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Targeted proteomics of appendicular skeletal muscle mass and handgrip strength in Black South Africans: a cross-sectional study

Targeted proteomics of appendicular skeletal muscle mass and handgrip strength in Black South Africans: a cross-sectional study
Targeted proteomics of appendicular skeletal muscle mass and handgrip strength in Black South Africans: a cross-sectional study
Although appendicular skeletal muscle mass (ASM) and handgrip strength (HGS) are key components of sarcopenia, their underlying biological mechanisms remain poorly understood. We aimed to investigate associations of circulating biomarkers with ASM and HGS in middle-aged black South Africans. This study consisted of 934 black South Africans (469 men and 465 women, aged 41–72 years) from the Middle-aged Soweto cohort. Linear regression models were used to examine relationships between 182 biomarkers (measured with proximity extension assay) and dual-energy X-ray absorptiometry-measured ASM and dynamometer-measured HGS. Age, height, sex, smoking, alcohol, food insecurity, physical activity, visceral adipose tissue, HIV and menopausal status were included as confounders. Regression models showing sex-interactions were stratified by sex. The Benjamini–Hochberg false discovery rate (FDR) was used to control for multiple testing, and FDR-adjusted P values were reported. In the total sample, 10 biomarkers were associated with higher ASM and 29 with lower ASM (P < 0.05). Out of these 39 biomarkers, 8 were also associated with lower HGS (P < 0.05). MMP-7 was associated with lower HGS only (P = 0.011) in the total sample. Sex-interactions (P < 0.05) were identified for 52 biomarkers for ASM, and 6 for HGS. For men, LEP, MEPE and SCF were associated with higher ASM (P < 0.001, = 0.004, = 0.006, respectively), and MEPE and SCF were also associated with higher HGS (P = 0.001, 0.012, respectively). Also in men, 37 biomarkers were associated with lower ASM (P < 0.05), with none of these being associated with lower HGS. Furthermore, DLK-1 and MYOGLOBIN were associated with higher HGS only (P = 0.004, 0.006, respectively), while GAL-9 was associated with lower HGS only (P = 0.005), among men. For women, LEP, CD163, IL6, TNF-R1 and TNF-R2 were associated with higher ASM (P < 0.001, = 0.014, = 0.027, = 0.014, = 0.048, respectively), while IGFBP-2, CTRC and RAGE were associated with lower ASM (P = 0.043, 0.001, 0.014, respectively). No biomarker was associated with HGS in women. In conclusion, most biomarkers were associated with ASM and not HGS, and the associations of biomarkers with ASM and HGS displayed sex-specificity in middle-aged black South Africans. Proteomic studies should examine ASM and HGS individually. Future research should also consider sexual dimorphism in the pathophysiology of sarcopenia for development of sex-specific treatment and diagnostic methods.

Introduction
2045-2322
Dlamini, Siphiwe N.
af5d00d3-f69d-47ab-84a8-27b535a9bfd4
Norris, Shane
1d346f1b-6d5f-4bca-ac87-7589851b75a4
Mendham, Amy E.
63f08952-baa4-42cc-b472-02462cd3026d
Mtintsilana, Asanda
a90fe207-619f-4f4a-9526-e6d522b87968
Ward, Kate
39bd4db1-c948-4e32-930e-7bec8deb54c7
Olsson, Tommy
e5e874c9-7e53-492c-a46d-b4918e0d38ea
Goedecke, Julia H.
27db2aa1-04c2-44e8-9c0e-e9bbe98f2e25
Micklesfield, Lisa K.
e73dd95b-ce79-4dc4-b0be-a8935eb069c8
Dlamini, Siphiwe N.
af5d00d3-f69d-47ab-84a8-27b535a9bfd4
Norris, Shane
1d346f1b-6d5f-4bca-ac87-7589851b75a4
Mendham, Amy E.
63f08952-baa4-42cc-b472-02462cd3026d
Mtintsilana, Asanda
a90fe207-619f-4f4a-9526-e6d522b87968
Ward, Kate
39bd4db1-c948-4e32-930e-7bec8deb54c7
Olsson, Tommy
e5e874c9-7e53-492c-a46d-b4918e0d38ea
Goedecke, Julia H.
27db2aa1-04c2-44e8-9c0e-e9bbe98f2e25
Micklesfield, Lisa K.
e73dd95b-ce79-4dc4-b0be-a8935eb069c8

