Monthly Archives: April 2014

The Role of the Gut Microbiome

Closeup of woman with hands on her stomach

Deoxyribonucleic acid (DNA), the blueprint for life, is contained in every cell of the human body and every living organism for that matter. Everything about you—from the color of your hair to the hand you write with—comes from tightly coiled helical structures inside your cells. That’s pretty amazing right! For a long time, however, we were taught that DNA was fixed. If you struggled to lose weight, you would blame it on bad genes. But new discoveries have shown us that DNA is not our destiny.

After the Human Genome Project, scientists and clinicians were able to use a trove of tools and technologies to explore how genes affect complex diseases. Based on various biomedical studies, researchers have developed sophisticated diagnostic tools to identify a patients’ risk for diseases, such as diabetes, cardiovascular disease, and cancer.  Taking it one step further researchers are designing more sophisticated treatment modalities that target the genes involved in diseases.

If DNA is fixed, you’d be right to wonder how new treatments can change DNA. Truth is DNA is only part of the story of how you become, well, you. The epigenome helps to explain the rest of the story. Epigenome refers to the layer of specialized chemical tags that lie above the DNA-histone complex (DNA wraps itself around histones so it can fit inside of cells.) The epigenetic tags shape the structure of the genome. Epigenetic tags can tighten or relax genes, which turns genes on or off. What determines whether epigenetic tags are turning genes on or off? The environment, nutrition, and lifestyle choices all affect the epigenome. In essence, the epigenome is the middleman between the external environment and our genes. Biomedical research drives us closer to understanding how the environment and genetics plays a role in our health. At the same time, scientists are exploring how microorganisms inhabit the human body influences health.

In the United States, the Human Microbiome Project is one of many international efforts geared toward studying microbial communities that reside in various organs in the body, such as the lung, urogenital tract, and gut. The human microbiome consist of a collection of organisms that are much smaller than our cells, yet they make up 99% of the body’s total genetic information—outnumbering human cells ten to one. So it makes sense that the expansive microbial genome plays an essential role in health and disease.

Anyone who has gone to the dentist because of tooth decay, gingivitis, or periodontal disease, for example, has experienced the effects of microbial imbalances. The overgrowth of nasty bacteria in plaque in the mouth eats away at protective teeth enamel. And if it is not caught in time it progresses beyond just the tooth enamel and works into the gums. Bacteria and inflammation eventually destroys the gums and the supportive tissues that keep teeth firmly seated in their sockets. Taking things one step further, oral bacteria has long been associated to cardiovascular disease. Various studies have also linked microbial flora in the lungs to respiratory disease, type 2 diabetes, and irritable bowel syndrome. Researchers found that gut microbes differed between lean and overweight individuals. In particular, the microbial communities in obese individuals produced proinflammatory molecules and a toxin called lipopolysaccharide (LPS), which promotes chronic inflammation and triggers insulin and leptin resistance to cause weight gain.

Is the Microbiome Fixed or Flexible?

It is definitely flexible! Like human DNA, the microbial DNA is inherited too. Infants pick up their microbiome as they pass through the birthing canal. A mother’s vaginal microbiota is composed of healthy bacteria. Cesarean sections, unfortunately, do not afford children the same beneficial microbiome as a vaginal birth. Furthermore, a cesarean delivery has been associated with childhood obesity, as well as an increased risk for asthma, eczema, and type II diabetes. So if possible it is better to opt for a vaginal delivery.

But just as the epigenome allows DNA to be modified, the microbial genome can be influenced by environmental factors, such as the environment and diet. While more work is needed to understand the effects of microbiome on human health, data shows that microbes are readily transferable from person to person and person to environment. Which is a good thing because it means that our microbial genome is not fixed and they are in fact things that we can do to enhance the microbial environment in our bodies to promote health not disease. Here are a few tips:

  • Drink plenty of water because it keeps your digestive system healthy.
  • Consume foods that are high in fiber, which helps digestion run smoothly and prevents constipation.
  • Go for a walk or engage in some form of physical activity. Incorporate physical activity into your daily routine because it speeds up digestion by increasing blood flow and tightening up muscles involved in digestion.
  • Boost good gut bacteria with foods that contain healthy bacteria, such as yogurt and kefir, or probiotic supplements.

Much like the epigenome, the microbial communities can be modified through diet lifestyle changes.

Omega-3 Fats Targets Inflammation in Alzheimer’s Disease

Omega-3 Supplements and Fish

Alzheimer’s disease (AD) is the sixth cause of deaths in United States. It is a debilitating, irreversible, progressive neurodegenerative disease that develops mainly in older adults (a rare type that has a genetic component may develop in people as young as 30 years old). Alzheimer’s disease slowly affects cognitive functioning from early signs such as forgetfulness to more progress of signs, such as being unable to carry out any activities of daily living without the help of others.

It is a complex brain disease, and the etiology remains largely a mystery; however, we know that the environment, genetics, and lifestyle factors have all been implicated as risk factors in Alzheimer’s disease. Amyloid-beta plaques in the brain, however, are the hallmark sign of AD. The plaques are formed because of the buildup of amyloid beta proteins that destroy brain cells. You may be wondering why these plaques are allowed to form in the first place. The body should have a cleanup crew to remove harmful molecules.  And, in fact, it does! When tissue injury occurs, an acute inflammatory process recruits mediators, which responds to the localized tissue problem and gobbles up abnormal cells. Then specialized cells enter the area to remove the debris left after an inflammatory response—a step called the resolution pathway. This pathway consists of various classes of mediators involved in removing dead tissue, as well as molecules involved in inflammation. A recent study demonstrates that, in Alzheimer’s disease, this resolution pathway becomes dysfunctional.

