Literature DB >> 36052758

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

James Clement1,2, Qi Yan3, Megha Agrawal1, Ramon E Coronado4,5,6,7, John A Sturges8, Markus Horvath3, Ake T Lu9,10, Robert T Brooke3, Steve Horvath9,11.   

Abstract

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.
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Entities:  

Keywords:  clinical trial; epigenetic clocks; exosome treatment; umbilical cord plasma; young plasma

Mesh:

Substances:

Year:  2022        PMID: 36052758      PMCID: PMC9577957          DOI: 10.1111/acel.13696

Source DB:  PubMed          Journal:  Aging Cell        ISSN: 1474-9718            Impact factor:   11.005


  46 in total

1.  The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years.

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Journal:  Eur Heart J       Date:  2007-01-12       Impact factor: 29.983

Review 2.  Attenuation of frailty in older adults with mesenchymal stem cells.

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Journal:  Mech Ageing Dev       Date:  2019-06-07       Impact factor: 5.432

Review 3.  Cystatin C as a biomarker for estimating glomerular filtration rate.

Authors:  Thomas W Ferguson; Paul Komenda; Navdeep Tangri
Journal:  Curr Opin Nephrol Hypertens       Date:  2015-05       Impact factor: 2.894

Review 4.  Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease.

Authors:  Sudhir H Ranganath; Oren Levy; Maneesha S Inamdar; Jeffrey M Karp
Journal:  Cell Stem Cell       Date:  2012-03-02       Impact factor: 24.633

5.  GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality.

Authors:  Cathal McCrory; Giovanni Fiorito; Belinda Hernandez; Silvia Polidoro; Aisling M O'Halloran; Ann Hever; Cliona Ni Cheallaigh; Ake T Lu; Steve Horvath; Paolo Vineis; Rose Anne Kenny
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2021-04-30       Impact factor: 6.053

6.  HIV-1 Infection Accelerates Age According to the Epigenetic Clock.

Authors:  Steve Horvath; Andrew J Levine
Journal:  J Infect Dis       Date:  2015-05-12       Impact factor: 5.226

7.  DNA methylation-based estimator of telomere length.

Authors:  Ake T Lu; Anne Seeboth; Pei-Chien Tsai; Dianjianyi Sun; Austin Quach; Alex P Reiner; Charles Kooperberg; Luigi Ferrucci; Lifang Hou; Andrea A Baccarelli; Yun Li; Sarah E Harris; Janie Corley; Adele Taylor; Ian J Deary; James D Stewart; Eric A Whitsel; Themistocles L Assimes; Wei Chen; Shengxu Li; Massimo Mangino; Jordana T Bell; James G Wilson; Abraham Aviv; Riccardo E Marioni; Kenneth Raj; Steve Horvath
Journal:  Aging (Albany NY)       Date:  2019-08-18       Impact factor: 5.682

8.  DNA methylation age of human tissues and cell types.

Authors:  Steve Horvath
Journal:  Genome Biol       Date:  2013       Impact factor: 13.583

9.  Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up.

Authors:  Xia Li; Alexander Ploner; Yunzhang Wang; Patrik Ke Magnusson; Chandra Reynolds; Deborah Finkel; Nancy L Pedersen; Juulia Jylhävä; Sara Hägg
Journal:  Elife       Date:  2020-02-11       Impact factor: 8.140

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  1 in total

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

Authors:  James Clement; Qi Yan; Megha Agrawal; Ramon E Coronado; John A Sturges; Markus Horvath; Ake T Lu; Robert T Brooke; Steve Horvath
Journal:  Aging Cell       Date:  2022-09-02       Impact factor: 11.005

  1 in total

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