Telomeres and Reversing Aging – Part 2

Inflammation is the underlying cause to the aging process. As we age, our immune system produces what is known as “low-grade” inflammation.

For many, inflammation is simply understood as a trajectory of biomarkers, for example the appearance of IL-6 or C-reactive protein (CRP), associated with a disease. However, inflammation is a very complex response to an injury, infection, or other stimulus, in which many different cells types and secreted factors orchestrate protective immunity, tissue repair, and resolution of tissue damage. Whereas acute inflammation limits tissue damage and resolves, chronic prolongation of the inflammatory state leads to progressive tissue damage. A central question, then, is how do we describe and begin to understand the mild pro-inflammatory state of aging. Luigi Ferrucci (NIA, NIH)

Inflammation is correlated with Diabetes II, obesity and cardiovascular disease, several cancers, frail bones, etc. So, what is the connection to telomeres?

There are several considerations in relating telomere biology to aging. First, physiologically there is overlap between the shortest telomere length of young children and the longest telomeres of the elderly. Most telomere shortening occurs early in life, in association with growth, and when the rate of disease in general is low. The paradigmatic telomere syndrome of dyskeratosis congenita is not at all typical of progerias, inherited syndromes in which patients appear old and suffer diseases of aging such as premature atherosclerosis or dementia. Furthermore, the organ damage of dyskeratosis congenita is not very similar to normal aging of marrow, lungs, and liver. The marrow becomes mildly hypocellular in older individuals, but stem cell numbers may actually increase, and blood counts remain stable; and neither the liver nor lungs normally become fibrotic with advanced age, as they often do in dyskeratosis congenita patients. Although in adults, relatively short leukocyte telomeres have been associated with cardiovascular events—a common morbidity of the aging population—the clinical correlations have not been consistent, and may be related to overall reactive oxygen species exposure. Rodrigo Calado and Neal Young – The Scientist, May, 2012

Epigenetics and Inflammation

Epigenetic or phenotype modifications are done through gene expression. The most well known of these is DNA methylation. The methylation pathway is the super highway for inflammation.

Methylation is the process of adding a carbon and three hydrogen atoms to a molecule. Neurotransmitters and proteins get methylated. The body uses methylation to create T-cells to kill viruses, bacteria, and cancers. It is a series of over 100 reactions in the body that are responsible for production of dopamine, growth factors, and glutathione. Glutathione helps with removal of heavy metals. When methylation is impaired, B-cells will be high and you will have ongoing inflammation. Viruses create cytokine storms which also propogate inflammation. You simply cannot heal while you are inflamed. Once methylation is corrected, inflammation generally reduces.

Here is a graphic of how cigarette smoke impairs methylation:

DNA methylation is the most studied epigenetic modification, capable of controlling gene expression in the contexts of normal traits or diseases.

Healthy function of telomeres requires adequate methylation. The important point to understand is that an adequate supply of methyl donors is needed for telomeres to work properly, just like your car needs gasoline.

In Part 3 we will examine epigenetic factors to help fix methylation pathways as a key component to the aging process and the various testing options for methylation and other related diagnostics.

Genetics: The Milk Revolution

In the 1970s, archaeologist Peter Bogucki was excavating a Stone Age site in the fertile plains of central Poland when he came across an assortment of odd artefacts. The people who had lived there around 7,000 years ago were among central Europe’s first farmers, and they had left behind fragments of pottery dotted with tiny holes. It looked as though the coarse red clay had been baked while pierced with pieces of straw. More from nature.com.

Cortisol – Part 1 – Relationship to Stress

Cortisol is, in many ways, a perplexing hormone. A certain amount of cortisol is necessary for optimal health, but too much or too little can be unhealthy. During acute episodes of stress, more cortisol is released to help the body cope with physical or psychological stressors (Tomlinson 2004). Its primary functions in the body are:

-Regulation of blood glucose levels in the liver;
-Regulation of the immune system;
-Regulation of carbohydrate, protein and lipid metabolism.

Essentially, cortisol is regarded as an anti-inflammatory hormone, a blood glucose modulator, an immune-modifier, and an adaptation hormone (Chrousos 2000). Depending on diet, exercise, stress, and time of day, serum levels of cortisol can vary.

During healthy conditions, cortisol levels peak in the early morning hours (usually around 8AM) and dip to their lowest between midnight and 4AM. The complex process of cortisol biosynthesis and release is sensitive to disruption by both internal and external factors (Beishuizen 2001; Tomlinson 2004; Weerth 2003). In the face of chronic psychological stress, for example, the adrenal glands excrete an abnormal amount of cortisol in an abnormal rhythm.

Cortisol, being a catabolic hormone (a hormone that breaks down tissues), when out of balance and unregulated, can have detrimental effects on body composition. Moreover, too much cortisol can suppress the immune system, while too little can lead to autoimmunity and rheumatologic disorders (Chrousos 2000; Wu 2008; Muneer 2011; Sapolsky 2002; Tak 2011).

Cortisol receptors are expressed throughout the body, including in the brain; therefore, derangement of the biosynthesis, metabolism and release of cortisol can disrupt many physiologic systems (Beishuizen 2001).

Next week we will explore Cortisol and its relationship to weight.