Nutrigenomics: What We Eat Affects Our Genes and also Our Lifespan

Two topics of clinical significance to everyone are aging and cancer. We, of course, cannot stop the aging process completely but there are easy and inexpensive ways to reduce the cellular ravages of time and thus delay the overall aging process. And coupled to aging is the dreaded disease, cancer in all its ugly and devastating forms. As populations age, as well as die at older ages than say as little as 50 years ago, the rates of many cancers increases. Indeed, the events of aging that occur at the cellular level are intimately linked to the events that lead to the likelihood for cancer to arise.

Numerous scientific and clinical studies have been carried out demonstrating that aging, and conditions related to the aging process, can be manipulated and/or modified by both the environment, in particular what we eat, and our genes. Of significance to the clinical consequences of aging are the facts that dietary habits can manipulate the aging process and as a result may have exert unprecedented health benefits. The beauty of this correlation is that diet does not require expensive drugs or other invasive therapeutic interventions to achieve a healthier longer lifespan. The underlying concept of dietary control of, or influence on, cellular aging is embedded in a concept referred to as nutrigenomics. The term nutrigenomics refers to the impact of food and the components in food that impact the pattern of genes that are expressed. The concepts that underlie nutrigenomics assume that bioactive components in  food can directly or indirectly influence gene expression and as a result lead to changes in the state of health and disease of an individual.

Dietary components and dietary lifestyle have been shown to impact several avenues of the overall cellular aging process. Mammalian aging is the result of the accumulation, over time, of a variety of forms of both molecular and cellular damage. One major contributor to aging is oxidative stress. In this context oxidative stress refers to the accumulation of damaged biomolecules, such as lipids, proteins and nucleic acids, that results from the action of the highly reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS are often referred to as free radicals and include hydrogen peroxide, superoxide anion, and the very damaging hydroxy radical. With respect to diet and aging, the beneficial effects of a diet restricted in total caloric intake have been quite striking in certain experimental systems, although only limited benefits have, thus far, been shown in humans. Another important regulator of cellular aging that can be affected by diet is the stability of the chromosomes in the cell. All chromosomes have a unique structure at each end called the telomere. When cells divide the telomeres require a special enzyme system for reproduction (DNA replication) and even with this system in place the length of the telomeres shortens with each division and at a critical length triggers a programmed cell death process. Dietary constituents have been shown to affect the activity of the telomere replicating machinery (telomerase) as well as the integrity of the telomeres themselves.

Altering Oxidative Stress with Diet:

A basal level of oxidative stress is essential for cell survival. An easy way to appreciate this concept is discuss the process of immune cell-mediated killing of invading pathogens such as bacteria. Phagocytic cells, such as neutrophils, have an enzymatic mechanism to generate ROS to kill the bacteria these cells have taken up via the phagocytic process. Even so, the accumulation of excess ROS will lead to o widespread oxidative damage and ultimately cell death. Unfortunately cellular oxidative stress accumulates as we age, significantly contributing to the overall process of cellular aging. This age-relatred ROS damage accumulation results from a combination of time of exposure to ROS and RNS, and to a progressive decline natural antioxidant processes.  With respect to diet, numerous bioactive food components, including plant-derived polyphenols, isoflavones, curcumin, and resveratrol (e.g. red wine), for example have been reported to reduce oxidative stress and as a consequence reduce the incidence of inflammation, cardiovascular disease, and cancers.

For more details on dietary supplements/food components as antioxidants and anti-aging compounds visit my Supplement Science website:

As an example, curcumin has been shown to upregulate the expression of natural antioxidant enzyme genes while downregulating several aging related genes. The life extension capacity of curcumin (as well as other antioxidant food components) may not be solely due to its potential to activate antioxidant programs but is likely also due to potential alterations in the epigenetic program of the cell. Epigenetics refers to a visible phenotype being observed in the absence of any change in the nucleotide sequences in the genome. The two epigenetic processes are DNA methylation and histone protein modification. Dietary constituents have been clearly shown to affect the epigenome (another upcoming blog topic). Dietary constituents in combination, such as ascorbate (vitamin C), the amino acids lysine, proline, and arginine, and the metals selenium, copper, manganese, and calcium have also been shown to alter the pattern of antioxidant enzyme expression in animal model of aging.

