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Lean mass, muscle strength and gene expression in community dwelling older men: findings from the Hertfordshire Sarcopenia Study (HSS)

Lean mass, muscle strength and gene expression in community dwelling older men: findings from the Hertfordshire Sarcopenia Study (HSS)
Lean mass, muscle strength and gene expression in community dwelling older men: findings from the Hertfordshire Sarcopenia Study (HSS)
Sarcopenia is associated with adverse health outcomes. This study investigated whether skeletal muscle gene expression was associated with lean mass and grip strength in community-dwelling older men. Utilising a cross-sectional study design, lean muscle mass and grip strength were measured in 88 men aged 68–76 years. Expression profiles of 44 genes implicated in the cellular regulation of skeletal muscle were determined. Serum was analysed for circulating cytokines TNF (tumour necrosis factor), IL-6 (interleukin 6, IFNG (interferon gamma), IL1R1 (interleukin-1 receptor-1). Relationships between skeletal muscle gene expression, circulating cytokines, lean mass and grip strength were examined. Participant groups with higher and lower values of lean muscle mass (n = 18) and strength (n = 20) were used in the analysis of gene expression fold change. Expression of VDR (vitamin D receptor) [fold change (FC) 0.52, standard error for fold change (SE) ± 0.08, p = 0.01] and IFNG mRNA (FC 0.31; SE ± 0.19, p = 0.01) were lower in those with higher lean mass. Expression of IL-6 (FC 0.43; SE ± 0.13, p = 0.02), TNF (FC 0.52; SE ± 0.10, p = 0.02), IL1R1 (FC 0.63; SE ± 0.09, p = 0.04) and MSTN (myostatin) (FC 0.64; SE ± 0.11, p = 0.04) were lower in those with higher grip strength. No other significant changes were observed. Significant negative correlations between serum IL-6 (R = −0.29, p = 0.005), TNF (R = −0.24, p = 0.017) and grip strength were demonstrated. This novel skeletal muscle gene expression study carried out within a well-characterized epidemiological birth cohort has demonstrated that lower expression of VDR and IFNG is associated with higher lean mass, and lower expression of IL-6, TNF, IL1R1 and myostatin is associated with higher grip strength. These findings are consistent with a role of proinflammatory factors in mediating lower muscle strength in community-dwelling older men.
0171-967X
308–316
Patel, Harnish
e1c0826f-d14e-49f3-8049-5b945d185523
Al-Shanti, Nasser
40b85ff8-426f-4a34-bbab-2342d33efa58
Davies, Lucy C.
a45d8083-28ec-4d43-9037-616fd5cddb07
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
Grounds, Miranda D.
999ef050-a029-4846-b429-299dbee7b21c
Tellam, Ross L.
dcc4774e-f2dd-4365-909a-692b54636c58
Stewart, Claire E.
660a4d55-8e52-4312-9df7-3e83421b0bf9
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Aihie Sayer, Avan
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb
Patel, Harnish
e1c0826f-d14e-49f3-8049-5b945d185523
Al-Shanti, Nasser
40b85ff8-426f-4a34-bbab-2342d33efa58
Davies, Lucy C.
a45d8083-28ec-4d43-9037-616fd5cddb07
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
Grounds, Miranda D.
999ef050-a029-4846-b429-299dbee7b21c
Tellam, Ross L.
dcc4774e-f2dd-4365-909a-692b54636c58
Stewart, Claire E.
660a4d55-8e52-4312-9df7-3e83421b0bf9
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Aihie Sayer, Avan
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb

Patel, Harnish, Al-Shanti, Nasser, Davies, Lucy C., Barton, Sheila, Grounds, Miranda D., Tellam, Ross L., Stewart, Claire E., Cooper, Cyrus and Aihie Sayer, Avan (2014) Lean mass, muscle strength and gene expression in community dwelling older men: findings from the Hertfordshire Sarcopenia Study (HSS). Calcified Tissue International, 308–316.

Record type: Article

Abstract

Sarcopenia is associated with adverse health outcomes. This study investigated whether skeletal muscle gene expression was associated with lean mass and grip strength in community-dwelling older men. Utilising a cross-sectional study design, lean muscle mass and grip strength were measured in 88 men aged 68–76 years. Expression profiles of 44 genes implicated in the cellular regulation of skeletal muscle were determined. Serum was analysed for circulating cytokines TNF (tumour necrosis factor), IL-6 (interleukin 6, IFNG (interferon gamma), IL1R1 (interleukin-1 receptor-1). Relationships between skeletal muscle gene expression, circulating cytokines, lean mass and grip strength were examined. Participant groups with higher and lower values of lean muscle mass (n = 18) and strength (n = 20) were used in the analysis of gene expression fold change. Expression of VDR (vitamin D receptor) [fold change (FC) 0.52, standard error for fold change (SE) ± 0.08, p = 0.01] and IFNG mRNA (FC 0.31; SE ± 0.19, p = 0.01) were lower in those with higher lean mass. Expression of IL-6 (FC 0.43; SE ± 0.13, p = 0.02), TNF (FC 0.52; SE ± 0.10, p = 0.02), IL1R1 (FC 0.63; SE ± 0.09, p = 0.04) and MSTN (myostatin) (FC 0.64; SE ± 0.11, p = 0.04) were lower in those with higher grip strength. No other significant changes were observed. Significant negative correlations between serum IL-6 (R = −0.29, p = 0.005), TNF (R = −0.24, p = 0.017) and grip strength were demonstrated. This novel skeletal muscle gene expression study carried out within a well-characterized epidemiological birth cohort has demonstrated that lower expression of VDR and IFNG is associated with higher lean mass, and lower expression of IL-6, TNF, IL1R1 and myostatin is associated with higher grip strength. These findings are consistent with a role of proinflammatory factors in mediating lower muscle strength in community-dwelling older men.

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Gene expression in older men CTI revised manuscript 190614 HP final for eprints soton - Accepted Manuscript
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e-pub ahead of print date: 24 July 2014
Published date: October 2014

Identifiers

Local EPrints ID: 424544
URI: http://eprints.soton.ac.uk/id/eprint/424544
ISSN: 0171-967X
PURE UUID: 48d09cb9-a548-4fa4-8e06-b3f21f781337
ORCID for Harnish Patel: ORCID iD orcid.org/0000-0002-0081-1802
ORCID for Sheila Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 05 Oct 2018 11:38
Last modified: 23 Nov 2021 02:40

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Contributors

Author: Harnish Patel ORCID iD
Author: Nasser Al-Shanti
Author: Lucy C. Davies
Author: Sheila Barton ORCID iD
Author: Miranda D. Grounds
Author: Ross L. Tellam
Author: Claire E. Stewart
Author: Cyrus Cooper ORCID iD
Author: Avan Aihie Sayer

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