

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  1. Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA, 70809, USA

    Donald K. Ingram

  2. GeroScience, Inc., 1124 Ridge Road, Pylesville, MD, 21132, USA

    George S. Roth

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Donald K. Ingram is a stockholder and serves as Chief Scientific Officer for GeroScience and Prolongevity Technologies. Both companies are directed toward developing glycolytic inhibitors as an anti-aging intervention. George S. Roth is a stockholder and serves as Chief Executive Officer for GeroScience and Prolongevity Technologies. Both companies are directed toward developing glycolytic inhibitors as an anti-aging intervention.

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Ingram, D.K., Roth, G.S. Glycolytic inhibition: an effective strategy for developing calorie restriction mimetics. GeroScience 43, 1159–1169 (2021). https://doi.org/10.1007/s11357-020-00298-7

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