Metabolic Effects of Caloric Restriction

Joseph A Baur, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Published online: March 2009

DOI: 10.1002/9780470015902.a0021316

Caloric restriction (CR) improves health and increases longevity in organisms from yeast to mammals. Studies in rodent models show that CR suppresses a wide range of diseases that contribute to human morbidity and mortality such as cancer, cardiovascular disease and diabetes. Although the metabolic and physiological changes induced by CR have been investigated for over 70 years, the precise mechanism by which it is able to slow the progression of age-related degeneration remains a subject of much debate. This article summarizes our current understanding, including recent findings that implicate specific enzymes and signalling pathways in the process. Further study of CR may provide insight into the nature of aging and reveal new opportunities to improve the quality and quantity of human life.

Key concepts

  • Reducing energy intake in the absence of malnutrition (caloric restriction) improves health and extends longevity.
  • Caloric restriction causes widespread changes in physiology and metabolism, many of which are distinct from fasting responses.
  • Manipulation of specific genetic pathways can block or mimic some responses to caloric restriction.
  • Insulin/IGF-1 signalling is consistently implicated in the mechanism of caloric restriction.
  • Neither aging nor its retardation by caloric restriction is understood, however much of the available data is compatible with the Free Radical Hypothesis.

Keywords: dietary restriction; aging; longevity; healthspan; sirtuins; mitochondria

Figure 1. Pathways that have been proposed to mediate effects of caloric restriction. Red arrows indicate transcriptional effects. Arrows pointing at posttranslational modifications indicate direct effects that are mediated by a change in that modification (Ac, acetylation; P, phosphorylation). For clarity, only relevant steps of the insulin-signalling pathway are shown. A key feature of this diagram is the preponderance of redundant and reinforcing signals. However, it should be noted that findings from many sources have been combined, and that only a subset of these pathways may be active in any given tissue. Thus, redundancy may indicate a coordinated response, or may be an artefact of combing signals that are active in and between different cell types. Putting the various signals that mediate effects of CR into the proper context in terms of tissue, timing and causality will be crucial if a better understanding is to be reached.
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Related Sub-Topics:

Intracellular and Extracellular Signalling | Cell Biology of Cancer | Cell Death and Cellular Senescence | Cell Signalling | Bioenergetics
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Article Title: Metabolic Effects of Caloric Restriction
 
How to Cite close
Baur, Joseph A(Mar 2009) Metabolic Effects of Caloric Restriction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021316]