PharmacoNutrition Reviewed

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: Am. J. Physiol. Heart Circ. Physiol. 04 JAN 2008 [Epub]
Article Type: Original Research

Authors: Angeloni et al.

 

 

 

The flavonoid quercetin (QU) is among the most common polyphenols found in the human diet. In the present study, Angeloni et al. assessed the in vitro effect of QU on the expression of more than 20.000 genes in cardiomyocytes.

The data, also this has not been directly discussed by the authors, suggest a hormetic effect of QU in this cell culture model, evident by the modulation of various phase II enzymes (such as HSP-32). These proteins, in turn, indirectly affect the cellular antioxidant defense system. i.e. render the cells better equipped for the occurrence of oxidative stress.

Although, in contrast to the authors, I think that the QU concentration tested (30 microM) is rather high (and certainly not in the physiological range), the article provides various interesting targets for the modulation of oxidative stress resistance of cardiomyocytes.

Let’s hope somebody dares to make the next step and assesses the impact of orally administered QU (and related flavonoids) and gene expression under in vivo conditions.

Image taken from: www.3dscience.com

Source: Trends in Neuroscience (2006), 29: 632-639
Article Type: Review
Authors: MP Mattson, A Cheng

Image taken from: http://www.bad-bad.de/gesch/paracel.gif

Recently, the hormesis theory is gaining momentum for explaining the health-beneficial effects of diets rich in fruits and vegetables. Actually, one of the first to describe hormetic effects of any substance applied to living things has been Paracelsus, one of the most famous scientists of the 16th century.
What is hormesis? The term describes the induction of health-beneficial effects due to the low-dose presence of agents that are toxic at higher concentrations (adaptive response). In this regard, phytochemicals (such as polpyhenols) can be considered as mild stressors provoking the up-regulation of the endogenous antioxidant network. This in turn would enable an organism to better cope with an increasing production of reactive oxidative and nitrosative species (ROS and RNS), for example in disease states. Consequently, the detrimental degeneration of proteins, fatty acids, sugars and DNA would be avoided. In the long run, this could finally lead to a healthier aging process, characterised by a lower burden of chronic, lifestyle maladies. Mattson and Cheng support this concept by summarising recent data obtained with, amongst others, the neurohormetic phytochemicals resveratrol and curcumin in vitro and in vivo.

Personally, I feel quite comfortable with this theory. However, whether it will help to answer the recurring question of whether an increase/decrease in biomarkers such as antioxidant capacity or antioxidant enzyme activity upon incubation/intake of phytochemicals is actually beneficial or detrimental, only time will tell.

For further reading, I recommend: Arumugam et al., 2006 and Hipkiss, 2006 and Hayes, 2007.