Diet, phytochemicals and age-related diseases
Published on 25 September 2012 in Food, health and wellbeing
Introduction
In the past two centuries a gradual improvement in health care and nutrition has led to a dramatic increase in life expectancy, especially in the developed world. It is expected that by 2033 one in four people will be over the age of 65. As the increase in life-span has not been entirely matched by an increase in health-span (the time in which an individual lives without any "serious" disease), a larger proportion of elderly people will require treatment for age-related diseases, including diabetes, atherosclerosis, cancer and dementia.
These diseases are characterised by a number of physiological changes, amongst which two have been found to be of great significance, namely insulin sensitivity and inflammation. Ageing is associated with a reduced output of insulin from the pancreas, and a reduced sensitivity of the peripheral tissues (like liver and skeletal muscle) to insulin. That means that less sugar is taken up into the cells and remains in the blood where excess sugar can have detrimental impacts on tissues and cells. Similarly a steady-state chronic inflammation is more prevalent in older people, leading to an increased susceptibility to atherosclerosis.
However, individuals vary in their sensitivity to insulin and in their inflammation status. This is due to environmental factors (like diet) but also due to the genes of the individual. It has been shown that that some gene variants which improve insulin sensitivity and reduce inflammation occur more frequently in centenarians. This suggests that these genetic predispositions support a long life-span. The relevance of these genetic differences can also be verified in animal model systems.
Diet is a major factor which can significantly alter insulin sensitivity and inflammation. There are two known dietary interventions which have been demonstrated to significantly increase health-span in animal model systems and may also be effective to ameliorate the impact of age-related diseases.
Firstly, caloric restriction (a nutrition which is sufficient in all micronutrients, vitamins and minerals but has a reduced content of calories) is effective in a variety of organisms from fruit-fly through to mouse and rhesus monkeys. It significantly improves insulin sensitivity, reduces susceptibility to cancer and, as a consequence, extends life-span and health-span. Secondly, attenuation of nutrition during early phases of post-natal life leads to significant extension of life-span and health-span in rodent model systems.
Whilst these interventions may not be directly applicable to the human situation they have enabled the identification of physiological mechanisms which can be modulated by dietary interventions to ameliorate age-related diseases and extend human health-span.
Key Points
- Ageing is associated with reduced insulin sensitivity, increased inflammation and reduced ability to respond to metabolic stress.
- Nutritional interventions like caloric restriction and early postnatal growth attenuation are able to ameliorate the effects of age related disease.
- Dietary components like phytochemicals may have the potential to mimic the effects of caloric restriction and growth attenuation.
Research Undertaken
The effects elicited by caloric restriction and the attenuation of early nutrition have potential to ameliorate the impact of age-related diseases. Although they cannot be tested directly in the human situation some epidemiological findings have supported their effectiveness in humans. There is evidence that high growth rates early in life are associated with an increased susceptibility to obesity and diabetes. The current scientific consensus also suggests that the better health outcomes of breast-fed infants in comparison to bottle-fed infants is due (at least in part) to the lower growth rate of breast-fed babies in early post-natal life.
In order to identify the physiological mechanisms which link early growth rates with long term health outcomes we have established a model system in which these associations can be analysed. Guided by these data we are developing assay systems in which dietary components derived from selected vegetables and soft fruit can be assessed for the potency to ameliorate age-related diseases.
Interestingly some effects elicited by caloric restriction and growth restriction can be replicated by chemicals. Several studies in animal models systems have demonstrated that rapamcyin (a bacterial metabolite originally used in the clinic as an antifungal agent and immune-suppressant) can extend the lifespan in mice. Some studies have suggested that similar effects can be elicited by phytochemicals (like resveratrol and curcumin). This suggests that there is an as yet untapped reservoir of natural chemicals which can ameliorate the impact of age-related diseases.
Using in vitro systems we are also directly investigating how insulin sensitivity and inflammation can be impacted by dietary interventions. We and others have demonstrated that the polyphenolic substances, like curcumin, can significantly reduce inflammation and improve insulin sensitivity in model systems.
Several trials are currently assessing the effectiveness of curcumin against some age-related diseases. Using in vitro analysis systems we have also found that B-vitamins have the potential to reduce inflammation and promote the generation of substances which are protective for the vascular system. These data may explain, at least in part, the beneficial effects of B-vitamins on vascular disease.
Policy Implications
Our evidence will assist in the development of nutritional recommendations to ameliorate age-related diseases. The assay systems being developed will aid in the identification of food properties to direct plant breeding of the appropriate crops towards key chemical constituents. The assay systems can also be used to support food processing towards foodstuffs with anti-aging properties and are directly relevant for the Scottish Food and Drink strategy.
The evidence gathered in our model systems will also improve our understanding of the links between nutrition in early life and later health outcomes.
Authors
Dr Andreas Kolb A.Kolb@abdn.ac.uk
Dr Rex Brennan Rex.Brennan@hutton.ac.uk
