Nutritional Role of Aging and Cancer Prevention Through Epigenetics
By Dr. Millie Lytle, ND, MPH, CNS Follow on Google+
The field of genetics involves the material make-up of your genes; DNA, chromosomes and RNA housed within each cell. What you have inherited from your parents and their parents before determines if you are a human or a carrot. It also determines more precise characteristics such what sex you are, what skin, eye and hair color you have as well one’s disposition. Are you nimble with a pen, an engine, a needle and thread, a football or a violin? Notably, your genes are also related to whether you are at risk for certain diseases such as autoimmune and cancer. While genetics create some fixed realities about you, they don’t explain everything.
The field of epigenetics is a new and emerging one and finally, it is a response to the nature versus nurture debate. The answer is: BOTH. You are a combination of the genetic material you inherit and you are the result of how you develop according to your surroundings. You see, the field of epigenetics involves the behavior of genes. Even though you may have a gene that puts you in the upper 5th percentile at risk for Lupus or breast cancer you may not get that disease. Every other member of your family could have a particular genetic condition and you might escape it, or vice versa.
Dr. Bruce Lipton, cell biologist and professor of medicine, writes in his book The Biology of Belief1, that the error in genetics research has been made in analyzing only the DNA itself without looking at the cytoplasm or the cellular material surrounding the genes. A gene may be present, but it will only be expressed under a certain set of circumstance or in a particular environment. Environmental factors that participate in the on and off behavior of your genes include nutrition, lifestyle and even quality of thought.
Further research has been done into the field of epigenetics and has proven in several laboratory, animal and human studies that a series of factors of genes called peroxisome proliferator-activated receptors (PPARS) are partially responsible for genetic ‘ON’ and ‘OFF’ switches to control nutritionally-related chronic disease.2 PPARs act through the regulation of numerous biological processes, including fat and sugar metabolism and overall energy balance (homeostasis). Importantly, PPARs also mediate the inflammatory response, which makes them a possible therapeutic target to reduce obesity-induced inflammation and its serious health burden.3 PPAR activity have been associated with a list of chronic diseases.2 PPARs have been implicated in the cause as well as treatment of atherosclerosis, diabetes, hyperglycemia, obesity, regulation of fertility, central nervous system conditions of myelination and various types of cancer, and more. Over the recent years a lot of exciting research has shown certain nutritional ingredients can impact PPARs activation and gene expression to prevent and treat some of the most common chronic diseases.
Pterostilbene is the brain antioxidant from the the “brainberry”, blueberry (Vaccinium sp.). Results from in vitro studies have shown that pterostilbene promotes PPARalpha and may be an effective lipid lowerer, even more effective than its cousin resveratrol for brain conditions. In vivo studies, performed in the body, have demonstrated that this powerful antioxidant has fat (cholesterol) and blood sugar lowering effects.5 In another study, blood markers of cellular stress, inflammation, and Alzheimer’s disease pathology were positively lowered by pterostilbene via PPARalpha expression, providing protection from age-related brain conditions. In summary, research results indicate that doses of pterostilbene, achievable in the diet and supplement form, are potent modulators of cognition, memory and cellular stress, due to increased PPAR alpha expression and fat solubility of pterostilbene, meaning the antioxidant can be active in brain tissue.6
Chlorella, along with spirulina, is a member of a group of tiny blue-green algae that are highly nutritious due to their nutrient content and biological capabilities. It has long been known that chlorella contains B vitamins, minerals and detox factors, however genetic studies are showing they also contains fatty acids that are healthy for the body. The bioactivities of several healthy fats contained within Chlorella sorokinana were evaluated for their PPARgamma activity. Impressive results showed that linolenic acid (Omega 3, algaeDHA) and linoleic acid (Omega 6) were the most potent fatty acids. Fatty acids such as Omega 3 and 6 can contribute to fat regulation in the body, such as cholesterol lowering. Algae DHA is also associated with positive effects for brain mass, memory and learning. Chlorella sorokiniana could have potential health benefits both through activation of PPARalpha and gamma as well as via its unique algae constituents.7
Green tea (Camellia sinensis) is one of the most studied herbs for its panacea of benefits. And the research is moving into the field of gene expression. In one recent study it was demonstrated that a single, high dose of green tea extract prevented the overproduction of Nitric Oxide (NO) in the heart cells of newborns. While NO is healthy for blood vessel relaxation, an overproduction is related conditions such as atherosclerosis, whereby inflammation in the arteries produces too much NO (i.e. too much of a good thing can be bad for health). In a follow up study that looked at how green tea extract treats an overproduction of NO, it was observed that green tea extract’s antioxidant activity and PPAR-beta and delta activation were key to its therapeutic effect.8 Green tea therefore has great potential in the ability to alter gene expression for heart and blood vessel disease through its PPAR and antioxidant activity.
