Familial longevity is marked by enhanced insulin sensitivity

Aging Cell. 2011 Feb;10(1):114-21. doi: 10.1111/j.1474-9726.2010.00650.x. Epub 2010 Dec 7.


Insulin resistance is a risk factor for various age-related diseases. In the Leiden Longevity study, we recruited long-lived siblings and their offspring. Previously, we showed that, compared to controls, the offspring of long-lived siblings had a better glucose tolerance. Here, we compared groups of offspring from long-lived siblings and controls for the relation between insulin and glucose in nonfasted serum (n = 1848 subjects) and for quantitation of insulin action using a two-step hyperinsulinemic-euglycemic clamp (n = 24 subjects). Groups of offspring and controls were similar with regard to sex distribution, age, and body mass index. We observed a positive bi-phasic linear relationship between ln (insulin) levels and nonfasted glucose with a steeper slope from 10.7mU L(-1) insulin onwards in controls compared to offspring (P = 0.02). During the clamp study, higher glucose infusion rate was required to maintain euglycemia during high-dose insulin infusion (P = 0.036) in offspring, reflecting higher whole-body insulin sensitivity. After adjustment for sex, age, and fat mass, the insulin-mediated glucose disposal rate (GDR) was higher in offspring than controls (42.5 ± 2.7 vs. 33.2 ± 2.7 micromol kg(-1) min(-1) , mean ± SE, P = 0.025). The insulin-mediated suppression of endogenous glucose production and lipolysis did not differ between groups (all P > 0.05). Furthermore, GDR was significantly correlated with the mean age of death of the parents. In conclusion, offspring from long-lived siblings are marked by enhanced peripheral glucose disposal. Future research will focus on identifying the underlying biomolecular mechanisms, with the aim to promote health in old age.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Children
  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis
  • Body Composition / physiology
  • Body Mass Index
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glucose / administration & dosage
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Humans
  • Infusions, Intravenous
  • Insulin / administration & dosage
  • Insulin / blood*
  • Insulin / metabolism*
  • Insulin Resistance / physiology*
  • Lipolysis / physiology
  • Liver / metabolism
  • Longevity / physiology*
  • Male
  • Middle Aged
  • Netherlands
  • Risk Factors


  • Blood Glucose
  • Insulin
  • Glucose