Glucose tolerance and insulin action in healthy centenarians

Abstract

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P< 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.

Calorie restriction: Decelerating mTOR-driven aging from cells to organisms (including humans)

“…28,[84][85][86][87] And it is known that high insulin-sensitivity is a striking marker of centenarians, people who live more than 100 years. 88,89 Insulin sensitivity was strongly associated with longevity in mice. 51,90 It is reasonable to suggest that insulin-sensitivity is a marker of deactivated mTOR.…”

Adipokines and Aging

“…Intriguingly, there is increasing evidence that preservation of insulin action might be one of the common peculiarities of centenarians that help maintain health and function throughout their extremely long life. Paolisso et al were the first to report that glucose tolerance and insulin sensitivity are better preserved in healthy centenarians in comparison to elderly individuals over 75 years of age 33) . A series of crosssectional studies have reproducibly demonstrated that the prevalence of type 2 diabetes, which is closely associated with age-related insulin resistance, is very low among Finnish 34) , Italian 35) , and Japanese centenarians 36) .…”

Rapamycin-induced glucose intolerance: Hunger or starvation diabetes

“…[38][39][40][41][42][43][44][45][46][47][48][49] In contrast, mice deficient for S6K1 are hypersensitive to insulin 50,51 and live longer 52 And insulin sensitivity is associated with longevity in mice 53,54 and humans. 55,56 mTOR-induced insulin resistance was documented in different conditions. For example, nutrients cause TORdependent insulin resistance in rodents and humans.…”