Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention

Abstract

Background: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons.

Methods: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured.

Results: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05).

Conclusions: High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.

Keywords: Elderly; Inflammation; Lifestyle interventions; Metabolic hormones; Proinflammatory cytokines; Sarcopenia.

Figure 1

Flowchart for participants' information and blood sampling in the study. Study samples for this study were enrolled from the Peking Union Medical College Hospital (PUMCH) prospective longitudinal sarcopenia study (PPLSS). All sample selection was based on the defined inclusion and exclusion criteria at every step.

Figure 2

The frequency distributions of circulating factors among three EWGSOP subtypes of subjects. The sarcopenic subjects were subdivided based on the EWGSOP criteria. All the circulating factors' data were changed into five‐category histograms, by dividing their ranges into five equal parts, in order to present their frequency distributions. There were no samples for the fourth frequency interval for three circulating factors (IL6, HsCRP, and adiponectin), so only four categories were presented for their histograms. HsCRP, high‐sensitivity C‐reactive protein; IGF1, insulin‐like growth factor 1; IL, interleukin; TNF‐α, tumour necrosis factor α; TWEAK, tumour necrosis factor‐like weak inducer of apoptosis. The graphs were created by SPSS.

Figure 3

Correlation analysis of circulating factor levels vs. limb extremities' muscle mass and muscle strength across all subjects. Correlation value r is adjusted for age, gender, and body mass index. HsCRP, high‐sensitivity C‐reactive protein; IGF1, insulin‐like growth factor 1; IL, interleukin; TNF‐α, tumour necrosis factor α; TWEAK, tumour necrosis factor‐like weak inducer of apoptosis. The graphs were created by photograph.

Figure 4

Changes in key muscle parameters and proinflammatory cytokines after lifestyle intervention. To assess the effects of our intensive lifestyle intervention regimen, we measured (A) limb extremities' muscle mass, (B) grip strength, (C) gait speed, (D) serum TWEAK levels, (E) serum TNF‐α levels, and (F) serum IL‐18 levels. Data are expressed as mean ± standard error of the mean. ^* P < 0.05, ^** P < 0.001 (Mann–Whitney U test). IL, interleukin; TNF‐α, tumour necrosis factor α; TWEAK, tumour necrosis factor‐like weak inducer of apoptosis. The graphs were created by photograph.