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

2015 ◽  
Vol 5 (1) ◽  
pp. 11
Author(s):  
Tommy Rodriguez
Keyword(s):  
Transmembrane Protein ◽  
Genetic Regulation ◽  
Comparative Sequence Analysis ◽  
Biological Aging ◽  
Altered State ◽  
Telomere Attrition ◽  
Related Disease ◽  
Age Related ◽  
Evolutionary Context ◽  
Klotho Protein

<p class="1Body">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 a-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.</p>

scholarly journals Systematic Review of Studies on Telomere Lengths in Patients with Multiple Sclerosis

2020 ◽  
Author(s):  
Jan Bühring ◽  
Michael Hecker ◽  
Brit Fitzner ◽  
Uwe Klaus Zettl
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Individual Variability ◽  
Biological Aging ◽  
Specific Cell ◽  
List Type ◽  
Healthy Controls ◽  
Telomere Attrition ◽  
Related Disease ◽  
Age Related

AbstractBACKGROUNDTelomeres are protective cap structures at the end of chromosomes that are essential for maintening genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases.OBJECTIVEWe aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS).METHODSA comprehensive literature search was conducted to identify original studies that presented data on TL in samples from MS patients. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies.RESULTSA total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in MS patients were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes.CONCLUSIONSDespite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the pathomechanisms of MS.HighlightsThe relationship between aging and the pathophysiology and course of MS is not fully understoodWe have identified seven studies that analyzed telomere lengths (TL) in patients with MSOur meta-analysis revealed significantly shorter leukocyte TL in MS patients compared to healthy controlsThere is evidence that individual variability in biological aging reflects clinical heterogeneity in MSThe potential use of TL as a biomarker of age-related disease mechanisms deserves further investigation

Downregulation of Klotho expression by dehydration

2011 ◽  
Vol 301 (4) ◽  
pp. F745-F750 ◽  
Author(s):  
Cai Tang ◽  
Ganesh Pathare ◽  
Diana Michael ◽  
Abul Fajol ◽  
Melanie Eichenmüller ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Accelerated Aging ◽  
Early Death ◽  
Renal Tissue ◽  
Hek293 Cells ◽  
Protein Abundance ◽  
Transcript Levels ◽  
Age Related ◽  
Klotho Protein ◽  
Growth Deficit

Klotho, a transmembrane protein, protease, and hormone mainly expressed in renal tissue counteracts aging. Overexpression of Klotho substantially prolongs the life span. Klotho deficiency leads to excessive formation of 1,25(OH)2D3, growth deficit, accelerated aging, and early death. Aging is frequently paralleled by dehydration, which is considered to accelerate the development of age-related disorders. The present study explored the possibility that dehydration influences Klotho expression. Klotho transcript levels were determined by RT-PCR, and Klotho protein abundance was detected by Western blotting in renal tissue from hydrated and 36-h-dehydrated mice as well as in human embryonic kidney (HEK293) cells. Dehydration was followed by a significant decline of renal Klotho transcript levels and protein abundance, accompanied by an increase in plasma osmolarity as well as plasma ADH, aldosterone, and 1,25(OH)2D3 levels. Antidiuretic hormone (ADH; 50 nM) and aldosterone (1 μM) significantly decreased Klotho transcription and protein expression in HEK293 cells. In conclusion, the present observations disclose a powerful effect of dehydration on Klotho expression, an effect at least partially mediated by enhanced release of ADH and aldosterone.

scholarly journals Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 660
Author(s):  
Mengdi Yu ◽  
Hongxia Zhang ◽  
Brian Wang ◽  
Yinuo Zhang ◽  
Xiaoying Zheng ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Adenosine Monophosphate ◽  
Sirtuin 1 ◽  
Public Health Issue ◽  
Biological Aging ◽  
Related Disease ◽  
Age Related ◽  
General Decline

Aging is a fundamental biological process accompanied by a general decline in tissue function. Indeed, as the lifespan increases, age-related dysfunction, such as cognitive impairment or dementia, will become a growing public health issue. Aging is also a great risk factor for many age-related diseases. Nowadays, people want not only to live longer but also healthier. Therefore, there is a critical need in understanding the underlying cellular and molecular mechanisms regulating aging that will allow us to modify the aging process for healthy aging and alleviate age-related disease. Here, we reviewed the recent breakthroughs in the mechanistic understanding of biological aging, focusing on the adenosine monophosphate-activated kinase (AMPK), Sirtuin 1 (SIRT1) and mammalian target of rapamycin (mTOR) pathways, which are currently considered critical for aging. We also discussed how these proteins and pathways may potentially interact with each other to regulate aging. We further described how the knowledge of these pathways may lead to new interventions for antiaging and against age-related disease.

scholarly journals Metabolic alterations caused by the mutation and overexpression of the Tmem135 gene

2020 ◽  
Vol 245 (17) ◽  
pp. 1571-1583 ◽  
Author(s):  
Wei-Hua Lee ◽  
Vijesh J Bhute ◽  
Hitoshi Higuchi ◽  
Sakae Ikeda ◽  
Sean P Palecek ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Transmembrane Protein ◽  
Retinal Pigment ◽  
Cellular Metabolism ◽  
Metabolic Changes ◽  
Resonance Spectroscopy ◽  
Rpe Cells ◽  
Metabolic Alterations ◽  
Related Disease ◽  
Age Related

