scholarly journals Melatonin and Sirtuins in Buccal Epithelium: Potential Biomarkers of Aging and Age-Related Pathologies

2020 ◽  
Vol 21 (21) ◽  
pp. 8134
Author(s):  
Annalucia Carbone ◽  
Natalia Linkova ◽  
Victoria Polyakova ◽  
Ekaterina Mironova ◽  
Ulduz Hashimova ◽  
...  
Keyword(s):  
Aging Process ◽  
Expression Patterns ◽  
Invasive Procedure ◽  
Buccal Epithelium ◽  
Non Invasive ◽  
Biomarkers Of Aging ◽  
Expression Of Genes ◽  
Age Related ◽  
Invasive Method ◽  
Immunofluorescence Intensity

Melatonin (MT) and sirtuins (SIRT) are geroprotective molecules that hold back the aging process and the development of age-related diseases, including cardiovascular pathologies. Buccal epithelium (BE) sampling is a non-invasive procedure, yielding highly informative material for evaluating the expression of genes and proteins as well as the synthesis of molecules. Among these, MT and SIRTs are valuable markers of the aging process and age-related pathologies. The purpose of this study was to examine age-related expression patterns of these signaling molecules, in particular MT, SIRT1, SIRT3, and SIRT6 in BE of subjects of different ages with and without arterial hypertension (AH). We used real-time polymerase chain reaction (RT-PCR) and immunofluorescence analysis by confocal microscopy. We found that MT immunofluorescence intensity in BE decreases with aging, more evidently in AH patients. SIRT3 and SIRT6 genes expression and immunofluorescence intensity in BE was decreased in aging controls. In AH patients, SIRT1, SIRT3, and SIRT6 gene expression and immunofluorescence intensity in BE was decreased in relation to age and in comparison with age-matched controls. In conclusion, the evaluation of MT and sirtuins in BE could provide a non-invasive method for appraising the aging process, also when accompanied by AH.

scholarly journals Reconstruction of input functions from a dynamic PET image with sequential administration of 15O2 and H215O for noninvasive and ultra-rapid measurement of CBF, OEF, and CMRO2

2017 ◽  
Vol 38 (5) ◽  
pp. 780-792 ◽  
Author(s):  
Nobuyuki Kudomi ◽  
Yukito Maeda ◽  
Hiroyuki Yamamoto ◽  
Yuka Yamamoto ◽  
Tetsuhiro Hatakeyama ◽  
...  
Keyword(s):  
Rate Constants ◽  
Human Subjects ◽  
Invasive Procedure ◽  
Invasive Technique ◽  
Invasive Approach ◽  
Non Invasive ◽  
Sequential Administration ◽  
Invasive Method ◽  
The Difference ◽  
Arterial Input Functions

CBF, OEF, and CMRO2 images can be quantitatively assessed using PET. Their image calculation requires arterial input functions, which require invasive procedure. The aim of the present study was to develop a non-invasive approach with image-derived input functions (IDIFs) using an image from an ultra-rapid O2 and C15O2 protocol. Our technique consists of using a formula to express the input using tissue curve with rate constants. For multiple tissue curves, the rate constants were estimated so as to minimize the differences of the inputs using the multiple tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects ( n = 24). The estimated IDIFs were well-reproduced against the measured ones. The difference in the calculated CBF, OEF, and CMRO2 values by the two methods was small (<10%) against the invasive method, and the values showed tight correlations ( r = 0.97). The simulation showed errors associated with the assumed parameters were less than ∼10%. Our results demonstrate that IDIFs can be reconstructed from tissue curves, suggesting the possibility of using a non-invasive technique to assess CBF, OEF, and CMRO2.

Testicular responsiveness to hCG during infancy measured by salivary testosterone

1990 ◽  
Vol 123 (6) ◽  
pp. 633-636 ◽  
Author(s):  
Leo Dunkel ◽  
Ilpo Huhtaniemi
Keyword(s):  
Serum Testosterone ◽  
Maximal Level ◽  
Salivary Testosterone ◽  
Non Invasive ◽  
Basal Serum ◽  
Age Related ◽  
Invasive Method ◽  
Prepubertal Boys ◽  
The Mean

