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Calorie restriction increases life span: a molecular mechanism
1Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA. nutritionreviews@ilsi.org
Nutrition Reviews
|March 16, 2006
Summary
Calorie restriction extends lifespan by activating Sirt1, which inhibits fat production. This reduction in adiposity is a key mechanism linking diet to longevity.
Area of Science:
- Molecular biology
- Metabolic research
- Aging research
Background:
- Calorie restriction (CR) is known to increase lifespan across diverse organisms.
- The silent information regulator 2 (Sir2) gene in yeast and its mammalian ortholog, Sirt1, are implicated in CR's effects.
- Sirt1 plays a role in white adipose tissue metabolism.
Purpose of the Study:
- To investigate the molecular mechanisms by which calorie restriction influences lifespan.
- To elucidate the role of Sirt1 in regulating adiposity under calorie restriction.
- To determine if Sirt1's inhibition of PPARgamma is a key pathway.
Main Methods:
- Investigated the role of Sirt1 in mammalian models.
- Analyzed the interaction between Sirt1 and peroxisome proliferator-activator receptor gamma (PPARgamma).
- Assessed the impact of Sirt1 activation on adipogenesis and lipolysis.
Main Results:
- Calorie restriction activates Sirt1 in mammals.
- Activated Sirt1 inhibits the function of PPARgamma, a promoter of adipogenesis.
- This inhibition leads to lipolysis and a reduction in fat mass.
Conclusions:
- Sirt1 activation by calorie restriction promotes fat loss through PPARgamma inhibition.
- Reduced adiposity is a significant mechanism contributing to the lifespan-extending effects of calorie restriction.