Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats

Aging is a degenerative process involving cell function deterioration, leading to altered metabolic pathways, increased metabolite diversity, and dysregulated metabolism. Previously, we reported that human placenta-derived mesenchymal stem cells (hPD-MSCs) have therapeutic effects on ovarian aging....

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Main Authors: Kyeoung-Hwa Kim, Kyung-Ah Lee
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/1/566
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author Kyeoung-Hwa Kim
Kyung-Ah Lee
author_facet Kyeoung-Hwa Kim
Kyung-Ah Lee
author_sort Kyeoung-Hwa Kim
collection DOAJ
description Aging is a degenerative process involving cell function deterioration, leading to altered metabolic pathways, increased metabolite diversity, and dysregulated metabolism. Previously, we reported that human placenta-derived mesenchymal stem cells (hPD-MSCs) have therapeutic effects on ovarian aging. This study aimed to identify hPD-MSC therapy-induced responses at the metabolite and protein levels and serum biomarker(s) of aging and/or rejuvenation. We observed weight loss after hPD-MSC therapy. Importantly, insulin-like growth factor-I (IGF-I), known prolongs healthy life spans, were markedly elevated in serum. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) analysis identified 176 metabolites, among which the levels of 3-hydroxybutyric acid, glycocholic acid, and taurine, which are associated with health and longevity, were enhanced after hPD-MSC stimulation. Furthermore, after hPD-MSC therapy, the levels of vitamin B6 and its metabolite pyridoxal 5′-phosphate were markedly increased in the serum and liver, respectively. Interestingly, hPD-MSC therapy promoted serotonin production due to increased vitamin B6 metabolism rates. Increased liver serotonin levels after multiple-injection therapy altered the expression of mRNAs and proteins associated with hepatocyte proliferation and mitochondrial biogenesis. Changes in metabolites in circulation after hPD-MSC therapy can be used to identify biomarker(s) of aging and/or rejuvenation. In addition, serotonin is a valuable therapeutic target for reversing aging-associated liver degeneration.
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spelling doaj.art-6e3d9848d6d64f9cb8f879c1576870ff2023-11-23T11:41:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123156610.3390/ijms23010566Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female RatsKyeoung-Hwa Kim0Kyung-Ah Lee1Department of Biomedical Science, Institute of Reproductive Medicine, College of Life Science, CHA University, Pangyo-ro 335, Seongnam-si 13488, Gyeonggi-do, KoreaDepartment of Biomedical Science, Institute of Reproductive Medicine, College of Life Science, CHA University, Pangyo-ro 335, Seongnam-si 13488, Gyeonggi-do, KoreaAging is a degenerative process involving cell function deterioration, leading to altered metabolic pathways, increased metabolite diversity, and dysregulated metabolism. Previously, we reported that human placenta-derived mesenchymal stem cells (hPD-MSCs) have therapeutic effects on ovarian aging. This study aimed to identify hPD-MSC therapy-induced responses at the metabolite and protein levels and serum biomarker(s) of aging and/or rejuvenation. We observed weight loss after hPD-MSC therapy. Importantly, insulin-like growth factor-I (IGF-I), known prolongs healthy life spans, were markedly elevated in serum. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) analysis identified 176 metabolites, among which the levels of 3-hydroxybutyric acid, glycocholic acid, and taurine, which are associated with health and longevity, were enhanced after hPD-MSC stimulation. Furthermore, after hPD-MSC therapy, the levels of vitamin B6 and its metabolite pyridoxal 5′-phosphate were markedly increased in the serum and liver, respectively. Interestingly, hPD-MSC therapy promoted serotonin production due to increased vitamin B6 metabolism rates. Increased liver serotonin levels after multiple-injection therapy altered the expression of mRNAs and proteins associated with hepatocyte proliferation and mitochondrial biogenesis. Changes in metabolites in circulation after hPD-MSC therapy can be used to identify biomarker(s) of aging and/or rejuvenation. In addition, serotonin is a valuable therapeutic target for reversing aging-associated liver degeneration.https://www.mdpi.com/1422-0067/23/1/566agingantiagingstem cell therapymetabolismpredictor of rejuvenationserotonin
spellingShingle Kyeoung-Hwa Kim
Kyung-Ah Lee
Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
International Journal of Molecular Sciences
aging
antiaging
stem cell therapy
metabolism
predictor of rejuvenation
serotonin
title Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
title_full Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
title_fullStr Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
title_full_unstemmed Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
title_short Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
title_sort metabolic rewiring by human placenta derived mesenchymal stem cell therapy promotes rejuvenation in aged female rats
topic aging
antiaging
stem cell therapy
metabolism
predictor of rejuvenation
serotonin
url https://www.mdpi.com/1422-0067/23/1/566
work_keys_str_mv AT kyeounghwakim metabolicrewiringbyhumanplacentaderivedmesenchymalstemcelltherapypromotesrejuvenationinagedfemalerats
AT kyungahlee metabolicrewiringbyhumanplacentaderivedmesenchymalstemcelltherapypromotesrejuvenationinagedfemalerats