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Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers

Plasma transfusions are standard treatments to replace missing proteins in people with rare genetic diseases. Prior studies have demonstrated that heterochronic parabiosis has beneficial effects on several tissues of old animals receiving young blood. Human clinical trials are currently underway to...

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Autores principales: Clement, James, Yan, Qi, Agrawal, Megha, Coronado, Ramon E., Sturges, John A., Horvath, Markus, Lu, Ake T., Brooke, Robert T., Horvath, Steve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577957/
https://www.ncbi.nlm.nih.gov/pubmed/36052758
http://dx.doi.org/10.1111/acel.13696
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author Clement, James
Yan, Qi
Agrawal, Megha
Coronado, Ramon E.
Sturges, John A.
Horvath, Markus
Lu, Ake T.
Brooke, Robert T.
Horvath, Steve
author_facet Clement, James
Yan, Qi
Agrawal, Megha
Coronado, Ramon E.
Sturges, John A.
Horvath, Markus
Lu, Ake T.
Brooke, Robert T.
Horvath, Steve
author_sort Clement, James
collection PubMed
description Plasma transfusions are standard treatments to replace missing proteins in people with rare genetic diseases. Prior studies have demonstrated that heterochronic parabiosis has beneficial effects on several tissues of old animals receiving young blood. Human clinical trials are currently underway to investigate whether the infusion of plasma or plasma‐derived factors from young donors can be used to mitigate human age‐related conditions. Here, we use data from a safety study (n = 18, mean age 74) to investigate whether human umbilical cord plasma concentrate (hereinafter Plasma Concentrate) injected weekly (1 ml intramuscular) into elderly human subjects over a 10‐week period affects different biomarkers, including epigenetic age measures, standard clinical biomarkers of organ dysfunction, mitochondrial DNA copy number (mtDNA‐CN), and leukocyte telomere length. This study shows that treatment with plasma concentrate is safe. More than 20 clinical biomarkers were significantly and beneficially altered following the treatments. For example, creatinine was significantly decreased (p = 0.0039), while estimated glomerular filtration rate (eGFR) was increased (p = 0.0044), indicating the treatment may improve biomarkers of kidney function. Three of four immunoglobulin biomarkers decreased, while telomere length and mtDNA‐CN were not significantly affected by the treatment. The treatment reduced DNA methylation‐based GrimAge by an average of 0.82 years (p = 0.0093), suggests a reduction in morbidity and mortality risk. By contrast, no significant results could be observed for epigenetic clocks that estimate chronological age. Our results support the view that plasma concentrate contains youth‐promoting factors.
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spelling pubmed-95779572022-10-19 Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers Clement, James Yan, Qi Agrawal, Megha Coronado, Ramon E. Sturges, John A. Horvath, Markus Lu, Ake T. Brooke, Robert T. Horvath, Steve Aging Cell Research Articles Plasma transfusions are standard treatments to replace missing proteins in people with rare genetic diseases. Prior studies have demonstrated that heterochronic parabiosis has beneficial effects on several tissues of old animals receiving young blood. Human clinical trials are currently underway to investigate whether the infusion of plasma or plasma‐derived factors from young donors can be used to mitigate human age‐related conditions. Here, we use data from a safety study (n = 18, mean age 74) to investigate whether human umbilical cord plasma concentrate (hereinafter Plasma Concentrate) injected weekly (1 ml intramuscular) into elderly human subjects over a 10‐week period affects different biomarkers, including epigenetic age measures, standard clinical biomarkers of organ dysfunction, mitochondrial DNA copy number (mtDNA‐CN), and leukocyte telomere length. This study shows that treatment with plasma concentrate is safe. More than 20 clinical biomarkers were significantly and beneficially altered following the treatments. For example, creatinine was significantly decreased (p = 0.0039), while estimated glomerular filtration rate (eGFR) was increased (p = 0.0044), indicating the treatment may improve biomarkers of kidney function. Three of four immunoglobulin biomarkers decreased, while telomere length and mtDNA‐CN were not significantly affected by the treatment. The treatment reduced DNA methylation‐based GrimAge by an average of 0.82 years (p = 0.0093), suggests a reduction in morbidity and mortality risk. By contrast, no significant results could be observed for epigenetic clocks that estimate chronological age. Our results support the view that plasma concentrate contains youth‐promoting factors. John Wiley and Sons Inc. 2022-09-02 2022-10 /pmc/articles/PMC9577957/ /pubmed/36052758 http://dx.doi.org/10.1111/acel.13696 Text en © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Clement, James
Yan, Qi
Agrawal, Megha
Coronado, Ramon E.
Sturges, John A.
Horvath, Markus
Lu, Ake T.
Brooke, Robert T.
Horvath, Steve
Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
title Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
title_full Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
title_fullStr Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
title_full_unstemmed Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
title_short Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
title_sort umbilical cord plasma concentrate has beneficial effects on dna methylation grimage and human clinical biomarkers
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577957/
https://www.ncbi.nlm.nih.gov/pubmed/36052758
http://dx.doi.org/10.1111/acel.13696
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