Age related diseases put a heavy burden on health care systems world-wide.
Using chemical and biological systems we are investigating whether chemicals found in plants can prevent or reverse the effects of aging and unhealthy diets.
This research can inform the food industry how their products can be made healthier by addition of natural bioactive substances.
In the Western world nutrition is a major environmental factor determining long term health outcomes. The major disease outcomes include obesity, type II diabetes and cardiovascular disease and are collectively described as metabolic syndrome.
Some health outcomes are influenced by persistent nutritional deficiencies over a long period of time; however, other health outcomes are elicited by nutritional insults during critical windows of development.
We are investigating the impact of two nutritional parameters, B-vitamins and dietary protein, on long term health outcomes and want to understand how these nutritional parameters influence metabolic health. We are especially interested whether epigenetic processes are instrumental in programming these long term health outcomes.
B-vitamins are important for cell survival and were originally described as remedies for anemia. A good B-vitamin status, especially sufficient levels of folate, is critical during early phases of pregnancy, where it can protect against the occurrence of neural tube defects. For this reason several countries have introduced mandatory fortification of flour with folic acid.
Epidemiological findings suggest that low B-vitamin status is also a risk factor for cardiovascular disease. However folic acid supplementation in patients already suffering from vascular disease by and large does not improve health outcomes. This suggests that a persistent low B-vitamin status throughout life leads to physiological changes which are irreversible by the time vascular disease becomes overt.
We have investigated the physiological links between B-vitamin status and vascular disease. We could show that B-vitamin deficiency leads to an increase in inflammatory mediators and a decrease in the production of the vaso-protective chemical nitric oxide. We therefore conclude that B-vitamin deficiency promotes the inflammatory processes which are causally involved in development of cardio-vascular disease.
We are also investigating the influence of protein supply during early life on long term metabolic health. Epidemiological data have demonstrated that excessive growth rates during early postnatal life are associated with an increased risk of obesity and type II diabetes in later life. Protein acts as an important promoter of growth during early life. One reason why breastfeeding provides significant long-term health benefits over formula feeding may therefore be related to the lower concentration of protein in breast milk compared to formula. This typically leads to a lower growth rate of breastfed babies compared to bottle-fed babies.
We and others have demonstrated in animal model systems that a reduced growth rate during early postnatal life leads to significant improvements in long-term metabolic health and a lifespan extension by around 25%. We are currently investigating the physiological mechanisms underlying this phenomenon. An improved understanding of the physiological mechanism may allow us to devise nutritional or pharmaceutical interventions which mimic the biological effects of attenuated growth during early life.
Kolb, A.F., Petrie, L. (2013) “Folate deficiency enhances the inflammatory response of macrophages.” Molecular Immunology, 54 (2) pp. 164-172
Kolb, A.F., Sorrell, D., Lassnig, C., Lillico, S., Carlisle, A., Neil, C., Robinson, C., Muller, M., Whitelaw, C.B.A. (2013) “Mammary gland development is delayed in mice deficient for aminopeptidase N” Transgenic Research, 22 (2) pp. 425-434
Huber, R.C., Kolb, A.F., Lillico, S., Carlisle, A., Sandoe, P., Sorensen, D.B., Remuge, L., Whitelaw, B.C.A., Olsson, A.I.S. (2013) “Behaviour of postnatally growth-impaired mice during malnutrition and after partial weight recovery.” Nutritional Neuroscience, 16 (3) pp. 125-134
Kolb, A.F., Huber, R..C., Lillico, S.G., Carlisle, A., Robinson, C.J., Neil, C., Petrie, L., Sorensen, D.B., Olsson, I.A.S., Whitelaw, C.B.A. (2011) “Milk lacking alpha-casein leads to permanent reduction in body size in mice.” PLoS One, 6 (7 Art. e21775)
Proudfoot, C., McPherson, A.L., Kolb, A.F., Stark, W.M. (2011) “Zinc finger recombinases with adaptable DNA sequence specificity.” PLoS One, 6(4 Art. e19537)
Sorrell, D.A., Robinson, C.J., Smith, J.A., Kolb, A.F. (2010) “Recombinase mediated cassette exchange into genomic targets using an adenovirus vector.” Nucleic Acids Research, 38 (11 Art. e123)