This is a new day!: 2013

Wednesday, October 30, 2013

What Are Telomeres And How Do They Affect Heart Disease?

Heart ailments and telomeres

Heart ailments have become a very common disabling condition while the cure of heart related diseases is quite costly and it affects a large section of the human population. The heart treatment expenditure in the USA is nearly $35 billion. Cardiovascular diseases (CVD) are highly associated with age and cases of heart failure are common in the aged population. Characterization of heart disease samples have found increased levels of apoptosed myocytes and attrition of the telomere. Interventions aimed at improving the length of telomeres can be an effective mode of preventing cardiovascular diseases.

Telomere and cardiovascular diseases

The dysfunctioning of telomere has been reportedly the most important reason behind cardiac failures as is evident from animal studies as well as human heart samples. Telomere shortening in animal models has showed inhibition to proliferation of myocytes coupled with myocyte hypertrophy and an enhanced rate of apoptosis. Cardiovascular diseased patients show 40% reduction in their telomere lengths when compared with the healthy normal human beings and that the shorter the length of the telomere, more is the disease severity. In addition, shortened telomeres were linked to reduction in renal function. Higher lengths of telomere are responsible for an increase of 5% ejection by the left ventricle. In the aged population the variation in the ejection capability is highly dependent on the telomere length. Also in the same population, heart related ailments show characteristics of moderate to low dilation and hypertrophy with an overall increment in the cell death. The cells exhibiting the characteristics followed the p16INK4a path and presented shorter telomeres. Besides, the patients with heart diseases and shortened telomeres have the risk of being anemic with compromised prognosis. In a study carried out by the New York Heart Association, it was observed that short telomere containing patients with heart failure (Class II-IV) were more at risk of death within a period of about 18 months. Therefore, shortened telomere lengths might be used as successful predictors of death in chronic cardiovascular diseased patients.

Cardiovascular diseases and telomerase dysfunction

Although, it is now well known that the length of the telomeres has a big impact in cardiovascular disease development and progression, there is very little knowledge regarding the dysfunctioning of telomerase in the aforesaid process. There are some studies which suggest an improvement in the infarct area associated with cardiac myocytes that followed a ligation of the coronary artery promoting better survival rates after an introduction of human telomerase reverse transcriptase (hTERT). In addition, the TERT transduced animal models are highly resistant to ischemic injuries to brain. Alternatively, it was also observed that TERT deficiency results in increased susceptibility to oxidation induced stress and stroke development. According to the work of Werner et al., an increase in physical exercises results in enhanced telomerase activity and decrease in chances of heart disease. It is noteworthy to mention that under conditions of telomerase absence, the expression of proteins that stabilize telomeres are severely hampered which presents more critical case of cardiac apoptosis. Recently, the study by Perez-Rivero and his group provided a direct linkage between hypertension and the activity of telomerase. TERC-/- models showed a much higher expression of endothelin converting enzyme thereby developing hypertension. Moreover, studies with the patients suffering from hypertrophy that involved the progenitor cells showed very low activity of telomerase and rapid rates of senescence. Also, the TERC-/- condition leads to decrease in angiogenic capacity as compared to the wild type form. They also suffer from hypertrophy of myocytes, change in the structure of the heart and failure of left ventricle. Epel et al., carried out a landmark study in 62 volunteers wherein they found that reduced activity of telomerase was linked to a number of cardiovascular disease risk factors. Among those highly implicated are smoking, fasting glucose levels, high blood pressure and a bad lipid profile. But no association could be found between the various factors and length of telomere. The study proposed that the reduced telomerase can be used as a marker of cardiovascular diseases that precedes the shorter lengthed telomeres.

The available data suggest that individuals with short lengthed telomeres are at high risks of catching with cardiovascular diseases. The increase in activity of telomerase can provide the necessary relief under such circumstances. It has been found that a regulated diet and good healthy habits can be helpful only to a limited extent. However, there are supplements present that can rejuvenate the telomerase and lead to their activation. Such activator molecules can be easy to use and without any side effects providing the beneficial effects by modulating the existing regulators within the body which otherwise had ceased to function. Human beings are continuously exposed to oxidative agents that can interfere with the functioning of the telomerases. Therefore, the intake of supplements that possess anti-oxidative properties can reverse the telomerase inhibition and promote human health.

