scholarly journals Whole Blood Metabolomics in Aging Research

2020 ◽  
Vol 22 (1) ◽  
pp. 175
Author(s):  
Hiroshi Kondoh ◽  
Masahiro Kameda ◽  
Mitsuhiro Yanagida
Keyword(s):  
Whole Blood ◽  
Experimental Models ◽  
Individual Variability ◽  
Human Longevity ◽  
Biological Aging ◽  
Epigenetic Factors ◽  
Aging Research ◽  
Targeted Analysis ◽  
Complex Biological Process ◽  
Global Aging

Diversity is observed in the wave of global aging because it is a complex biological process exhibiting individual variability. To assess aging physiologically, markers for biological aging are required in addition to the calendar age. From a metabolic perspective, the aging hypothesis includes the mitochondrial hypothesis and the calorie restriction (CR) hypothesis. In experimental models, several compounds or metabolites exert similar lifespan-extending effects, like CR. However, little is known about whether these metabolic modulations are applicable to human longevity, as human aging is greatly affected by a variety of factors, including lifestyle, genetic or epigenetic factors, exposure to stress, diet, and social environment. A comprehensive analysis of the human blood metabolome captures complex changes with individual differences. Moreover, a non-targeted analysis of the whole blood metabolome discloses unexpected aspects of human biology. By using such approaches, markers for aging or aging-relevant conditions were identified. This information should prove valuable for future diagnosis or clinical interventions in diseases relevant to aging.

scholarly journals Sex differences in biological aging with a focus on human studies

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sara Hägg ◽  
Juulia Jylhävä
Keyword(s):  
Sex Differences ◽  
Sex Chromosome ◽  
Current Knowledge ◽  
Individual Variability ◽  
Human Studies ◽  
Biological Aging ◽  
Theories Of Aging ◽  
Age Related ◽  
Complex Biological Process ◽  
The Life Course

Aging is a complex biological process characterized by hallmark features accumulating over the life course, shaping the individual's aging trajectory and subsequent disease risks. There is substantial individual variability in the aging process between men and women. In general, women live longer than men, consistent with lower biological ages as assessed by molecular biomarkers, but there is a paradox. Women are frailer and have worse health at the end of life, while men still perform better in physical function examinations. Moreover, many age-related diseases show sex-specific patterns. In this review, we aim to summarize the current knowledge on sexual dimorphism in human studies, with support from animal research, on biological aging and illnesses. We also attempt to place it in the context of the theories of aging, as well as discuss the explanations for the sex differences, for example, the sex-chromosome linked mechanisms and hormonally driven differences.

scholarly journals Influence of study model, baseline catalytic concentrations and analytical system on the stability of serum alanine aminotransferase

2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Josep Miquel Bauça ◽  
Andrea Caballero ◽  
Carolina Gómez ◽  
Débora Martínez-Espartosa ◽  
Isabel García del Pino ◽  
...  
Keyword(s):  
Alanine Aminotransferase ◽  
Experimental Models ◽  
Individual Variability ◽  
Serum Samples ◽  
Multicentric Study ◽  
Different Temperatures ◽  
The Stability ◽  
Analytical System ◽  
Definition Of ◽  
Analytical Platforms

AbstractObjectivesThe stability of the analytes most commonly used in routine clinical practice has been the subject of intensive research, with varying and even conflicting results. Such is the case of alanine aminotransferase (ALT). The purpose of this study was to determine the stability of serum ALT according to different variables.MethodsA multicentric study was conducted in eight laboratories using serum samples with known initial catalytic concentrations of ALT within four different ranges, namely: <50 U/L (<0.83 μkat/L), 50–200 U/L (0.83–3.33 μkat/L), 200–400 U/L (3.33–6.67 μkat/L) and >400 U/L (>6.67 μkat/L). Samples were stored for seven days at two different temperatures using four experimental models and four laboratory analytical platforms. The respective stability equations were calculated by linear regression. A multivariate model was used to assess the influence of different variables.ResultsCatalytic concentrations of ALT decreased gradually over time. Temperature (−4%/day at room temperature vs. −1%/day under refrigeration) and the analytical platform had a significant impact, with Architect (Abbott) showing the greatest instability. Initial catalytic concentrations of ALT only had a slight impact on stability, whereas the experimental model had no impact at all.ConclusionsThe constant decrease in serum ALT is reduced when refrigerated. Scarcely studied variables were found to have a significant impact on ALT stability. This observation, added to a considerable inter-individual variability, makes larger studies necessary for the definition of stability equations.

