The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase

Aging is a natural process with concomitant changes in the gut microbiota and associate metabolomes. Beta-nicotinamide mononucleotide, an important NAD+ intermediate, has drawn increasing attention to retard the aging process. We probed the changes in the fecal microbiota and metabolomes of pre-aging male mice (C57BL/6, age: 16 months) following the oral short-term administration of nicotinamide mononucleotide (NMN). Considering the telomere length as a molecular gauge for aging, we measured this in the peripheral blood mononuclear cells (PBMC) of pre-aging mice and human volunteers (age: 45–60 years old). Notably, the NMN administration did not influence the body weight and feed intake significantly during the 40 days in pre-aging mice. Metabolomics suggested 266 upregulated and 58 downregulated serum metabolites. We identified 34 potential biomarkers linked with the nicotinamide, purine, and proline metabolism pathways. Nicotinamide mononucleotide significantly reduced the fecal bacterial diversity (p < 0.05) with the increased abundance of Helicobacter, Mucispirillum, and Faecalibacterium, and lowered Akkermansia abundance associated with nicotinamide metabolism. We propose that this reshaped microbiota considerably lowered the predicated functions of aging with improved immune and cofactors/vitamin metabolism. Most notably, the telomere length of PBMC was significantly elongated in the NMN-administered mice and humans. Taken together, these findings suggest that oral NMN supplementation in the pre-aging stage might be an effective strategy to retard aging. We recommend further studies to unravel the underlying molecular mechanisms and comprehensive clinical trials to validate the effects of NMN on aging.

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Telomere Shortening in Formerly Abused and Never Abused Women

Biological Research For Nursing ◽

10.1177/1099800411398479 ◽

2011 ◽

Vol 14 (2) ◽

pp. 115-123 ◽

Cited By ~ 64

Author(s):

Janice Humphreys ◽

Elissa S. Epel ◽

Bruce A. Cooper ◽

Jue Lin ◽

Elizabeth H. Blackburn ◽

...

Keyword(s):

Telomere Length ◽

Chronic Stress ◽

Partner Violence ◽

Molecular Mechanisms ◽

Mononuclear Cells ◽

Quantitative Polymerase Chain Reaction ◽

Cellular Aging ◽

Abused Women ◽

Peripheral Blood Mononuclear ◽

Convenience Sample

Recent studies suggest that chronic psychological stress may accelerate aging at the cellular level. Telomeres are protective components that stabilize the ends of chromosomes and modulate cellular aging. Women exposed to intimate partner violence (IPV) experience chronic stress and report worse health. The purpose of this exploratory study was to examine telomeric DNA length in women who have experienced chronic stress related to IPV. We hypothesized that IPV exposure would be associated with shorter telomere length. The investigation used a cross-sectional design to study telomere length in women with a history of IPV exposure and control women who reported no prior exposure to IPV. Advertisements and public notices were used to recruit a convenience sample of healthy women. Mean leukocyte telomere length was measured in DNA samples from peripheral blood mononuclear cells (PBMCs) by a quantitative polymerase chain reaction assay (qPCR). Telomere length was significantly shorter in the 61 formerly abused women compared to the 41 controls ( t = 2.4, p = .02). Length of time in the abusive relationship and having children were associated with telomere length after controlling for age and body mass index (BMI) ( F(2, 99) = 10.23, p < .001). Numerous studies suggest that women who experience IPV have poorer overall health. It is often presumed that the stress of IPV may be causing greater morbidity. Findings from this descriptive study suggest a link between IPV exposure, duration of IPV-related stress, and telomere length molecular mechanisms that regulate cellular aging.

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A pilot study evaluating surrogates of response to short-term vorinostat in women with newly diagnosed breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14508 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14508-e14508

Author(s):

V. Stearns ◽

L. K. Jacobs ◽

T. N. Tsangaris ◽

S. Briest ◽

J. R. Lange ◽

...

