Identifying Significant Biological Markers in Klotho Gene Variants Across Wide Ranging Taxonomy

Abstract

Biological aging is marked by progressively degenerative physiological change that causes damage to tissues and organs. Errors in biopolymers accumulate over time; mitochondrial dysfunction, telomere attrition, and wider genomic instability lead to an altered state of intercellular communication. In this investigation, my focus will be aimed at examining and identifying specifically critical biomarkers in genetic variants of KLOTHO (a transmembrane protein involved in the genetic regulation of age-related disease) among organisms with varied life spans that range across wide taxonomical rankings. Here, I investigate the correlation between lower and higher frequency α-amino acid compositions in Klotho protein factors within a grouped methodology; as to also include several demonstrative techniques in comparative sequence analysis for inferring relatedness in evolutionary context. Keywords: Klotho, KL gene, protein, protein evolution, comparative sequence analysis, multiple sequence alignment, Kalign, phylogenetc analysis, amino acid composition analysis IntroductionPromising new research in life extension has led to remarkable advancements in our basic understanding of the molecular mechanisms associated with aging. Within the last two decades, much of this research has focused on identifying potential genomic candidates for longevity, while seeking to explain how these individual genes can affect the biological process of aging. One of the proteins in particular (KLOTHO) has been the subject of several recently published papers. A handful of studies now suggest that genetic variants of KLOTHO [encoded by the KL gene] are associated with human aging and tumor suppression, and trials on model organisms involving KLOTHO variants has shown improvement in cognition and deceleration in age-related development (Dubal et al., 2014). In one such case, Dubal et al. (2014) demonstrated that systemic overexpression of Klotho variants in transgenic mice enhanced cognition and increased longevity by an average ratio of ±25 percent; whereas Klotho-deficient mice manifested a syndrome resembling accelerated human aging and displayed extensive and accelerated arteriosclerosis (Dubal et al., 2014).For reasons that are not yet fully understood, Klotho-associated mechanisms, "change cellular calcium homeostasis, by both increasing the expression and activity of TRPV5 and decreasing that of TRPC6 (Kurosu et al., 2005)." Moreover, altered mineral-ion homeostasis could be a cause of premature aging-like phenotypes (Kurosu et al., 2005). In order to gain a more comprehensive understanding of the underlying functions in molecular components of KLOTHO, we should begin by examining KL-derivative patterns across a wide evolutionary spectrum, without limiting ourselves to one individual taxa or another. Because the lifespan of organisms vary widely among species, a comparative approach could help us identify a set of unique signatures in the molecular variation patterns of KLOTHO. In turn, this may help provide meaningful referenc...

Sixteen weeks of aerobic training influence spirometry, s-klotho, and hemodynamic responses to sub-maximal exercise testing in obese men with severe obstructive sleep apnea

“…[18][19][20] On the other hand, aerobic exercise improves cardiorespiratory aspects of function in people with OSA. [21][22][23][24][25] The six Minute Walk Test (6MWT) is an exercise test that may be sub-maximal and/or maximal according to extent of effort on the participant's behalf. As part of the 6MWT the participant is instructed to achieve the greatest distance possible within 6minutes of walking.…”

The effects of partial sleep deprivation and the sub-maximal NDKS exercise testing protocol on S-Klotho and hemodynamic responses in women

“…19 The protein is associated with the degenerative process, acceleration of aging, bone lose, and alcohol consumption. [20][21][22][23][24] Furthermore, S-Klotho is a role-player in determining the sensitivity to insulin, mediating the binding of FGF19, FGF20, and FGR23 to their receptors as part of the growth process at the cellular level. 23 In addition, S-Klotho is suggested as a cardiovascular system "protector" via means of endothelium-derived NO production, 25,26 and has been proven to affect cellular calcium homeostasis via increased expression of TRPV5, and decreased TRPC6; and increases membrane expression of inward rectifier ROMK.…”

The effects of partial sleep deprivation and the maximal ndks exercise testing protocol on s-klotho, maximal oxygen uptake, and hemodynamic responses in young men

“…20,21 Without yet indicating the nature of the influence, the protein is associated with alcohol consumption, the degenerative process, bone lose, and acceleration of aging. [22][23][24][25][26] As part of the growth process at the cellular level, S-Klotho helps determine the sensitivity to insulin, via mediating the binding of FGF19, FGF20, and FGR23 to their receptors. 25 Via means of endothelium-derived Nitric Oxide production, S-Klotho protects the cardiovascular system, 27,28 decreased TRPC6 expression, increases TRPV5expression, increases membrane expression of inward rectifier ROMK affecting cellular calcium homeostasis.…”