Nathan W Pace is a Health Educator, Personal Success Life Coach, Social Marketer, Entrepreneur – Empowering individuals through life transitions by overcoming roadblocks.

Learn more about supplements that activate Telomerase in the aid of short Telomeres at http://youthfulsupplement.com

Wednesday, October 23, 2013

Can You Use Supplements To Reverse Degenerative Diseases?

Telomerase and age reversal

One of the critical questions about human health nowadays has to do with the question of telomere length and how malleable it is. The length of the telomere at any point in life has been a faithful predictor of the various diseased states in humans. The role of the telomere length shortening and telomerase dysfunction has now been well established factors in the acceleration and regulation of human aging and related disorders. The telomere shortening has behind it a number of causal factors which include prenatal exposure to adversities or stress, genetic disorders and several environmental cues like lifestyle associated habits of smoking and present day stressful conditions. Therefore, if these factors are intervened, the aging process can be prolonged. Also, the interception at the level of telomerase activation can aid in the lengthening of telomeres thereby leading to reversal of aging and promoting youthful, healthy aging.

Telomere length and aging

According to general physiological process, the length of the telomere decreases with each cell cycle and that leads to aging. According to some estimates, the rate of decrement of telomere length takes place at an alarming pace of ~ (25-28) bp with each passing year. The accelerated rate of telomere shortening for certain group of individuals under study showed enhanced levels of age associated disease incidences with overall reduced lifespan. As is evident, telomere shortening is affected by a plethora of epigenetic, genetic and environmental factors as well as the lifestyle of the individual in question. However, the telomere erosion was not gender biased. As the length of the telomere goes below a critical level, the cells undergo apoptotic death. The lifestyle of the human beings has a big role to play in the acceleration or deceleration of the shortening of telomeres. Some of the lifestyle issues under the glare are an inactive daily routine with lack of exercises, smoking, obesity, intake of diet considered unhealthy. Each of these factors has been highly implicated with shortened telomeres that results to disease manifestations and a premature death. The acceleration in the telomere attrition has also been associated with the onset of many age related health disorders in humans like diabetes, neurodegenerative diseases, heart failure, osteoporosis and tumorigenesis. An evaluation of the telomere lengths in the elderly population indicates that the ones with shortened telomeres are more at risk of mortality than the ones with longer telomeres. An enhanced rate of telomere erosion affects the lifespan and health of human beings at many levels. Shortened telomeres give rise to the instability of the genome causing fusion of chromosomes leading to cancer development. Interfering with the shortening of telomere lengths through the activation of telomerase activity can lead to reversal of the aging process.

Knowledge about telomerase

Besides, the several factors involved in the regulation of telomere length and related developments of aging associated disorders, the reverse transcriptase, telomerase is undoubtedly the main player behind the maintenance of telomere length. The human telomerase enzyme is composed of subunits of hTERT (the catalytic unit) and hRT (RNA part). There are also additional accessory proteins that help in its formation and functioning. The proteins like NHP2, NOp10 and Dyskerin help in the stabilization as also the accumulation of the hTR subunit. In addition chromatin remodeling factors are responsible in its epigenetic regulation.

Modulation of telomerase activity

The knowledge about the regulation of telomerase activity becomes an absolute necessity in the light of its significant role in telomere length maintenance. Like the telomere length, telomerase enzyme has been found to be regulated at the epigenetic, genetic and environmental levels. The genes that are associated with the telomeres remain highly conserved across species and they show very little variability in humans. A whole lot of experimental data are establishing the epigenetic modifications like methylation, acetylation to be quite crucial in the regulation of telomerase. In addition, modulations like translocation to the nucleus or phosphorylation are important to control the activity of telomerase. The pathways like PI3K or AKT have also been found in the regulation of the enzyme’s expression and activities. Previously, it was thought that the telomerases were silent transcriptionally. But that notion is now being challenged by a very recent work. The telomeric repeat containing RNA (TERRA) has been the latest addition to the expanding repertoire of the telomerase enzyme complex. Without going into the details of the work, it can be said that there exists an inverse correlationship between the activity of telomerase and TERRA. According to the recent studies it has been proposed that TERRA has important roles to play in telomerase regulation through the maintenance of enhanced telomere structures and helping to carry out many important functions of telomeres.

