Evaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8, and Their Binding Proteins, Follistatin and Follistatin-Like Protein-3, With Measures of Skeletal Muscle Mass, Muscle Strength, and Physical Function in Older Adults.


Journal

The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837

Informations de publication

Date de publication:
28 10 2023
Historique:
received: 17 08 2022
pmc-release: 08 02 2024
medline: 30 10 2023
pubmed: 9 2 2023
entrez: 8 2 2023
Statut: ppublish

Résumé

Based on studies from animal models, growth differentiation factor-11 (GDF-11) may have rejuvenating effects in humans. GDF-11 has high sequence homology with GDF-8 (also known as myostatin); follistatin and follistatin-like protein-3 (FSTL-3) are inhibitory proteins of both GDF-8 and GDF-11. Using highly specific liquid chromatography with tandem mass spectrometry assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL-3, we quantified the association of these factors with muscle size, strength, and physical performance in 2 prospective cohort studies of community-dwelling older adults (Health, Aging, and Body Composition study [Health ABC] and Cardiovascular Health Study [CHS]). GDF-8 levels were positively associated with thigh muscle cross-sectional area and density in Health ABC (data not available in CHS). GDF-8 levels were positively associated with lean mass (a surrogate of muscle mass) in Health ABC but not CHS, and grip strength in CHS but not Health ABC. FSTL-3 (and perhaps follistatin) was negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance. GDF-8 and its binding proteins, follistatin and FSTL-3, may constitute a counterregulatory system (chalones) to restrain age-related loss of muscle mass and strength.

Sections du résumé

BACKGROUND
Based on studies from animal models, growth differentiation factor-11 (GDF-11) may have rejuvenating effects in humans. GDF-11 has high sequence homology with GDF-8 (also known as myostatin); follistatin and follistatin-like protein-3 (FSTL-3) are inhibitory proteins of both GDF-8 and GDF-11.
METHODS
Using highly specific liquid chromatography with tandem mass spectrometry assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL-3, we quantified the association of these factors with muscle size, strength, and physical performance in 2 prospective cohort studies of community-dwelling older adults (Health, Aging, and Body Composition study [Health ABC] and Cardiovascular Health Study [CHS]).
RESULTS
GDF-8 levels were positively associated with thigh muscle cross-sectional area and density in Health ABC (data not available in CHS). GDF-8 levels were positively associated with lean mass (a surrogate of muscle mass) in Health ABC but not CHS, and grip strength in CHS but not Health ABC. FSTL-3 (and perhaps follistatin) was negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance.
CONCLUSIONS
GDF-8 and its binding proteins, follistatin and FSTL-3, may constitute a counterregulatory system (chalones) to restrain age-related loss of muscle mass and strength.

Identifiants

pubmed: 36752218
pii: 7031089
doi: 10.1093/gerona/glad045
pmc: PMC10613016
doi:

Substances chimiques

Myostatin 0
Carrier Proteins 0
Follistatin 0
Growth Differentiation Factors 0
Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Intramural Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2051-2059

Subventions

Organisme : NIA NIH HHS
ID : R01 AG052964
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL080295
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL130114
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023629
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG053325
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200036C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200800007C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC55222
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85079
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85080
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85081
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85082
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85083
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85086
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00006
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG028050
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR012459
Pays : United States

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Peggy M Cawthon (PM)

Research Institute, California Pacific Medical Center, San Francisco, California,USA.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

Sheena Patel (S)

Research Institute, California Pacific Medical Center, San Francisco, California,USA.

Anne B Newman (AB)

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania,USA.

Shalender Bhasin (S)

Research Program in Men's Health: Aging and Metabolism; Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Liming Peng (L)

Research Program in Men's Health: Aging and Metabolism; Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Russell P Tracy (RP)

Department of Pathology and Laboratory Medicine, University of Vermont Larner College of Medicine, Burlington, Vermont,USA.

Jorge R Kizer (JR)

Cardiology Section, San Francisco Veterans Affairs Health Care System, and Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California,USA.

Se-Jin Lee (SJ)

The Jackson Laboratory and University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Luigi Ferrucci (L)

Office of the Scientific Director, National Institute on Aging, Bethesda, Maryland,USA.

Peter Ganz (P)

Cardiology Division, Zuckerberg San Francisco General Hospital and Department of Medicine, University of California San Francisco, San Francisco, California,USA.

Nathan K LeBrasseur (NK)

Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota, USA.

Steven R Cummings (SR)

Research Institute, California Pacific Medical Center, San Francisco, California,USA.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

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Classifications MeSH