Karolinska Institute researchers conducted a study in which they analyzed cerebrospinal fluid (CSF) of 15 Alzheimer’s patients, 20 individuals with mild cognitive impairment (MCI), and 21 control subjects; they also examined the postmortem hippocampal brain tissue of 10 Alzheimer’s patients and 10 control subjects.1

The researchers were attempting to identify specialized pro-resolving mediators (SPMs) as well as their receptors to determine if the resolution process of inflammation is downregulated in Alzheimer’s disease patients. The results show mediators associated with the resolution pathway (i.e., SPMs and SPM receptors) were found in the brain, which indicate that the brain is equipped with the capacity to restore itself post-inflammation. They also found that levels of a specific resolution pathway mediator was reduced in the CSF and postmortem brain tissue of AD patients—suggesting that the resolution process in the brain becomes dysfunctional in Alzheimer’s disease.

The study offers exciting, new insights into novel therapies that can target pathways to prevent and treat Alzheimer’s disease. When studies such as this are published, researchers work toward developing and testing potential therapies that pinpoint the mechanism involved, in this case treatments would be targeting the resolution pathway. One way would be to stimulate the pathway by developing studies in which SPM treatments are used; another option would be to explore the effects of omega-3 fatty acid supplementation on the SPM pathway.

Omega-3 fatty acid derivatives have been shown to stimulate the resolution process of inflammation. Besides being a healthy fat that has been shown to reduce inflammation, omega-3 fatty acids have been shown to reduce the risk for various diseases such as cancer, arthritis, and heart disease. Omega-3s are highly concentrated in the brain and appeared to play a role in memory, cognition, and behavior—three areas that are significantly affected in Alzheimer’s disease.

Inflammation can be linked to practically every disease process. Omega-3 fatty acids work to reduce inflammation and trigger the resolution pathway.  Coldwater fish, such as mackerel and salmon, are a good source of omega-3 fatty acids. Other sources of omega-3 fatty acids include krill and algae. If you choose to use omega-3 fatty acid supplements, look for pharmaceutical-grade products that are free of heavy metals.

Reference:

1.         Wang X, Zhu M, Hjorth E, et al. Resolution of inflammation is altered in Alzheimer’s disease. Alzheimer’s & dementia : the Journal of the Alzheimer’s Association. 2014.

Irisin: An Exercise Hormone Linked to Healthy Aging

Senior Woman Lifting Dumbbells

Wrinkles, age spots, and crow’s feet are just some of the physical signs of aging. Aging, however, isn’t skin deep; it goes deeper than what you see when you look in the mirror. On a molecular level, a cell’s days are numbered from the moment it’s made. Every cell in the human body undergoes a finite number of replication cycles. In the intricate process of cellular replication, DNA is condensed into 23-paired chromosomes. The majority of DNA is found within the nucleus, which is involved in regulating cell growth and reproduction. Telomeres cap the ends of chromosomes. These terminal caps prevent the ends of chromosomes from fraying and sticking together.

Telomeres have a finite lifespan. As a cell divides, telomeres shorten. Normally, cells can divide anywhere between 50 to 70 times. And with each replication, telomere length is lost. The telomere gene sequence is inconsequential, so important genetic information is not lost. Rather, telomeres serve to initiate cellular senescence. Once telomeres reach a point in which they are critically short, the cell is marked to undergo apoptosis—cell death.

Did you know the mitochondria contains DNA? The mitochondria are energy warehouses within cells. Each mitochondrion has a small amount of DNA called mitochondrial DNA (mtDNA). Just like nuclear DNA, mtDNA is capped with telomeres. Aging is a complex process that involves many pathways. Mitochondrial DNA has been strongly associated with the aging process. Although advanced aging is a complex issue, telomere dysfunction has been implicated as a major contributing factor.1,2

Under normal circumstances, telomeres initiate cell death; the process ensures aging cells are removed to make space for newer, younger cells. When telomeres don’t function properly, health problems occur: shortened telomeres have been linked to age-associated diseases, such as Alzheimer’s disease and cancer. In a research study, endothelial cells were exposed to either an organic peroxide (free radical molecule) or a glutathione inhibitor (antioxidant-blocking molecule).3 Under oxidative stress, the telomeres became shorter over a faster period of time, which prompted premature cell death.

To further elucidate the association between advanced aging and inadequate telomere activity, scientists conducted a study in which they explore the effects of a newly discovered exercise hormone and aging.4 Irisin is a hormone that is released by muscles after exercise. The hormone’s activity mimics healthy caloric restriction—both of which promote fat-burning activity. In the study, 81 healthy, non-obese participants were asked to refrain from physical activity (short-term, not long-term exercise influences irisin levels) for 12 hours. The scientists found that irisin levels were higher among individuals who had longer telomeres compared to those with shorter telomeres. These findings further support the notion that telomere integrity plays a crucial role in healthy aging. The study demonstrates that physical activity promotes weight loss, which reduces the risk for type 2 diabetes, obesity, metabolic syndrome, heart disease, and cancer.

Understanding how telomeres and irisin may contribute to disease offers scientists insight into novel therapies that can target diseases.  For the everyday person, this study shows the importance of staying active on a daily basis to help promote healthy aging—because youth and vitality starts from within.

References:

1.         He Y-H, Lu X, Wu H, et al. Mitochondrial DNA content contributes to healthy aging in Chinese: a study from nonagenarians and centenarians. Neurobiology of aging. 2014.
2.         Sahin E, Colla S, Liesa M, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 2011;470(7334):359-365.
3.         Kurz DJ, Decary S, Hong Y, Trivier E, Akhmedov A, Erusalimsky JD. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. Journal of cell science. 2004;117(11):2417-2426.
4.         Rana KS, Arif M, Hill EJ, et al. Plasma irisin levels predict telomere length in healthy adults. AGE. 2014:1-7.