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An In Ovo Model for Testing Insulin-mimetic Compounds

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Calorie Restriction Mimetics: Upstream-Type Compounds for Modulating Glucose Metabolism.

Hideya Shintani¹, Tomoya Shintani², Hisashi Ashida³

¹Department of Internal Medicine, Saiseikai Izuo Hospital, Osaka 551-0032, Japan. sntnhdy@gmail.com.

|November 25, 2018

Summary

Calorie restriction (CR) extends lifespan but is hard to maintain. This review explores CR mimetic (CRM) compounds, focusing on upstream-type CRMs that inhibit energy metabolism, particularly glucose, to achieve antiaging effects without CR.

Keywords:

2-deoxy-d-glucose SGLT2 inhibitor acarbose antiaging calorie restriction mimetics chitosan d-allulose d-glucosamine glucose metabolism modulation lifespan extension

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Area of Science:

Biogerontology
Metabolic pathways
Drug discovery

Background:

Calorie restriction (CR) is a proven method for extending lifespan in various organisms.
Long-term adherence to CR is challenging for humans, necessitating alternative strategies.
CR mimetic (CRM) compounds offer a potential solution by replicating CR's benefits without dietary restrictions.

Purpose of the Study:

To review current knowledge on compounds exhibiting CR mimetic (CRM) effects.
To categorize and focus on upstream-type CRMs that modulate energy metabolism.
To discuss the molecular definition and antiaging potential of these compounds.

Main Methods:

Literature review of compounds with CR mimetic effects.
Classification of CRMs into upstream-type (glycolytic inhibition) and downstream-type (signaling modulation).
Focus on upstream-type CRMs, analyzing their effects on energy metabolism, especially glucose.

Main Results:

Over 10 CRM compounds have been identified.
Upstream-type CRMs, including chitosan, acarbose, SGLT2 inhibitors, and hexose analogs (2-deoxy-d-glucose, d-glucosamine, d-allulose), demonstrate antiaging and longevity effects.
These compounds primarily act by inhibiting energy metabolism, particularly glucose metabolism.

Conclusions:

Upstream-type CRMs represent a promising class of compounds for achieving CR-like benefits.
Targeting glucose metabolism inhibition is a key mechanism for antiaging and longevity effects.
Further research into the molecular definition of upstream-type CRMs is warranted.