PharmacoNutrition Reviewed

Source: Journal of Gerontology (Biol. Sci.) 63A (2008): 242-252
Article Type: Original Research
Authors: I Lenaerts et al.

When working with C. elegans myself (limited times though) I didn’t break my head too much about the pros and cons of feeding them with heat-inactivated E. coli as long as each plate contained the same amount of food.
Well, I maybe should have given it another thought, at least based on the latest article by Isabel Lenaerts and colleagues.

Here, the authors “…describe convenient ways to exert DR (dietary restriction) by culture on agar plates containing axenic (i.e., there is no microbial food source) medium. We used these to explore whether effects of axenic culture really reflect DR. Our results imply that major nutrient components of axenic medium, and overall caloric content, are not limiting for life span. However, adding growth-arrested Escherichia coli as an additional food source rescued the effects of axenic culture. We then sought to identify the component of E. coli that is critical for normal C. elegans nutrition using add-back experiments. Our results suggest that C. elegans has a nutritional requirement for live, metabolically active microbes or, possibly, an unidentified, heat-labile, nonsoluble component present in live microbes.”

Of note also, the addition of Daucus carota and Pisum sativum extracts to axenic medium, e.g., increased fecundity without affecting lifespan. In contrast, increasing concentrations of autoclaved or sonicated E. coli had no effect on offspring number.
Also, radiation-arrested but metabolically active E. coli rescued the effect of axenic medium. This, however, was just seen for low-dose radiated E.coli, indicating that “…as long as some metabolically active E. coli remained, rescue was possible. This finding suggests the surprising conclusion that metabolic activity in its microbial food source is a nutritional requirement for C. elegans.”

Almost everything known regarding C. elegans can be found here: wormbook.org

Source: Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Epub]
Article Type: Original Research
Authors: Martin-Gronert et al.

This is now the third time I am writing about the impact of in utero and early postnatal nutrition on fitness in later life.  Whereas before we learned some new insights in how changes in maternal dietary iron or fat might affect offspring life, the new paper by Martin-Gronert et al. addresses the question how dietary postnatal protein levels regulate key molecules believed to markedly control the aging process.

When pups of normally-fed dams were nursed by low-protein-fed (8% vs. 20% in the control group; iso-caloric diets) dams, dramatic biochemical changes (measured at day 21 post partum) occurred that might explain the earlier reported increased lifespan in these animals. The authors not only found that insulin sensitivity was improved but also a significant upregulation (measured in kidney tissue) of IRbeta, IGF1-R, Akt1, Akt2 as well as SIRT1. In addition, the expression of important antioxidant enzymes, i.e. catalase, CuZnSOD and GPx1, was elevated.

Martin-Gronert et al. conclude that “the findings of this study are in agreement with Hormesis Hypothesis, which has been proposed to explain the life-extending action of calorie restriciton. The hypothesis postulates that a low-intensity biological stressor exerts defence responses in the organism that help protect it against the causes of aging. The enhanced coping with intense stressors and restriction of senescent deterioration lead to retardation of age associated diseases and increased longevity. It seems that a similar process may underlie the association between early nutrition and the aging process.”

A candidate for the effect of restricted protein intake on lifespan has also been recently identified by Naudi et al.: methionine (whose restriction leads to upregulation of uncoupling proteins (UCP4) and an increase in mitochondrial biogenesis).

Poor mums-to-be: your burden of doing things right during pregnacy and nursing are certainly on the rise.

Image taken from: jupiterimages.com

Source: Neurobiology of Aging (2007), in press
Article Type: Original Research
Authors: A Bender et al.

Image taken from: http://www.scienceinafrica.co.za/pics/06_2004/brain.jpg

Creatine (an amino acid derivative) is a widely used food supplement due to its putative ergogenic, i.e. exercise capacity enhancing, effect. In terms of exercise performance, a recent review by Paddon-Jones and colleagues (J. Nutr. 134) concludes that creatine is suggested to be of benefit to exercise lasting 30 seconds or less; in contrast, no direct effect of creatine supplementation on muscle protein synthesis has been found. Nonetheless, creatine sales still reached US$ 220 million in 2005.
So whereas creatine might do rather little to improve exercise performance, it still seems to improve health. And not only this, but also survival – at least in mice. Based on previous reports demonstrating protective effects for creatine in models of neurodegeneration, Bender et al. tested the hypothesis whether creatine might also facilitate healthy aging, particularly of the brain, in wild-type mice. In essence, feeding mice a diet containing 1% creatine from 12-month of age onwards, significantly increased both mean and maximum life span in comparison to control mice. Somewhat confirming what was said already above, the creatine-fed mice did not differ in the rotarod and grip strength analyses; however, creatine feeding improved (p<0.05) several markers of memory performance such as object recognition. Also, biomarkers of brain aging due to oxidative stress tended to be lower in the creatine-fed group. Based on gene expression profiling experiments, the authors conclude that creatine not only reversely regulates gene expression altered in aging, but also concordantly affects gene expression as in mice on caloric restriction. Whether this effect of creatine is due to the induction of mild stress like in the case of caloric restriction is unknown. Another potential mechanism of creatine-induced neuroprotection might be the prevention of ROS (recative oxygen species) generation due to enhanced activity of mitochondrial creatine kinase activity, as recently shown by Meyer et al. (JBC 281).
In light of the rather minor safety concerns raised regarding creatine supplementation, it might be worth to further explore the potential of this amino acid derivative to improve healthy aging.

Source: Nutrition & Metabolism (2007), 4: 5 (Open Access)
Article Type: Original Research
Authors: W Zhou, P Murkerjee, MA Kiebish, WT Markis, JG Mantis, TN Seyfried

Image taken from:
http://3quarksdaily.blogs.com/3quarksdaily/images/brain_21.jpg

Ketogenic diets have been in clinical use for more than 80 years, primarily for the symptomatic treatment of epilepsy. In contrast to other organs, the brain almost exclusively needs glucose to satisfy its energy requirements. As an alternative, the brain can utilize ketone bodies for generating energy and fuelling its metabolism. Normal, healthy brain cells can better cope with this shift in energy source than tumour cells. Admittedly, to combat malignant brain cancer this way is a smart idea, especially as it appears so simple by using principles of evolutionary biology. And the concept works well, at least in this preclinical study on mice with implanted brain tumours. Mice fed a ketogenic diet displayed reduced glucose and enhanced ketone levels, finally causing the starvation of cancer cells. Cancer cells are also quite susceptible to oxidative stress; ketones, however, reduce the production of reactive oxygen species (ROS), as shown in neurons exposed to glutamate excitotoxicity (Maalouf et al.).
Of note, the same, i.e. the shift from glucose to ketone body metabolism, also happens in times of caloric restriction which has been shown to enhance the life span of many animal species.
All in all, the issue of using ketone bodies and ketonic diets for improving human health is quite promising, although much still needs to be done to fully understand the nature of their biological action.

In the February 01, 2007 edition of Sciencexpress, Libert et al. report on the regulation of Drosophila life span by olfaction and food-derived odors.

Image taken from:
http://athens.uchicago.edu/~lenka/images/drosophila-head.jpg

Caloric (dietary) restriction has been shown to modulate the lifespan of many different species, such as Drosophila m., C. elegans or rodents.
I find the fact that exposure to nutrient-derived odorants itself modulates lifespan quite intriguing and recommend for further reading the following two links: Science and The Scientist