Abstract
Recently, we have shown that compared to controls, long-lived familial nonagenarians (mean age: 93.4 years) from the Leiden Longevity Study displayed a lower mortality rate, and their middle-aged offspring displayed a lower prevalence of cardio-metabolic diseases, including diabetes mellitus. The evolutionarily conserved insulin/IGF-1 signaling (IIS) pathway has been implicated in longevity in model organisms, but its relevance for human longevity has generated much controversy. Here, we show that compared to their partners, the offspring of familial nonagenarians displayed similar non-fasted serum levels of IGF-1, IGFBP3 and insulin but lower non-fasted serum levels of glucose, indicating that familial longevity is associated with differences in insulin sensitivity.
Highlights
In Western societies, life expectancy has increased dramatically over the last century, but striking interindividual differences in life expectancy remain [1]
We assessed whether the lower glucose levels observed among the group of offspring relative to the group of partners could be driven by differences in IGF1 axis parameters
Consistent with the lower prevalence of diabetes observed earlier, non-fasted serum glucose levels were lower in the offspring of familial nonagenarians when compared to their partners
Summary
In Western societies, life expectancy has increased dramatically over the last century, but striking interindividual differences in life expectancy remain [1]. We have shown that the nonagenarian siblings included in the Leiden Longevity Study displayed a 41% lower risk of mortality compared to sporadic nonagenarians [3]. Compared to their partners, the offspring of nonagenarian siblings displayed a significantly lower prevalence of myocardial infarction, hypertension and diabetes mellitus [3]. The differences in clinical phenotype observed after selection for familial longevity are in line with the lower prevalence of cardio-metabolic disease previously detected when offspring from sporadic centenarians were compared to offspring of parents who had died at average age [4] and when offspring from sporadic centenarians were compared to their partners [5]. The observed lower mortality rate at high ages and better preservation of health at middle age indicates that resilience against disease and death may have similar underlying biological mechanisms that are influenced by genetic or familial factors
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