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Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults

BACKGROUND: A striking effect of old age is the involuntary loss of muscle mass and strength leading to sarcopenia and reduced physiological functions. However, effects of heavy-load exercise in older adults on diseases and functions as predicted by changes in muscle gene expression have been inadeq...

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Autores principales: Gautvik, Kaare M., Olstad, Ole K., Raue, Ulrika, Gautvik, Vigdis T., Kvernevik, Karl J., Utheim, Tor P., Ravnum, Solveig, Kirkegaard, Camilla, Wiig, Håvard, Jones, Garan, Pilling, Luke C., Trappe, Scott, Raastad, Truls, Reppe, Sjur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526277/
https://www.ncbi.nlm.nih.gov/pubmed/36182918
http://dx.doi.org/10.1186/s11556-022-00304-1
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author Gautvik, Kaare M.
Olstad, Ole K.
Raue, Ulrika
Gautvik, Vigdis T.
Kvernevik, Karl J.
Utheim, Tor P.
Ravnum, Solveig
Kirkegaard, Camilla
Wiig, Håvard
Jones, Garan
Pilling, Luke C.
Trappe, Scott
Raastad, Truls
Reppe, Sjur
author_facet Gautvik, Kaare M.
Olstad, Ole K.
Raue, Ulrika
Gautvik, Vigdis T.
Kvernevik, Karl J.
Utheim, Tor P.
Ravnum, Solveig
Kirkegaard, Camilla
Wiig, Håvard
Jones, Garan
Pilling, Luke C.
Trappe, Scott
Raastad, Truls
Reppe, Sjur
author_sort Gautvik, Kaare M.
collection PubMed
description BACKGROUND: A striking effect of old age is the involuntary loss of muscle mass and strength leading to sarcopenia and reduced physiological functions. However, effects of heavy-load exercise in older adults on diseases and functions as predicted by changes in muscle gene expression have been inadequately studied. METHODS: Thigh muscle global transcriptional activity (transcriptome) was analyzed in cohorts of older and younger adults before and after 12–13 weeks heavy-load strength exercise using Affymetrix microarrays. Three age groups, similarly trained, were compared: younger adults (age 24 ± 4 years), older adults of average age 70 years (Oslo cohort) and above 80 years (old BSU cohort). To increase statistical strength, one of the older cohorts was used for validation. Ingenuity Pathway analysis (IPA) was used to identify predicted biological effects of a gene set that changed expression after exercise, and Principal Component Analysis (PCA) was used to visualize differences in muscle gene expressen between cohorts and individual participants as well as overall changes upon exercise. RESULTS: Younger adults, showed few transcriptome changes, but a marked, significant impact was observed in persons of average age 70 years and even more so in persons above 80 years. The 249 transcripts positively or negatively altered in both cohorts of older adults (q-value < 0.1) were submitted to gene set enrichment analysis using IPA. The transcripts predicted increase in several aspects of “vascularization and muscle contractions”, whereas functions associated with negative health effects were reduced, e.g., “Glucose metabolism disorder” and “Disorder of blood pressure”. Several genes that changed expression after intervention were confirmed at the genome level by containing single nucleotide variants associated with handgrip strength and muscle expression levels, e.g., CYP4B1 (p = 9.2E-20), NOTCH4 (p = 9.7E-8), and FZD4 (p = 5.3E-7). PCA of the 249 genes indicated a differential pattern of muscle gene expression in young and elderly. However, after exercise the expression patterns in both young and old BSU cohorts were changed in the same direction for the vast majority of participants. CONCLUSIONS: The positive impact of heavy-load strength training on the transcriptome increased markedly with age. The identified molecular changes translate to improved vascularization and muscular strength, suggesting highly beneficial health effects for older adults. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11556-022-00304-1.
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spelling pubmed-95262772022-10-02 Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults Gautvik, Kaare M. Olstad, Ole K. Raue, Ulrika Gautvik, Vigdis T. Kvernevik, Karl J. Utheim, Tor P. Ravnum, Solveig Kirkegaard, Camilla Wiig, Håvard Jones, Garan Pilling, Luke C. Trappe, Scott Raastad, Truls Reppe, Sjur Eur Rev Aging Phys Act Research Article BACKGROUND: A striking effect of old age is the involuntary loss of muscle mass and strength leading to sarcopenia and reduced physiological functions. However, effects of heavy-load exercise in older adults on diseases and functions as predicted by changes in muscle gene expression have been inadequately studied. METHODS: Thigh muscle global transcriptional activity (transcriptome) was analyzed in cohorts of older and younger adults before and after 12–13 weeks heavy-load strength exercise using Affymetrix microarrays. Three age groups, similarly trained, were compared: younger adults (age 24 ± 4 years), older adults of average age 70 years (Oslo cohort) and above 80 years (old BSU cohort). To increase statistical strength, one of the older cohorts was used for validation. Ingenuity Pathway analysis (IPA) was used to identify predicted biological effects of a gene set that changed expression after exercise, and Principal Component Analysis (PCA) was used to visualize differences in muscle gene expressen between cohorts and individual participants as well as overall changes upon exercise. RESULTS: Younger adults, showed few transcriptome changes, but a marked, significant impact was observed in persons of average age 70 years and even more so in persons above 80 years. The 249 transcripts positively or negatively altered in both cohorts of older adults (q-value < 0.1) were submitted to gene set enrichment analysis using IPA. The transcripts predicted increase in several aspects of “vascularization and muscle contractions”, whereas functions associated with negative health effects were reduced, e.g., “Glucose metabolism disorder” and “Disorder of blood pressure”. Several genes that changed expression after intervention were confirmed at the genome level by containing single nucleotide variants associated with handgrip strength and muscle expression levels, e.g., CYP4B1 (p = 9.2E-20), NOTCH4 (p = 9.7E-8), and FZD4 (p = 5.3E-7). PCA of the 249 genes indicated a differential pattern of muscle gene expression in young and elderly. However, after exercise the expression patterns in both young and old BSU cohorts were changed in the same direction for the vast majority of participants. CONCLUSIONS: The positive impact of heavy-load strength training on the transcriptome increased markedly with age. The identified molecular changes translate to improved vascularization and muscular strength, suggesting highly beneficial health effects for older adults. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11556-022-00304-1. BioMed Central 2022-10-01 /pmc/articles/PMC9526277/ /pubmed/36182918 http://dx.doi.org/10.1186/s11556-022-00304-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Gautvik, Kaare M.
Olstad, Ole K.
Raue, Ulrika
Gautvik, Vigdis T.
Kvernevik, Karl J.
Utheim, Tor P.
Ravnum, Solveig
Kirkegaard, Camilla
Wiig, Håvard
Jones, Garan
Pilling, Luke C.
Trappe, Scott
Raastad, Truls
Reppe, Sjur
Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults
title Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults
title_full Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults
title_fullStr Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults
title_full_unstemmed Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults
title_short Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults
title_sort heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526277/
https://www.ncbi.nlm.nih.gov/pubmed/36182918
http://dx.doi.org/10.1186/s11556-022-00304-1
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