How to reverse degenerative diseases
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.
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