Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons

Abstract

Deregulation of the inflammatory response plays a major role in the age-related decline of physical performance. The causal pathway leading from inflammation to disability has not been fully clarified, but several researches suggest that interleukin-6 (IL-6) causes a reduction of physical performance in elderly through its effect on muscle function. In vitro studies demonstrated that IL-6 inhibits the secretion of insulin-like growth factor I (IGF-I) and its biological activity, suggesting that the negative effect of IL-6 on muscle function might be mediated through IGF-I. We evaluated the joint effect of IGF-I and IL-6 on muscle function in a population-based sample of 526 persons with a wide age range (20–102 yr). After adjusting for potential confounders, such as age, sex, body mass index, IL-6 receptor, and IL-6 promoter polymorphism, IL-6, IGF-I, and their interaction were significant predictors of handgrip and muscle power. In analyses stratified by IL-6 tertiles, IGF-I was an independent predictor of muscle function only in subjects in the lowest IL-6 tertile, suggesting that the effect of IGF-I on muscle function depends on IL-6 levels. This mechanism may explain why IL-6 is a strong risk factor for disability.

Muscle strength but not functional capacity is associated with plasma interleukin-6 levels of community-dwelling elderly women

“…A number of studies have demonstrated that chronically high IL-6 plasma levels in the elderly reduce muscle mass and strength (13,17,18,27) but not in communitydwelling health elderly women. This is the first Brazilian study to investigate whether IL-6 levels are associated with muscle performance and functional capacity in community-dwelling elderly women.…”

“…A number of epidemiological studies have reported an association between high levels of IL-6 and the loss of functional capacity, as well as an increase in mortality rates for elderly people (10,(13)(14)(15)(16). Other studies have demonstrated an association between high levels of IL-6 and reduced muscle strength in the elderly (13,17,18). Haddad et al (19) found atrophy in the tibialis anterior muscle of mice injected locally with relatively low doses of IL-6.…”

Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle

“…The inflammatory marker IL-6, which is associated with sarcopaenia and muscle wasting [18], was elevated in the old rats (P \ 0.05), but was not significantly elevated further after treatment with alfacalcidol. The adiponectin serum concentration was 64% higher in the alfacalcidol group compared to that of the vehicle group (P = 0.004), but was not significantly different from that of the control adult group.…”

“…IL-6 is an inflammatory cytokine and elevated circulating levels have been associated with loss of muscle strength [18,49] and atrophy [42,47]. Treatment with alfacalcidol was, however, not accompanied with an increase in circulating IL-6 levels and alfacalcidol has even been shown to decrease tumor necrosis factor-a [50], another cytokine having a catabolic effect on muscle [42].…”

“…Adiponectin, on the other hand, plays a role in the regulation of metabolism and is inversely related to the amount of body fat [15,16]. Elevated levels of interleukin 6 (IL-6) may also reduce food intake [17] and contribute to muscle wasting via abolishing the normally anabolic effect of insulin-like growth factor 1 (IGF-1) [18]. The muscle breakdown may be realised by an increased expression of the muscle specific ubiquitin ligases, MAFbx and MuRF-1, that play an important role in protein breakdown, as observed during undernutrition [19][20][21][22] and systemic inflammation [23].…”