Microbial translocation and skeletal muscle in young and old vervet monkeys

Abstract

Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6-27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey's MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging.

Keywords: Endotoxemia; Insulin sensitivity; Intestinal barrier function; Non-human primate; Sarcopenia.

Fig. 1

Older healthy monkeys are sarcopenic. Walking speed was slower (a; n = 51; p < 0.001), and muscle mass was reduced as measured by leg circumference (b; n = 22, p = 0.05) and by CT-determined total lean tissue mass measured from both hind limbs (c; n = 27, p = 0.04) in old monkeys. *p < 0.05, ***p < 0.001

Fig. 2

Microbial translocation biomarkers lipopolysaccharide-binding protein (LBP-1, n = 42; a) and soluble CD14 (sCD14, n = 44; b) positively associate with inflammatory burden as estimated by C-reactive protein concentrations in plasma from healthy, active monkeys

Fig. 3

a Greater microbial translocation as measured by LBP-1 concentrations in the circulation of young and old monkeys is associated with reduced insulin signaling effectiveness in skeletal muscle. b Better insulin sensitivity is associated with greater levels of spontaneous activity in all monkeys (N = 20)