Clinical Translation of Anti-aging Associated Genetics: Current Progress and Challenges

2021 ◽  
Vol 14 ◽  
Author(s):  
Yi Wang
Keyword(s):  
Genetic Manipulation ◽  
Large Body ◽  
Cost Effective ◽  
Clinical Applications ◽  
Biological Aging ◽  
Aging Research ◽  
Gene Therapies ◽  
Molecular Approaches ◽  
Gerontological Research ◽  
Tremendous Challenge

Background: Currently, the focus of anti-aging research has been changed from geriatrics to biogerontology. This has taken anti-aging strategies from cost-effective but palliative therapeutics to active, molecular approaches. Outline: Over the years, a large body of basic gerontological research has indicated that the process of biological aging is closely associated with genetic factors. This leads to the development of various gene therapies such as RNA interference technology and results in a subsequent need of translating laboratory achievements into clinical applications. The translation has been a tremendous challenge at this stage with respect to practicality, safety and effectiveness of the genetic manipulation techniques. Objective: This review summarizes the current development of anti-aging strategies and the progress in the translation of laboratory achievements into clinical applications, highlights challenges encountered, and provides a prospective outlook for future anti-aging research.

scholarly journals Integrated Transcriptome, Proteome, Acetylome, and Metabolome Profiling of Mouse Liver During Normal Aging

2020 ◽  
Author(s):  
Jiang-Feng Liu ◽  
Song-Feng Wu ◽  
Cong Liu ◽  
Hou-Zao Chen ◽  
Juntao Yang
Keyword(s):  
Immune Function ◽  
Mouse Liver ◽  
Functional Decline ◽  
Normal Aging ◽  
Arachidonic Acid Metabolism ◽  
Functional Enrichment ◽  
Metabolome Analysis ◽  
Aging Research ◽  
Complex Biological Process ◽  
Old Mice

Abstract BackgroundAging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. We aimed to obtain an integrated aging-associated profile of the mouse liver using a multi-omics approach.ResultsWe performed a combined transcriptome, proteome, acetylome, and metabolome analysis of liver tissues from young and old mice under physiological conditions. Old mice were frequently obese with a fatty liver, and the observed profile changes in different omics were generally moderate. Specifically, transcriptome, proteome, and acetylome analyses revealed different patterns in old and young mice, but metabolome analysis did not. Functional enrichment analysis showed that metabolic pathways were broadly altered during normal aging. Notably, the genes, proteins, and metabolites involved in pyrimidine and glutathione metabolisms were significantly affected in all these four omics. Moreover, we observed increased arachidonic acid metabolism and decreased complement and coagulation cascades in old mice, suggesting an alteration in the immune function during normal aging.ConclusionsWe conducted a multi-omics investigation of normal liver aging in mice and generated comprehensive datasets for aging research. Further analysis revealed that impairment of pyrimidine and glutathione metabolisms and immune function may be critical for hepatic aging and may provide targets for aging interventions.

scholarly journals Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Amedeo De Nicolò ◽  
Michele Pinon ◽  
Alice Palermiti ◽  
Antonello Nonnato ◽  
Alessandra Manca ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Pediatric Patients ◽  
Mononuclear Cells ◽  
Individual Variability ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Intracellular Concentrations ◽  
The One

Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC–MS/MS assay over a period of 2–3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of −0.1% (IQR −22.4%–+46.9%) between timings: this intra-individual variability was similar to the one in WB, −2.9% (IQR −29.4–+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations.

scholarly journals Predictors of Biological Age: The Implications for Wellness and Aging Research

2021 ◽  
Vol 7 ◽  
pp. 233372142110464
Author(s):  
Trevor Lohman ◽  
Gurinder Bains ◽  
Lee Berk ◽  
Everett Lohman
Keyword(s):  
Dna Methylation ◽  
Lifestyle Modification ◽  
Biological Age ◽  
Current Evidence ◽  
Biological Aging ◽  
Clinical Value ◽  
Aging Research ◽  
Mortality And Morbidity ◽  
Morbidity Risk ◽  
Pharmaceutical Interventions

As healthspan and lifespan research breakthroughs have become more commonplace, the need for valid, practical markers of biological age is becoming increasingly paramount. The accessibility and affordability of biological age predictors that can reveal information about mortality and morbidity risk, as well as remaining years of life, has profound clinical and research implications. In this review, we examine 5 groups of aging biomarkers capable of providing accurate biological age estimations. The unique capabilities of these biomarkers have far reaching implications for the testing of both pharmaceutical and non-pharmaceutical interventions designed to slow or reverse biological aging. Additionally, the enhanced validity and availability of these tools may have increasingly relevant clinical value. The authors of this review explore those implications, with an emphasis on lifestyle modification research, and provide an overview of the current evidence regarding 5 biological age predictor categories: Telomere length, composite biomarkers, DNA methylation “epigenetic clocks,” transcriptional predictors of biological age, and functional age predictors.