Dlamini, Siphiwe N., Norris, Shane, Mendham, Amy E., Mtintsilana, Asanda, Ward, Kate, Olsson, Tommy, Goedecke, Julia H. and Micklesfield, Lisa K. (2022) Targeted proteomics of appendicular skeletal muscle mass and handgrip strength in Black South Africans: a cross-sectional study. Scientific Reports, 12 (1), [9512]. (doi:10.1038/s41598-022-13548-9).

Record type: Article

Abstract

Although appendicular skeletal muscle mass (ASM) and handgrip strength (HGS) are key components of sarcopenia, their underlying biological mechanisms remain poorly understood. We aimed to investigate associations of circulating biomarkers with ASM and HGS in middle-aged black South Africans. This study consisted of 934 black South Africans (469 men and 465 women, aged 41–72 years) from the Middle-aged Soweto cohort. Linear regression models were used to examine relationships between 182 biomarkers (measured with proximity extension assay) and dual-energy X-ray absorptiometry-measured ASM and dynamometer-measured HGS. Age, height, sex, smoking, alcohol, food insecurity, physical activity, visceral adipose tissue, HIV and menopausal status were included as confounders. Regression models showing sex-interactions were stratified by sex. The Benjamini–Hochberg false discovery rate (FDR) was used to control for multiple testing, and FDR-adjusted P values were reported. In the total sample, 10 biomarkers were associated with higher ASM and 29 with lower ASM (P < 0.05). Out of these 39 biomarkers, 8 were also associated with lower HGS (P < 0.05). MMP-7 was associated with lower HGS only (P = 0.011) in the total sample. Sex-interactions (P < 0.05) were identified for 52 biomarkers for ASM, and 6 for HGS. For men, LEP, MEPE and SCF were associated with higher ASM (P < 0.001, = 0.004, = 0.006, respectively), and MEPE and SCF were also associated with higher HGS (P = 0.001, 0.012, respectively). Also in men, 37 biomarkers were associated with lower ASM (P < 0.05), with none of these being associated with lower HGS. Furthermore, DLK-1 and MYOGLOBIN were associated with higher HGS only (P = 0.004, 0.006, respectively), while GAL-9 was associated with lower HGS only (P = 0.005), among men. For women, LEP, CD163, IL6, TNF-R1 and TNF-R2 were associated with higher ASM (P < 0.001, = 0.014, = 0.027, = 0.014, = 0.048, respectively), while IGFBP-2, CTRC and RAGE were associated with lower ASM (P = 0.043, 0.001, 0.014, respectively). No biomarker was associated with HGS in women. In conclusion, most biomarkers were associated with ASM and not HGS, and the associations of biomarkers with ASM and HGS displayed sex-specificity in middle-aged black South Africans. Proteomic studies should examine ASM and HGS individually. Future research should also consider sexual dimorphism in the pathophysiology of sarcopenia for development of sex-specific treatment and diagnostic methods.

Introduction

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Accepted/In Press date: 25 May 2022
e-pub ahead of print date: 9 June 2022

Identifiers

Local EPrints ID: 457873
URI: http://eprints.soton.ac.uk/id/eprint/457873
ISSN: 2045-2322
PURE UUID: 6209985e-bbab-4402-a328-d5e094744723
ORCID for Shane Norris: ORCID iD orcid.org/0000-0001-7124-3788
ORCID for Kate Ward: ORCID iD orcid.org/0000-0001-7034-6750

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Date deposited: 21 Jun 2022 18:07
Last modified: 11 Nov 2022 02:55

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Contributors

Author: Siphiwe N. Dlamini
Author: Shane Norris ORCID iD
Author: Amy E. Mendham
Author: Asanda Mtintsilana
Author: Kate Ward ORCID iD
Author: Tommy Olsson
Author: Julia H. Goedecke
Author: Lisa K. Micklesfield

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