Energy restriction and potential energy restriction mimetics

Area of Science:

• Gerontology
• Nutritional Science
• Pharmacology

Background:

• Energy restriction (ER), or caloric restriction, is a proven method to increase lifespan in model organisms and may delay human aging.
• Understanding the molecular, metabolic, and hormonal effects of ER is crucial for developing anti-aging strategies.

Purpose of the Study:

• To review the scientific literature on energy restriction (ER) and its effects.
• To summarize criteria for classifying substances that mimic ER effects (ERM) without reducing caloric intake.
• To discuss potential ERMs, their molecular targets, and their efficacy and safety in higher organisms.

Main Methods:

• Literature review of scientific studies on energy restriction and its mimetics.
• Analysis of molecular, metabolic, and hormonal effects associated with ER.
• Evaluation of data on lifespan extension and safety of ERM candidates in model organisms and higher organisms.

Main Results:

• ER is the only nutritional intervention consistently shown to extend lifespan in model organisms.
• Several ERM candidates (e.g., metformin, resveratrol) show promise in model organisms but have controversial or missing data in higher organisms.
• Some ERMs have significant side effects (e.g., immunosuppression, lactic acidosis) or lack long-term safety data.

Conclusions:

• No current ERM can be recommended without limitations for human use due to inconsistent efficacy and safety concerns.
• Further research is needed to identify safe and effective ERMs for human longevity and aging delay.
• The development of safe ERMs remains a significant challenge in gerontology and nutritional science.