Keyword(s):

Breast Cancer ◽

Histone Acetylation ◽

Mononuclear Cells ◽

Clinical Stage ◽

Study Drug ◽

Gene Methylation ◽

Short Term ◽

Peripheral Blood Mononuclear ◽

Hormone Receptor Positive ◽

Term Administration

e14508 Background: Epigenetic modifications contribute to breast cancer initiation and progression and may be reversible, thus representing an attractive area for new drug investigation. In preclinical breast cancer models, the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) induces cell cycle arrest, apoptosis and differentiation. Methods: We evaluated the safety and tolerability of short term vorinostat in women with a primary clinical stage I-III histologically confirmed carcinoma of the breast on a core needle biopsy. Participants received vorinostat 300 mg PO bid for a total of 6 doses, the last dose 2 hours prior to surgery or biopsy. Peripheral blood mononuclear cells were collected at baseline and following the last vorinostat dose to determine histone acetylation. Baseline and post-treatment tumor specimens were collected for analysis of histone acetylation, candidate gene methylation and expression. Tissues were also collected from untreated controls. Paired t-tests and Fisher's exact tests were used to evaluate changes from baseline for continuous and categorical data, respectively. Results: From March 2006 to October 2008, 25 women signed an informed consent and initiated study drug. Median age was 55 and 80% had hormone receptor positive tumors. Twenty-two women took all 6 prescribed doses. One participant took 4 and one 5 doses due to insurance clearance delay; one received a single dose due to fatigue and abdominal pain. Study-related surgical delays did not occur. Grade 1 toxicities included diarrhea (28%), low white blood cell count (24%), and fatigue, taste alterations and nausea (16% each). Tissue and blood samples were successfully collected. Tissue was also collected from 25 untreated controls. No significant change was observed in the proliferation marker Ki67 following 3 days of agent administration. Modulation of apoptosis, histone acetylation and gene methylation will be presented. Conclusions: Short-term administration of vorinostat is feasible, safe, and allows for studies of biomarker modulation. The results will be used to design future studies in which vorinostat will be administered in combination with other targeted therapies or with other epigenetic modifiers. [Table: see text]

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PSVI-24 Immunological Effects of a Purified 1,3/1,6 β-glucan Supplementation in Retorted Canine Diets

Journal of Animal Science ◽

10.1093/jas/skaa278.558 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 313-313

Author(s):

Zac Traughber ◽

Fei He ◽

Maria R C de Godoy

Keyword(s):

Mononuclear Cells ◽

Control Diet ◽

Fecal Microbiota ◽

Significant Treatment ◽

Peripheral Blood Mononuclear ◽

Immune Parameters ◽

Randomized Design ◽

Diet Formulation ◽

Respective Treatment ◽

Branched Chain

Abstract Yeast cell wall products are common functional ingredients capable of “priming” the immune system, specifically in reference to vaccine efficacy. Twenty-four adult, female Beagles were used in a completely randomized design. Three retorted diets were used: control diet (CON), CON plus β-glucan top-dressed daily upon time of feeding (C+B), and CON plus retorted β-glucan included in diet formulation (BG). Following a 7 d adaptation to CON, dogs were fed their respective treatment diets for 42 d and were challenged with an oral Bordetella bronchiseptica vaccine on d 14 with blood collections on d 0, 21, 28, and 42. The objectives of the present study were 1) to evaluate the effects of dietary inclusion of a yeast β-1,3/1,6 glucan (150 ppm) on apparent total tract digestibility (ATTD) of macronutrients, fecal microbiota, and peripheral blood mononuclear cells (PBMC; T-cells, B-cells, and monocytes) of adult dogs and, 2) to test the effects of retorting on the efficacy of these β-glucans. All diets were well-accepted by all dogs. ATTD of both dry matter and crude protein were greater (P < 0.05) for BG than CON and with greater (P < 0.05) energy digestibility for BG than both B+G and CON. Additionally, fecal short-chain and branched-chain fatty acids, ammonia, indole and phenol concentrations did not differ among treatments. No significant treatment by time interactions among treatment groups were observed for any analyzed PBMC. These data suggest that a 150 ppm inclusion of this yeast-derived β-glucan had no detrimental effects on ATTD, fecal characteristics and metabolites, nor any analyzed PBMC; however, due to the absence of differences in immune parameters among treatments, the effect of retorting on the efficacy of this product cannot confidently be assessed with these findings. Higher doses of yeast-derived β-glucan might be needed to elicit an immunological modulation in healthy adult dogs.