Mitochondria are dynamic organelles that undergo fission and fusion. While they are essential for cellular metabolism, the effect of dysregulated mitochondrial dynamics on cellular metabolism is not fully understood. We previously found that transmembrane protein 135 ( Tmem135) plays a role in the regulation of mitochondrial dynamics in mice. Mice homozygous for a Tmem135 mutation ( Tmem135FUN025/FUN025) display accelerated aging and age-related disease pathologies in the retina including the retinal pigment epithelium (RPE). We also generated a transgenic mouse line globally overexpressing the Tmem135 gene ( Tmem135 TG). In several tissues and cells that we studied such as the retina, heart, and fibroblast cells, we observed that the Tmem135 mutation causes elongated mitochondria, while overexpression of Tmem135 results in fragmented mitochondria. To investigate how abnormal mitochondrial dynamics affect metabolic signatures of tissues and cells, we identified metabolic changes in primary RPE cell cultures as well as heart, cerebellum, and hippocampus isolated from Tmem135FUN025/FUN025 mice (fusion > fission) and Tmem135 TG mice (fusion < fission) using nuclear magnetic resonance spectroscopy. Metabolomics analysis revealed a tissue-dependent response to Tmem135 alterations, whereby significant metabolic changes were observed in the heart of both Tmem135 mutant and TG mice as compared to wild-type, while negligible effects were observed in the cerebellum and hippocampus. We also observed changes in Tmem135FUN025/FUN025 and Tmem135 TG RPE cells associated with osmosis and glucose and phospholipid metabolism. We observed depletion of NAD+ in both Tmem135FUN025/FUN025 and Tmem135 TG RPE cells, indicating that imbalance in mitochondrial dynamics to both directions lowers the cellular NAD+ level. Metabolic changes identified in this study might be associated with imbalanced mitochondrial dynamics in heart tissue and RPE cells which can likely lead to functional abnormalities. Impact statement Mitochondria are dynamic organelles undergoing fission and fusion. Proper regulation of this process is important for healthy aging process, as aberrant mitochondrial dynamics are associated with several age-related diseases/pathologies. However, it is not well understood how imbalanced mitochondrial dynamics may lead to those diseases and pathologies. Here, we aimed to determine metabolic alterations in tissues and cells from mouse models with over-fused (fusion > fission) and over-fragmented (fusion < fission) mitochondria that display age-related disease pathologies. Our results indicated tissue-dependent sensitivity to these mitochondrial changes, and metabolic pathways likely affected by aberrant mitochondrial dynamics. This study provides new insights into how dysregulated mitochondrial dynamics could lead to functional abnormalities of tissues and cells.

scholarly journals In vivo Pooled Screening: A Scalable Tool to Study the Complexity of Aging and Age-Related Disease

2021 ◽  
Vol 2 ◽  
Author(s):  
Martin Borch Jensen ◽  
Adam Marblestone
Keyword(s):  
Biological Aging ◽  
Living Animal ◽  
Related Disease ◽  
Open Questions ◽  
Age Related ◽  
Cellular Mediators ◽  
Direct Administration ◽  
Shed Light ◽  
Systemic Signals

Biological aging, and the diseases of aging, occur in a complex in vivo environment, driven by multiple interacting processes. A convergence of recently developed technologies has enabled in vivo pooled screening: direct administration of a library of different perturbations to a living animal, with a subsequent readout that distinguishes the identity of each perturbation and its effect on individual cells within the animal. Such screens hold promise for efficiently applying functional genomics to aging processes in the full richness of the in vivo setting. In this review, we describe the technologies behind in vivo pooled screening, including a range of options for delivery, perturbation and readout methods, and outline their potential application to aging and age-related disease. We then suggest how in vivo pooled screening, together with emerging innovations in each of its technological underpinnings, could be extended to shed light on key open questions in aging biology, including the mechanisms and limits of epigenetic reprogramming and identifying cellular mediators of systemic signals in aging.

scholarly journals Rescuing Immunosenescence via Non-Specific Vaccination

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 231-239
Author(s):  
Alexander I. Mosa
Keyword(s):  
Immune Responses ◽  
The Elderly ◽  
Short Review ◽  
Functional Markers ◽  
Healthy Life ◽  
Related Disease ◽  
Age Related ◽  
Population Vulnerability ◽  
Mechanistic Basis ◽  
Promising Avenue

Discrepancies in lifespan and healthy-life span are predisposing populations to an increasing burden of age-related disease. Accumulating evidence implicates aging of the immune system, termed immunosenescence, in the pathogenesis of multiple age-related diseases. Moreover, immune dysregulation in the elderly increases vulnerability to infection and dampens pathogen-specific immune responses following vaccination. The health challenges manifesting from these age related deficits have been dramatically exemplified by the current SARS-CoV-2 pandemic. Approaches to either attenuate or reverse functional markers of immunosenescence are therefore urgently needed. Recent evidence suggests systemic immunomodulation via non-specific vaccination with live-attenuated vaccines may be a promising avenue to at least reduce aged population vulnerability to viral infection. This short review describes current understanding of immunosenescence, the historical and mechanistic basis of vaccine-mediated immunomodulation, and the outstanding questions and challenges required for broad adoption.

scholarly journals Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease

Gerontology ◽  
2016 ◽  
Vol 63 (2) ◽  
pp. 103-117 ◽  
Author(s):  
Cia-Hin Lau ◽  
Yousin Suh
Keyword(s):  
Animal Models ◽  
Genetic Manipulation ◽  
Logic Gate ◽  
Therapeutic Interventions ◽  
Human Aging ◽  
Aging Research ◽  
Epigenome Editing ◽  
Related Disease ◽  
Age Related

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations.

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