Intervention to increase telomerase activity and reverse aging

In the past decade or so, there has been rapid progress in the field of medical sciences and as a result an increasing number of aged individuals are being added to the world population. Therefore, the current focus of the scientific world is to strive for regenerative therapies that can slow down or reverse aging and prevent the accelerated decline in human health. The crucial question that remains to be answered is that how effective this age reversal can be. Since the discovery of telomerase in the early 1980s, it has been rapidly reputed as a facilitator of youth. With the progress of cell division the telomeres decline and undergo attrition, the main reason behind aging. The telomerases can interfere with the rate of the telomere shortening in many different cell types that include even the stem cells. The telomerase can lengthen the telomeres and hence the basic idea is to activate the enzyme in order to slow down the process of aging. Recently, the activation of telomerase was found with the introduction of hTERT in animal models. The hTERT based gene therapy resulted in extended longevity. Although such models have yielded successful results and there are on going clinical trials with their use in humans, there remain significant apprehensions regarding their use as hTERT is a well known promoter of cancer. Also, the other side effects for their use could also not be ruled out and there needs to be sufficient research before putting them into regular use in the humans. Therefore, the natural activators of telomerase can be a useful and safe choice for the reversal of age and promoting youthful aging. There are enough evidences to suggest that besides being effective these activators of telomerase activity are also quite safe. There is no report of side effects for them also. Besides, the scientists are of the opinion that these natural compounds used as dietary supplements or separately can be effective anti-oxidant agents that can slow down aging with little chances of incurring cancer. Infact many are of the opinion that if used judiciously they can inhibit cancer by the prevention of DNA damage that happens with telomere erosion. Nonetheless, the activation of telomerase can be an effective area to exploit for the reversal of aging.

Nathan W Pace is a Health Educator, Personal Success Life Coach, Social Marketer, and Entrepreneur who empowers individuals through life transitions by overcoming roadblocks.

Learn more about supplements that activate Telomerase to lengthen Telomeres at http://youthfulsupplement.com

Friday, October 18, 2013

Can Daily Stress Cause You To Age Faster?

The genetic information of all organisms is contained within the chromosomes making them the source of our organizational patterns like color, health, behavior and so on. Each chromosome in our body is buffered by the presence of structures at either of its ends made of protein-DNA complexes called telomeres. These telomeres protect the genome from being degraded nucleolytically; prevent them from getting fused with other chromosomes or recombination processes. In general terms, they protect the genome from undue erosion. The telomeres are therefore key to the preservation of our genetic code and cannot be done away with. According to the normal physiological process, in each cellular division a little portion of DNA from the telomeres is lost as well. Beyond a threshold point of the telomeric length, the cells undergo orchestrated death through apoptosis. The length of the telomere therefore may act as an indicator that determines the cell or organism lifespan. Various agents that we encounter through our lifestyle might induce the shortening of the telomeres. These agents could cause damage to the DNA or directly affects the telomeres thereby modulating the general health and/or the lifespan of the individual. Therefore, there are factors that can accelerate the telomere shortening and interfere with healthy life and aging. Efforts are now being focused on decelerating this process and reverse the associated phenomenon of aging and related disorders.

Variability of the telomere length

Although the general notion is that the telomere length varies according to the age of the individual, there are high degrees of variability of the telomere length even among individuals of similar age. Existing reports suggest that the telomere length is determined genetically and that inheritance accounts for this variation in (40-80) % of the cases. According to the work of Okuda and his group it was observed that the lengths of telomeres from the DNA samples of neonatal showed significant synchronization that were isolated from umbilical artery, WBCs and skin. However, this was not the case with the telomere lengths of different newborns which seemed to vary to a great extent. The synchronization that was observed within the tissues of neonatals are lost and become more heterogenous in the aged individuals. There are also literatures available which suggest that the length of the telomere varies between people from different ethnic background. The telomere lengths in African Americans are longer than those of the Caucasians while no significant difference between the telomere lengths was observed from the newborns of the two races. It was also significant that the adult women possess longer telomeres than their male counterparts. Women also show a slower rate of shortening of the telomere. A cue to this may be found from the study that estrogen stimulates telomerase activity. Significant association between estrogen levels and the activity of telomerase have been established. Misiti et al. have proposed that estrogen is also effective in up-regulating the gene expression of telomerase besides its activity.