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Impact of Delaying Antiretroviral Treatment during Primary HIV Infection on Telomere Length

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab186 ◽

2021 ◽

Author(s):

Marieke Raffenberg ◽

Tanja Engel ◽

Isabella C Schoepf ◽

Neeltje A Kootstra ◽

Peter Reiss ◽

...

Keyword(s):

Hiv Infection ◽

Telomere Length ◽

Antiretroviral Treatment ◽

Mononuclear Cells ◽

Multivariable Analysis ◽

Limited Effect ◽

Peripheral Blood Mononuclear ◽

Primary Hiv Infection ◽

Hiv Seroconversion ◽

Chronic Hiv Infection

Abstract Background Telomere length (TL) shortens during aging, HIV-seroconversion and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI). Methods We measured TL in peripheral blood mononuclear cells by quantitative PCR in participants of the Zurich PHI Study with samples available for >6 years. We obtained uni-/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL. Results In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the 1 st (shortest), 2 nd, and 3 rd (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (p for trend=0.034), and longer TL over 6 years, but only with continuous ART (p<0.001), not if ART was interrupted >12 months (p=0.408). In multivariable analysis, participants in the 2 nd and 3 rd ART delay tertile had 17.6% (5.4-29.7%; p=0.004) and 21.5% (9.4-33.5%; p<0.001) shorter TL, after adjustment for age, with limited effect modification by clinical variables. Discussion In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

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Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

10.1101/2021.12.17.472326 ◽

2021 ◽

Author(s):

Zhibin Li ◽

chengcheng Sun ◽

Fei Wang ◽

Xiran Wang ◽

Jiacheng Zhu ◽

...

Keyword(s):

Single Cell ◽

Immune Cells ◽

Evolutionary Biology ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Mononuclear Cells ◽

Immune Cell ◽

Cell Types ◽

Genetic Regulatory Networks ◽

Peripheral Blood Mononuclear

Background: Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods: In this study, we compared the single-cell transcriptomes of 77 957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results: The results revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular cross-talks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. Conclusions: This study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders

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Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

10.1101/2021.07.16.21260643 ◽

2021 ◽

Author(s):

Ning-Jiun Jan ◽

Noah Oakland ◽

Pankaj Kumar ◽

Girija Ramakrishnan ◽

Brian W. Behm ◽

...

Keyword(s):

Mononuclear Cells ◽

Fecal Microbiota Transplantation ◽

Alpha Diversity ◽

The United States ◽

Fecal Microbiota ◽

Peripheral Blood Mononuclear ◽

Clostridioides Difficile ◽

Rdna Sequencing ◽

Clostridioides Difficile Infection ◽

The Impact

Background: Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon. Methods: Subjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT. Results: All 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT. Conclusion: The increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

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Identification of Molecular Mechanisms in Parkinson’s Disease Pathogenesis: Significance of Survival and Inflammation Pathways

10.21203/rs.3.rs-41609/v1 ◽

2020 ◽

Author(s):

Zerrin Karaaslan ◽

Ozlem Timirci Kahraman ◽

Elif Sanli ◽

Hayriye Arzu Ergen ◽

Basar Bilgic ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Annotation ◽

Molecular Mechanisms ◽

Mononuclear Cells ◽

Neuronal Degeneration ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Rt Pcr ◽