Acetyl L-Carnitine and Alpha Lipoic Acid
Acetyl L-Carnitine and Alpha Lipoic Acid are two amino acid-like nutrients that have been shown again and again to work well together. One study demonstrated that defective fat and cholesterol metabolism are associated with low mitochondrial quality and activity in skeletal muscle of the diabetic Goto-Kakizaki rats, thereby leading to metabolic syndrome, obesity and diabetes. When diseased rats were treated with a combination of R-alpha-lipoic acid, acetyl-L-carnitine and two B Vitamins (nicotinamide and biotin) the nutritional protocol effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid, as well as maintained mitochondria health for the muscle itself. The nutrient protocol also significantly increased genetic tissue involved in lipid metabolism, including PPARalpha and delta activity of skeletal muscle mitochondria. All of these improvements on mitochondrial nutrients were shown to be comparable to that of the anti-diabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain.9 Treatments with the combination of alpha lipoic acid and acetyl l-carnitine for a little as 24 hours significantly increased mitochondrial mass, expression of mitochondrial DNA, mitochondrial complexes, oxygen consumption and fatty acid oxidation in fat cells. These changes were accompanied by an increase in expression of PPARgamma, PPARalpha and Cpt1a mRNA, as well as increased expression of PPAR gamma coactivator 1 alpha (PPARgc1a), mitochondrial transcription factor A (Tfam) and nuclear respiratory factors 1 and 2 (Nrf1 and Nrf2).9
So…in summary, you inherit the DNA structure and geneology from your parents; when you are born you are the sum of your parents’ state of health at conception, the health of your mother during pregnancy, her level of stress and any medical incident at the time of birth. Additionally, as soon as you are born your experiences and environment shape how your genes will continue to change, making you an individual with his or her own set of genetic factors. From the research cited above, nutrition and dietary supplements play a key role in the etiology or cause of genetic conditions, proving great promise for a wide range of the most concerning, yet preventable, chronic conditions from anti-aging to diabetes to heart disease to cancer.
- Lipton, BH. The Biology of Belief. Unleashing the Power of Consciousness, Matter, & Miracles. 2008. Hay House: USA.
- Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med. 2002;53:409-35.
- Youssef J, Badr MZ. PPARs: history and advances. Methods Mol Biol. 2013;952:1-6.
- Stienstra R, Duval C, Müller M, Kersten S. PPARs, Obesity, and Inflammation. PPAR Res. 2007; 2007: 95974.
- Rimando AM, Nagmani R, Feller DR, Yokoyama W. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem. 2005 May 4;53(9):3403-7.
- Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt-Hale B, Smith MA, Joseph JA, Casadesus G. Neurobiol Aging. Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease. 2012 Sep;33(9):2062-71.
Bioassay-guided purification and identification of PPARalpha/gamma agonists from Chlorella sorokiniana. Phytother Res. 2008 May;22(5):605-13.
- Danesi F, Di Nunzio M, Boschetti E, Bordoni A. Green tea extract selectively activates peroxisome proliferator-activated receptor beta/delta in cultured cardiomyocytes. Br J Nutr. 2009 Jun;101(12):1736-9.
- Shen W, Hao J, Tian C, Ren J, Yang L, Li X, Luo C, Cotma CW, Liu J. A combination of nutriments improves mitochondrial biogenesis and function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. PLoS One. 2008 Jun 4;3(6).