Stress can affect telomeres

Besides the genetic factors in the determination of telomere length, exposure to varied environmental factors has a significant role to play in it. The telomeres due to their genetic make up show a high degree of sensitivity to oxidation induced stress. Such is the impact of the oxidative stress on telomere length that it has now been accepted that it causes greater damage to telomeres than even the cell division process. Increase in lifestyle related psychological stress enhances oxidative stress that results in decreased telomerase activity and accelerated telomere attrition. Studies have revealed that the exposure to stress for longer duration of time can result in the reduced activity of telomerase that in turn fastens telomere shortening in cells of both endothelial or smooth muscle origin. Accordingly, it has been demonstrated that the intake of anti-oxidants causes the enhancement in telomerase activity with a concomitant decreased telomere shortening. An increase in the level of LDL oxidation has been linked to the leucocytes with shorter lengthed telomeres stiffening the artery.

Other environmental factors and length of telomeres

Evidences have been put forward that suggest that inflammation contributes to a large extent in the shortening of telomeres in immune system cells via the promotion of leucocytes. The telomere length has been negatively affected by the increase in the levels of some cytokines like C-reactive protein (CRP) and IL-6. It has even been observed that mistreatment during childhood, illness of chronic nature and adverse events of life are linked to the formation of short telomeres at an early age. Smoking results in an increase in the inflammatory responses through oxidative stress and a subsequent shorter lengthed telomere. Female smokers are more at risk of eroding the telomeres early. Smoking stimulates the telomere shortening according to a concentration gradient; more the smoking, more is the shortening of telomere. Good habits of physical exercises relates to improvements in telomeres in adults as also in the adolescents thereby suggesting its association with anti-aging process. Intake of marine foods rich in ω-fatty acids also positively influences telomeres. Cherkas and colleagues recently added to this growing list and stated that the socioeconomic status of the individuals can have an impact on the length of telomeres.

Mechanisms to lengthen telomeres

The main function of the telomeres is to support DNA erosion from the ends of chromosomes during replication thereby buffering the process. The enzymes involved in the replication process (DNA polymerases) are unable to copy the entire template as a result with each cell cycle a length of the chromosomal end is not copied and is lost forever. However, in order to prevent this incomplete genome replication and DNA loss, the organisms have evolved different mechanisms. The majority of the organisms make use of the retro-transcriptase, telomerase to lengthen their telomeres. However, it has been found that organisms that are deficient in telomerase activity have devised other alternatives to protect and lengthen their telomeres by processes known as Alternative lengthening of Telomere (ALT). In some organisms, the RecQ helicase is required for ALT. In addition, the removal of Mismatch Repair Pathway can cause an increase in ALT process. Therefore the telomere length is crucial in maintenance of our health and lifespan. On the other hand, the telomerase activity is absolutely necessary to lengthen the telomeres and keep us healthy and prolong our lives. With our lifestyle we expose ourselves to increased levels of oxidative stress that interferes with telomerase activity and accelerates telomere shortening. Therefore, the intake of supplements that can stimulate the telomerase activity can be quite beneficial in maintaining our health and acting as anti-aging factors. The administration of anti-oxidants could help in this regard by enhancing the activity of the telomerase which in part explains their effectiveness as age reversing agents.

Nathan W Pace is a Health Educator, Personal Success Life Coach, Social Marketer, and Entrepreneur who empowers individuals through life transitions by overcoming roadblocks.

Learn more about supplements that activate Telomerase to lengthen Telomeres at http://youthfulsupplement.comhttp://youthfulsupplement.com