Lean Mass, Muscle Strength and Gene Expression in Community Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS)

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.

Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-γ expression in nonobese Type 2 diabetic rats

“…Although observational human studies support a link between vitamin D status and Vitamin D deficiency is also reported to be associated with the loss of skeletal muscle mass and strength especially in the elderly [32,33], but no intervention trials have been performed to determine the impact of vitamin D supplementation on body composition in humans. The present study found that vitamin D sufficiency preserved lean body mass that was lower in vitamin D deficient rats and intermediate with excessive vitamin D supplementation.…”

Relationship between hand grip strength and peak VO2 in community‐dwelling elderly outpatients

“…A previous study suggested that myostatin, which is one of the factors in the ubiquitin proteasome system, might be a potential mechanism of this triangle association. First, higher serum myostatin is associated with lower HGS [21], and lower myostatin is associated with higher HGS [22].…”

Myeloid cell‐derived tumor necrosis factor‐alpha promotes sarcopenia and regulates muscle cell fusion with aging muscle fibers

“…Sarcopenia is also associated with decreased muscle regenerative capacity that can further exacerbate loss of function. Together, these changes lead to increased risk of falling, loss of physical independence, and increased morbidity and mortality (Landi et al, 2012; Patel et al, 2014; Xue, Walston, Fried, & Beamer, 2011). Although sarcopenia is influenced by intrinsic changes in muscle (Sousa‐Victor et al, 2014) and by extrinsic factors from other systems (Carlson & Faulkner, 1989; Fry et al, 2015), the specific mechanisms that drive sarcopenia are largely unknown.…”