Abstract. To investigate the role of gonadotropins in postnatal testicular activation, testosterone responsiveness to human chorionic gonadotropin was studied in 11 male infants (aged 5-180 days). The boys were given a single im injection of 5000 IU/1.7m2 hCG, and serum and salivary testosterone responses were then measured for 7 days. The results were compared with the serum testosterone responses of 8 older prepubertal boys (aged 1.7-10.4 years) studied with the same protocol. The mean (±sem) basal serum testosterone levels were 2.67±1.27 nmol/l in the infants and 0.09±0.02 nmol/l in the prepubertal boys (p<0.05). Both groups gave a significant response to hCG stimulation (p<0.001, ANOVA, one-way). The stimulated concentrations of serum testosterone were higher in the infants than in the prepubertal boys (p<0.001). The mean basal level of salivary testosterone was 30.5 ±7.0 and the mean maximal level was 97± 10.3 pmol/l in the infants (p<0.001). No age-related changes were observed in either basal or hCG-stimulated levels. In infants the mean (±sem) maximal hCG-stimulated increase was 25 ± 10-fold in serum and 8±4-fold in saliva (p=0.13). A clear stimulatory effect of hCG on testicular testosterone production was found, suggesting that the postnatal increase in serum testosterone concentration in male infants is gonadotropin-mediated. Salivary testosterone concentrations can be increased by hCG, indicating that measurements of salivary testosterone may provide an optional, non-invasive method for assessing gonadal function in children.

scholarly journals Age-Related Changes in Methylome and Transcriptome of Hematopotietic Stem Cells Underlie Natural Genetic Variations

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2660-2660
Author(s):  
Ying Liang
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Stem Cell ◽  
Aging Process ◽  
Expression Patterns ◽  
Genetic Variations ◽  
Cell Aging ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Age Related Changes

The aging of hematopoietic stem cells (HSCs) contributes to the aging of blood system and perhaps the whole organism. The aging process is coordinately determined by both genetic and epigenetic factors, and demonstrates inter-individual variations. We used high-throughput sequencing methods to study the age-dependent changes of genome-wide DNA methylation and gene expression patterns in HSCs of C57BL/6 (B6) and DBA/2 mouse strains, which have shown natural variations in HSC aging process. We observed global age-associated decrease of DNA methylation in both strains, but D2 HSCs have a stronger loss of epigenetic control than B6 stem cells during aging. Majority age-related changes of DNA methylation occur from young to mid-aged stages. We identified stable strain-specific differentially methylated regions (DMRs) that overlap with cis-eQTLs. Moreover, transcription factor binding site motifs are more likely to be disrupted in the DMRs, suggesting the potential impact of genetic variations on epigenetic regulation of HSC aging. We further demonstrated that strain-specific DMRs have more profound effects on the aging of B6 HSCs than D2 stem cells. Transposons are differentially regulated by the DMRs in the two strains, in which D2 HSCs are prone to transposon insertion. This study comprehensively investigated the effects of natural genetic and epigenetic variations on HSC aging. Loss of DNA methylation is an epigenetic signature of stem cell aging, and DNA methylation variations correlates with genetic variations, both contributing to inter-individual differences in stem cell and perhaps organismal aging. Disclosures No relevant conflicts of interest to declare.

Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

2019 ◽  
Vol 25 (39) ◽  
pp. 4139-4149 ◽  
Author(s):  
Francesco Guarasci ◽  
Patrizia D'Aquila ◽  
Alberto Montesanto ◽  
Andrea Corsonello ◽  
Dina Bellizzi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Aging Process ◽  
Healthy Aging ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Biological Aging ◽  
Biomarkers Of Aging ◽  
Age Related

: Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging. : In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications. : Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

scholarly journals Multifaceted deregulation of gene expression and protein synthesis with age

2020 ◽  
Vol 117 (27) ◽  
pp. 15581-15590 ◽  
Author(s):  
Aleksandra S. Anisimova ◽  
Mark B. Meerson ◽  
Maxim V. Gerashchenko ◽  
Ivan V. Kulakovskiy ◽  
Sergey E. Dmitriev ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Cell Function ◽  
Altered Expression ◽  
Biomarkers Of Aging ◽  
Expression Of Genes ◽  
Age Related ◽  
Mouse Tissues ◽  
Terminal Oligopyrimidine ◽  
Age Related Changes

Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both the transcriptome and translatome of mouse tissues over the entire life span. We showed that the transcriptome changes govern those in the translatome and are associated with altered expression of genes involved in inflammation, extracellular matrix, and lipid metabolism. We also identified genes that may serve as candidate biomarkers of aging. At the translational level, we uncovered sustained down-regulation of a set of 5′-terminal oligopyrimidine (5′-TOP) transcripts encoding protein synthesis and ribosome biogenesis machinery and regulated by the mTOR pathway. For many of them, ribosome occupancy dropped twofold or even more. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and increased near stop codons, revealing complex age-related changes in the translation process. Taken together, our results reveal systematic and multidimensional deregulation of protein synthesis, showing how this major cellular process declines with age.

scholarly journals Multi-faceted deregulation of gene expression and protein synthesis with age

2020 ◽  
Author(s):  
Aleksandra S. Anisimova ◽  
Mark B. Meerson ◽  
Maxim V. Gerashchenko ◽  
Ivan V. Kulakovskiy ◽  
Sergey E. Dmitriev ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Cell Function ◽  
Altered Expression ◽  
Biomarkers Of Aging ◽  
Expression Of Genes ◽  
Age Related ◽  
Mouse Tissues ◽  
Terminal Oligopyrimidine ◽  
Age Related Changes

Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both the transcriptome and translatome of mouse tissues over the entire lifespan. Expression of the majority of differentially expressed genes followed a U-shaped curve with the turning point around 3-months-old. We showed that transcriptome changes govern changes in the translatome and are associated with altered expression of genes involved in inflammation, extracellular matrix and lipid metabolism. We also identified genes that may serve as candidate biomarkers of aging. At the translational level, we uncovered sustained down-regulation of a set of 5’ terminal oligopyrimidine (5’TOP) transcripts encoding protein synthesis and ribosome biogenesis machinery and regulated by the mTOR pathway. For many of them, ribosome occupancy dropped 3-fold or even more. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and increased near stop codons, revealing complex age-related changes in the translation process. Taken together, our results reveal systematic and multi-dimensional deregulation in protein synthesis, showing how this major cellular process declines with age.

scholarly journals Melatonin: the possibility to analyze the marker of age-related pathology in buccal epithelium and urine

2017 ◽  
Vol 95 (2) ◽  
pp. 136-139
Author(s):  
S. S. Konovalov ◽  
V. O. Polyakova ◽  
A. O. Drobintseva ◽  
I. M. Kvetnoy ◽  
T. V. Kvetnaya ◽  
...  
Keyword(s):  
Elderly People ◽  
Endocrine System ◽  
Functional Condition ◽  
Macular Dystrophy ◽  
Buccal Epithelium ◽  
Buccal Cells ◽  
Non Invasive ◽  
Age Related ◽  
Invasive Diagnostics

Extrapineal and pineal melatonin is the marker of the aging rate of organism making it possible to characterize functional condition of the neuro-immuno-endocrine system. In this article we have used the new method for non-invasive diagnostics of melatonin expression in buccal epithelium and determination of the main melatonin metabolite 6-hydroxymelatonin sulfate (6-HMS) in urine of elderly people. Normal, impaired and enhanced melatonin expression was documented in 20.5%, 43.2% and 36.30% of the patients respectively. Such comprehensive melatonin and 6-COMT studies can be recommended for elderly patients with oncological, neurodegenerative, cardiovascular diseases, and ageing macular dystrophy. Moreover, melatonin expression analysis in buccal cells can be used for integral investigation of biorhythms in elderly people.

scholarly journals Restriction of caloric intake is a key to prevention of vascular ageing

2015 ◽  
Vol 12 (2) ◽  
pp. 89-95
Author(s):  
Ya A Orlova
Keyword(s):  
Blood Pressure ◽  
Aging Process ◽  
Caloric Intake ◽  
Total Risk ◽  
Slowing Down ◽  
Physiological Processes ◽  
Biomarkers Of Aging ◽  
Daily Caloric Intake ◽  
Age Related ◽  
Vascular Ageing

Studies in recent decades suggest that slowing down the aging process is now real. We describe a number of physiological processes, which may affect the mortality and age-related deterioration of the functional state. One of the most studied impact is to limit caloric intake, which implies a decrease in daily caloric intake by 30-50% compared with an unlimited meal.Showing the effects of GST on the total risk of developing cardiovascular disease, different biomarkers of aging in people without obesity, blood pressure, and others.

scholarly journals New Computational Approaches to Aging Research

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 736-736
Author(s):  
Morgan E Levine
Keyword(s):  
Aging Process ◽  
Molecular Level ◽  
Biological Aging ◽  
Systems Dynamics ◽  
Learning Approaches ◽  
Biological Organization ◽  
Aging Research ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Novel Biomarkers

Abstract Aging is associated with numerous changes at all levels of biological organization. Harnessing this information to develop measures that accurately and reliably quantify the biological aging process will require systems biology approaches. This talk will illustrate how epigenetic data can be integrated with cellular, physiological, proteomic, and clinical data to model age-related changes that propagate up the levels—finally manifesting as age-related disease or death. I will also describe how network modeling and machine learning approaches (linear and non-linear) can be used to identify causal features in aging from which to generate novel biomarkers. Given the complexity of the biological aging process, modeling of systems dynamics over time will both lead to the development of better biomarkers of aging, and also inform our conceptualization of how alterations at the molecular level propagate up levels of organization to eventually influence morbidity and mortality risk.

Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

2001 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
Gertraud Teuchert-Noodt ◽  
Ralf R. Dawirs
Keyword(s):  
Prefrontal Cortex ◽  
Mental Disorders ◽  
Dentate Gyrus ◽  
Cognitive Functions ◽  
Experimental Approach ◽  
Regulatory Mechanisms ◽  
Hippocampal Dentate Gyrus ◽  
Non Invasive ◽  
Invasive Method ◽  
Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

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