scholarly journals EPIGENETICS OF STRESS AND ADAPTATION ACROSS HEALTHSPAN AND LIFESPAN

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S735-S735
Author(s):  
Luigi Ferrucci ◽  
Shabnam Salimi ◽  
Luigi Ferrucci
Keyword(s):  
Stress Response ◽  
Chronic Diseases ◽  
Accelerated Aging ◽  
Premature Mortality ◽  
Individual Variability ◽  
Biological Aging ◽  
Increased Risk ◽  
Approaches To Study ◽  
Rate Of Decline ◽  
Aging Phenomena

Abstract Any stimulus that endangers body integrity (stressor) results in an adaptive response to resolve stressful state and determine adaptive or and maladaptive responses. Both chronic extrinsic and intrinsic stressors can produce long-lasting, epigenetic changes in various organs that can eventually result in accelerated changes in bio-physio-pathology. There is initial evidence that stress response involves mechanisms of the epigenetic basis of adaptation and stress response to biological aging and chronic diseases. With aging, homeostasis stability declines causing augmented vulnerability to the external and internal stress. Individuals in whom vulnerability trespass a certain threshold experience accelerated aging and deterioration of health and/ or “secondary aging” phenomena such as premature mortality. Because of substantial heterogeneity of the rate of decline in homeostatic stability, there is inter-individual variability in the age of appearance of chronic diseases and the increased risk of disability and mortality. Thus, tools for the quantification of a stress response would be clinically valuable. Therefore, this symposium suggests approaches to study the epigenetic basis of molecular adaptations across various age, organs’ health-span, and life-span.

Cultural Variance and Invariance of Age Differences in Social Cognition

2019 ◽  
Author(s):  
Li Chu ◽  
Yang Fang ◽  
Vivian Hiu-Ling Tsang ◽  
Helene H. Fung
Keyword(s):  
Social Cognition ◽  
Cognitive Processing ◽  
Social Cognitive ◽  
Self Regulation ◽  
Cultural Influences ◽  
Biological Aging ◽  
Aging Research ◽  
Age Related ◽  
Norms And Values ◽  
The One

Cognitive processing of social and nonsocial information changes with age. These processes range from the ones that serve “mere” cognitive functions, such as recall strategies and reasoning, to those that serve functions that pertain to self-regulation and relating to others. However, aging and the development of social cognition unfold in different cultural contexts, which may assume distinct social norms and values. Thus, the resulting age-related differences in cognitive and social cognitive processes may differ across cultures. On the one hand, biological aging could render age-related differences in social cognition universal; on the other hand, culture may play a role in shaping some age-related differences. Indeed, many aspects of cognition and social cognition showed different age and culture interactions, and this makes the study of these phenomena more complex. Future aging research on social cognition should take cultural influences into consideration.

Variables Associated with the Assessment of Systemic Tumor Necrosis Factor Alpha Levels during Hemodialysis

1992 ◽  
Vol 15 (11) ◽  
pp. 653-657 ◽  
Author(s):  
A. Jörres ◽  
P. Froese ◽  
C. Fischer ◽  
H. Safak ◽  
G.M. Gahl ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Whole Blood ◽  
Tumor Necrosis ◽  
Individual Variability ◽  
Necrosis Factor Alpha ◽  
Cross Sectional ◽  
Factor Alpha ◽  
Necrosis Factor

Conflicting results have been published concerning the systemic induction of the cytokine tumor necrosis factor alpha (TNFα) during hemodialysis (HD). We therefore evaluated in vitro TNFα production in whole blood as well as in vivo variability of TNFα levels in patients on long-term HD. Whole blood was incubated at room temperature (RT) with or without exogenously added endotoxin (ET), and plasma-TNFα was measured after 5, 30, 120, 240, and 960 min by specific enzyme immunoassay. Additionally, plasma-TNFα before and after 120 and 240 min HD was studied longitudinally once a week over a period of 4 weeks in 36 patients on Cuprophan® (CU, n=23) or polysulfone-F60 (PSu, n=13) HD. Mean plasma TNFα levels in vitro rose from (mean) 8 pg/ml after 5 min to 12 pg/ml (120′) and 32 pg/ml (960′) even without ET addition, and to 18 pg/ml (after 120′) and 88 pg/ml (after 960′) when 0.1 μg/ml ET were added. Pre-dialytic as well as intradialytic TNFα levels in patients showed high intra-individual variability. A substantial (> 100%) increase in plasma TNFα was observed during only 14 out of 84 treatments with CU and 20 out of 47 with PSu, however, the increase in TNFα was not statistically significant in either group. We conclude that the sampling procedure, if not carefully standardized, is a potential source of artifacts with regard to “systemic” TNFα levels. The high intra and inter-individual variability of plasma TNFα suggests that results of cross-sectional studies are questionable.

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