Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production

Abstract

Calorie restriction (CR) slows aging and is thought to improve insulin sensitivity in laboratory animals. In contrast, decreased insulin signaling and/or mild insulin resistance paradoxically extends maximal lifespan in various genetic animal models of longevity. Nothing is known regarding the long-term effects of CR on glucose tolerance and insulin action in lean healthy humans. In this study we evaluated body composition, glucose, and insulin responses to an oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had been eating a CR diet for an average of 6.9±5.5 years, (mean age 53.0±11 years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28 age-and sex-matched sedentary controls eating Western diets (WD). We found that the CR and EX volunteers were significantly leaner than the WD volunteers. Insulin sensitivity, determined according to the HOMA-IR and the Matsuda and DeFronzo insulin sensitivity indexes, was significantly higher in the CR and EX groups than in the WD group (P=0.001). Nonetheless, despite high serum adiponectin and low inflammation, ∼40% of CR individuals exhibited an exaggerated hyperglycemic response to a glucose load. This impaired glucose tolerance is associated with lower circulating levels of IGF-1, total testosterone, and triiodothyronine, which are typical adaptations to life-extending CR in rodents.

Impaired quality control of mitochondria: Aging from a new perspective

“…However, the exact contribution of ROS and ROS scavenging pathways on longevity after physical training are difficult to assess since also other factors come into play; e.g. calorie intake/restriction and increased insulin sensitivity (Fontana et al, 2009;Lanza et al, 2008).…”

Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity

“…Regular physical activity has been demonstrated to improve glucose and lipid homeostasis, maintain muscle mass, and delay aging. [12][13][14][15][16][17] For instance, 5 mo of exercise training are sufficient to completely reverse the premature aging phenotype of the mitochondrial DNA mutator mice, which possess a dysfunctional copy of the mitochondrial proofreading-exonuclease, POLG (poly[A] polymerase gamma). 18 Although the positive effects of exercise are undisputed, the underlying mechanisms are still under vigorous investigation.…”

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

“…30 Indeed, it has been widely accepted that the CR-related downregulation of the insulin/IGF-1 pathway is one of the key factors by which CR increases maximal and mean life span in rodents. 31,32 Paradoxically, the brain tends to benefit from IGF-1 signaling, including neurogenesis. 33,34 However, the findings of a recent report suggest that IGF-1 could have beneficial as well as harmful effects on the developing brain.…”