Peripheral Blood Mononuclear

Abstract Background: Our aim was to identify the differentially expressed genes (DEGs) between Parkinson’s disease (PD) patients and controls by microarray technology and analysis of related molecular pathways by functional annotation. Methods: Thirty PD patients and 30 controls were enrolled. Agilent Human 8X60 K Oligo Microarray was used for gene level expression identification. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein-protein interaction analyses were performed with STRING. Expression levels of randomly selected 5 genes among DEGs were quantified by real time quantitative polymerase chain reaction (RT-PCR) for validation. Flow cytometry was done to determine frequency of regulatory T cells (Tregs) in peripheral blood mononuclear cells. Results: A total of 361 DEGs (143 upregulated and 218 downregulated) were identified after GeneSpring analysis. DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions. Pathway analyses demonstrated that upregulated genes mainly enriched in p53 (CASP3, TSC2, ATR, MDM4, CCNG1) and PI3K/Akt (IL2RA, IL4R, TSC2, VEGFA, PKN2, PIK3CA, ITGA4, BCL2L11) signaling pathways. TP53 and PIK3CA were identified as most significant hub proteins. Expression profiles obtained by RT-PCR were consistent with microarray findings. PD patients showed increased proportions of CD49d+ Tregs, which correlated with disability scores. Discussion: Survival pathway genes were upregulated putatively to compensate neuronal degeneration. Bioinformatics analysis showed an association between survival and inflammation genes. Increased CD49d+ Treg ratios might signify the attempt of the immune system to suppress ongoing inflammation. Conclusion: Altered functions of Tregs might have an important role in PD pathogenesis and CD49d expression could be a prognostic biomarker of PD.

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Age-related telomere length dynamics in peripheral blood mononuclear cells of healthy cynomolgus monkeys measured by Flow FISH

Immunology ◽

10.1046/j.1365-2567.2002.01386.x ◽

2002 ◽

Vol 105 (4) ◽

pp. 458-465 ◽

Cited By ~ 18

Author(s):

Won-Woo Lee ◽

Ki-Hoan Nam ◽

Keiji Terao ◽

Yasuhiro Yoshikawa

Keyword(s):

Telomere Length ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Cynomolgus Monkeys ◽

Age Related ◽

Blood Mononuclear Cells

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Glucocorticoids and Catecholamines Affect in Vitro Functionality of Porcine Blood Immune Cells

Animals ◽

10.3390/ani9080545 ◽

2019 ◽

Vol 9 (8) ◽

pp. 545 ◽

Cited By ~ 3

Author(s):

Lena Reiske ◽

Sonja Schmucker ◽

Julia Steuber ◽

Volker Stefanski

Keyword(s):

Immune Cells ◽

Lymphocyte Proliferation ◽

Molecular Mechanisms ◽

Mononuclear Cells ◽

Intracellular Cytokine Staining ◽

Stress Hormones ◽

High Stress ◽

Peripheral Blood Mononuclear ◽

Indwelling Catheters

Stress hormones exert important modulating influences on the functionality of immune cells. Despite its major role as a livestock animal and its increasing use as an animal model, knowledge about this relationship in the domestic pig is rare. This study therefore aimed to characterize the effect of glucocorticoids and catecholamines on the proliferation and cytokine production of porcine peripheral blood mononuclear cells (PBMC). Blood was obtained from donor pigs equipped with indwelling catheters to exclude stress hormone exposition before in vitro testing. PBMC were stimulated in the presence of cortisol, adrenaline or noradrenaline at concentrations resembling low to high stress conditions. Proliferation was determined via 3H-thymidine incorporation, and TNFα producers were quantified by intracellular cytokine staining. Cortisol led to a decrease in mitogen-induced lymphocyte proliferation and the number of TNFα producing cells. In contrast, catecholamines increased proliferation while exerting repressive or no effects on the number of cytokine producers. Remarkably, in concentrations presumably found in lymphatic tissue in stress situations, noradrenaline suppressed lymphocyte proliferation completely. The shown repressive effects might especially have implications on health and welfare in pigs. The obtained results provide a preliminary database for extended studies on the molecular mechanisms of glucocorticoid and catecholamine actions on porcine immune cells.

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