Short‐term bed rest increases inflammation as evidenced by elevated TLR4, NFκB1 and IL6 expression in skeletal muscle of older adults

Abstract

Aging is characterized by increased systemic and tissue inflammation. However, it is currently unknown if a period of inactivity exacerbates muscle inflammation in older adults. We hypothesized that short‐term bed rest would increase muscle levels of TLR4 and NFκB expression and circulating cytokine levels in older adults. Six healthy, older adults participated in a strict bed rest model for 7 consecutive days. Serum samples and muscle biopsies were taken before and day 7 of bed rest. Serum samples were analyzed for cytokine expression. Muscle samples were analyzed using western blotting and qPCR for TLR4, HSP60, Iκβα protein expression and IL6, NFκB1, IL1β, TNFα, TNFRSA1, SOCS3, IL10, and IL15 mRNA expression. Participants lost ~4% leg lean mass due to bed rest. Additionally, the cytokine, interferon gamma was significant elevated in serum samples after bed rest (P<0.05). In the muscle, TLR4 protein expression and IL6, NFκB1, IL10 and IL15 mRNA expression were increased after bed rest (P<0.05). We conclude that short‐term bed rest increases IL6 expression perhaps through a TLR4/NFκB mechanism, and may contribute to muscle loss observed following a period of bed rest. An increase in the anti‐inflammatory cytokines, IL10 and IL15 may represent a compensatory response to reduce inflammation. Funding: K01AG038556, R01AG018311, R01AR049877, 1UL1RR029876, P30AG024832