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Updated: Nov 30, 2025
An Optimized Protocol to Analyze Glycolysis and Mitochondrial Respiration in Lymphocytes
Published on: November 21, 2016
Glycolytic inhibition: an effective strategy for developing calorie restriction mimetics
Donald K Ingram1, George S Roth2
1Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA, 70809, USA. donald.ingram@pbrc.edu.
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.
Insights
Calorie restriction mimetics aim to replicate anti-aging benefits without dietary changes. This review focuses on glycolytic inhibition strategies, exploring compounds like 2-deoxyglucose for potential anti-aging, anti-cancer, and anti-obesity effects.
Area of Science:
- Biochemistry
- Gerontology
- Pharmacology
Background:
- Calorie restriction (CR) extends lifespan and healthspan by activating conserved cellular pathways.
- Developing CR mimetics offers a non-dietary approach to harness CR's benefits.
- Glycolytic inhibition is a key upstream strategy to mimic CR's effects.
Purpose of the Study:
- To review approaches targeting glycolytic inhibition as a CR mimetic strategy.
- To highlight compounds investigated for their potential to induce CR-like effects.
- To discuss anti-cancer and anti-obesity applications of these inhibitors.
Main Methods:
- Literature review of scientific publications on CR mimetics.
- Focus on compounds inhibiting intracellular glycolysis.
- Analysis of selected compounds including 2-deoxyglucose, 3-bromopyruvate, and resveratrol.
Main Results:
- Glycolytic inhibition is a promising strategy to activate CR-induced anti-aging mechanisms.
- Several compounds show potential, but results vary, with some extensively studied and others emerging.
- Anti-cancer and anti-obesity effects are key considerations in evaluating these candidates.
Conclusions:
- Glycolytic inhibitors represent a significant area of research for developing CR mimetics.
- Further investigation is needed to optimize efficacy and safety of these compounds.
- Targeting glycolysis offers a potential route to anti-aging, anti-cancer, and anti-obesity therapeutics.
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