Familial longevity is marked by enhanced insulin sensitivity

Abstract

SummaryInsulin resistance is a risk factor for various age-related diseases. In the Leiden Longevity study, we recruited longlived 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 10.7 mU 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 lmol 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.

Gene expression analysis of mTOR pathway: association with human longevity

“…To do this, we took advantage of the Leiden Longevity Study (LLS), a Dutch cohort in which families are selected on the basis of nonagenarian sibling pairs (Schoenmaker et al, 2006). The middle-aged offspring of these nonagenarians have a decreased prevalence of myocardial infarction and type 2 diabetes ) and display healthier intrinsic metabolism reflected by lipid profiles (Barzilai et al, 2001;Heijmans et al, 2006), glucose metabolism and preservation of insulin sensitivity Wijsman et al, 2011) than age-matched controls. They also have different immune profiles in that they fail to show a lower number of CD8+ naive T cells and a higher number of CD8+ late-stage differentiated memory cells dependent on cytomegalovirus infection often seen as a hallmark of immune aging (Derhovanessian et al, 2010).…”

Lower Susceptibility to Cerebral Small Vessel Disease in Human Familial Longevity

“…13 The propensity to become long-lived in the middle-aged to elderly offspring as compared with their spouses is marked by a low incidence of morbidity, beneficial serum levels of lipid and thyroid parameters, preservation of insulin sensitivity, and a lower prevalence of myocardial infarction, hypertension, diabetes mellitus, and use of cardiovascular medication. [14][15][16][17] To study whether the phenotype of human familial longevity also is reflected by a lower susceptibility to cerebral small vessel disease, we investigated whether middle-aged to elderly individuals, who are enriched for familial factors of longevity, have a lower WML load and a lower amount of lacunar infarcts and CMBs compared with their spouses using MRI.…”

Does the longevity of one or both parents influence the health status of their offspring?

“…Recent studies suggest that these observations can be also applied to nonagenarian families. Indeed, data from the Leiden Longevity Study on offspring of nonagenarian siblings indicate a preserved insulin sensitivity, a lower prevalence of myocardial infarction, hypertension, diabetes mellitus and use of cardiovascular medication with respect to their partners (Westendorp et al, 2009;Wijsman et al, 2011).…”