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Review
. 2009 Feb 5;299(1):129-36.
doi: 10.1016/j.mce.2008.10.014. Epub 2008 Oct 21.

Endocrine alterations in response to calorie restriction in humans

Leanne M Redman  1 , Eric Ravussin
Affiliations
Review

Endocrine alterations in response to calorie restriction in humans

Leanne M Redman et al. Mol Cell Endocrinol. .

Abstract

This review focuses on research involving calorie restriction (CR) in humans and the resulting changes observed in endocrine and neuroendocrine systems. Special emphasis is given to the clinical science studies designed to investigate the effects of controlled, high-quality, energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases of human aging. Prolonged CR has been shown to extend both the median and maximal lifespan in a variety of lower species such as yeast, worms, fish, rats and mice. The biological mechanisms of this lifespan extension via CR are not fully elucidated, but possibly involve significant alterations in energy metabolism, oxidative damage, insulin sensitivity and functional changes in both neuroendocrine and autonomic nervous systems. Most of the difficulty in characterizing the systemic endocrine and neuroendocrine changes with aging and CR is due to the limited capability to collect large and multiple blood samples from small animals, which are usually shorter lived, and hence the most studied. Ongoing studies of prolonged CR in humans are now making it possible to analyze changes in the "biomarkers of aging" to unravel some of the mechanisms of its anti-aging phenomenon. With the incremental expansion of research endeavors in the area of energy restriction, data on the effects of CR in non-human primates and human subjects are becoming more accessible. Detailed analyses from controlled human trials involving long-term CR will allow investigators to link observed alterations from body composition and endocrine systems down to changes in molecular pathways and gene expression, with their possible effects on aging.

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Figures

Figure 1
Figure 1. Impact of calorie restriction on factors related to aging
Non-mutually exclusive candidate mechanisms of CR include: Decreased oxidative damage due to reduced ROS generation and increased ROS removal; altered neuroendocrine function including growth hormone axis, thyroid axis, hypothalamic pituitary axis, autonomic nervous system, and carbohydrate metabolism; decreased incidence of chronic diseases such as obesity, diabetes and cardiovascular disease; and delayed onset of aging-related markers (i.e., glucose, insulin, DHEA-S and body temperature). Aging is then marked by changes in endocrine function which could occur as a result of the primary mechanisms of aging, or secondary due to lifestyle (nutrition and exercise) factors.
Figure 2
Figure 2. Can calorie restriction improve biological age and extend chronological age?
This figure illustrates three validated biomarkers of longevity. It is hypothesized that calorie restriction will change the trajectory of these biomarkers and therefore improve biological age and extend chronological age. For example, the left panel shows an individual aged 75 years who engages in prolonged calorie restriction from age 25 would have a reduced plasma insulin concentration which corresponds to a biological age 14 years younger. Similarly, the individual on the right at 90 years with prolonged calorie restriction will be biologically similar to an individual aged 66 years.
See this image and copyright information in PMC

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