Calorie Restriction:

Calorie restriction, as it relates to a viable dietary program, does not mean malnutrition. The effects of calorie restriction have been clearly associated with lifespan extension in a variety of lower organisms. In several animal models it has been found that caloric restriction increases life span while simultaneously decreases the risk of certain diseases. In humans calorie restriction may not, in and of itself, lead to an increase in lifespan under all conditions, but in persons who consume too many calories a restriction in intake clearly has health benefits. Not only calories themselves, but the source of calories, has a profound effect on feeding behavior and the negative health consequences of excess caloric intake. Fats and carbohydrates are metabolized in the brain and the consequences of those processes impact the continued, or lack, desire to consume food. These signals have many facets that constitute neurotransmitters and neurohormones but one major regulator is the melanocortin system. This system constitutes hormones and the receptors to which these hormones bind. For more details I recommend a visit to the Gut-Brain Interrelationships page of my other website:

Genetic variation in one of the melanocortin receptors (MC4R) has a significant correlation to a high risk for obesity. Even without a genetic predisposition, dietary constituents influence the melanocortin systems in the brain, as well as other appetite regulating neurotransmitter pathways. High-fat diets tend to result in the activation of hunger signals, whereas as glucose metabolism on the brain is known to suppress hunger and induce a sensation of fullness (satiety). Another genetic factor associated with obesity is variations in the gene encoding a transcription factor called PPARgamma. This transcription factor is capable of turning on a program of cell differentiation into fat cells (adipocytes). PPARgamma controls the expression of multiple genes involved in
cellular differentiation, lipid storage, and insulin sensitization. Of significance to this discussion is the fact that a variety of different dietary components such as the all important omega-3 polyunsaturated fatty acids (EPA and DHA: read my prior blog post on these important dietary lipids) and several plant-derived compounds (e.g. capsaicin, luteolin, naringenin, and resveratrol) have been shown to affect PPARgamma activity.

Telomere Integrity and Diet:

Telomeres are specialized structures located at the ends of each of the eukaryotic
chromosomes. The telomeres are essential for genomic stability and they naturally shorten after each round of DNA replication. As their length shortens the telomeres act as biological markers for cell age. At some telomere length a program of cell death (apoptosis) is activated. In addition, telomere length may reflect the cumulative burden of oxidative stress and inflammation accelerating the age of a cell leading to earlier activation of apoptosis. Dietary composition, such as the inclusion of antioxidants can protect the telomeres from oxidative damage and, consequently extend cellular lifespan. Specifically, the consumption of the omega-3 fatty acids, folate, vitamin B12, nicotinamide (vitamin B3), vitamins A, C, D, and E, iron, magnesium, and zinc, and plant-derived polyphenols and curcumin have been reported to be associated with telomere length. Indeed, drinking coffee has been shown to be associated with preservation of telomere length as I recently posted.

The replication of telomeres requires a multisubunit complex that includes an enzyme called telomerase. Just as telomere length will induce apoptosis, so too will reduction or loss of telomerase activity. Conversely, too much telomerase activity can prevent required cell death and this is, in fact, found in numerous types of cancer. Certain dietary components such as genistein and epigallocatechin gallate (e.g. green tea) have been reported to affect the level of telomerase activity.

So what exactly is the TAKE HOME from reading this post?? As I'm sure many of you have heard "you are what you eat" and indeed as more and more clinical and scientific date shows, you may be an older healthier you if you take ownership of what you eat. After all it is so much cheaper to be healthy by eating than by going to the doctor all the time and paying for EXPENSIVE (or dangerous illicit) pharmaceuticals.


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