Favorable Glucose Tolerance and Lower Prevalence of Metabolic Syndrome in Offspring without Diabetes Mellitus of Nonagenarian Siblings: The Leiden Longevity Study

Rozing, Maarten P.; Westendorp, Rudi G.J.; Craen, Anton J. M. de; Frölich, Marijke; Goeij, Moniek C.M. de; Heijmans, Bastiaan T.; Beekman, Marian; Wijsman, Carolien A.; Mooijaart, Simon P.; Blauw, G. J.; Slagboom, P. Eline; Heemst, Diana van

doi:10.1111/j.1532-5415.2010.02725.x

Cited by 75 publications

(91 citation statements)

References 26 publications

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“…In contrast to other cross-sectional studies that have included the offspring of centenarians or of nonagenarian siblings [3][4][5][6][7], we applied less rigid criteria to define longevity in the present study. Even having only one parent who had died at age 80 or later was associated with a reduced prevalence of diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic factors may also contribute to better profiles of diabetes risk factors in the offspring of long-lived families: In a rather small study group, the offspring of Ashkenazi Jewish centenarians were shown to have inherited more favourable lipid profiles [15], and a reduced prevalence of hypertension was observed in the offspring of nonagenarian siblings and the offspring of centenarians [4][5][6].…”

Section: Discussionmentioning

confidence: 99%

“…In the Leiden Longevity Study, the offspring of nonagenarian siblings were compared with those of their partners, the offspring displaying a lower prevalence of diabetes, lower levels of fasting glucose, and better glucose tolerance [3,4]. In the offspring of Ashkenazi Jewish centenarians, the prevalence of diabetes was reduced by about 50% compared with the offspring's spouses and other control groups [5].…”

Section: Introductionmentioning

confidence: 99%

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Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study

et al. 2012

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Aims Type 2 diabetes was less prevalent in studies of the offspring of centenarians and a separate study of nonagenarian siblings. We examined whether this reduction would also be found when less extreme criteria of parental longevity (a lifespan of at least 80 years) were applied. Moreover, we looked for an association between parental longevity and incidence of dysglycaemia, which has not yet been reported for a population-based study group. Methods Baseline and 7-year follow-up data on 55-74-year-old participants in the population-based German Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort study were used for the analyses. Participants whose parents had died from traumatic causes were excluded. Diabetes was assessed by validated physician diagnosis or OGTTs. Using logistic regression models, adjusted OR and 95% CIs were calculated for the associations between parental longevity and the prevalence or incidence of dysglycaemia, which was defined as including either type 2 diabetes or prediabetes (defined in this study as comprising impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]). Results In age-and sex-adjusted models, the prevalence of type 2 diabetes was lower in individuals with one (OR 0.63, 95% CI 0.43, 0.93) or two (OR 0.46, 95% CI 0.25, 0.85) long-lived parents. Among participants with normal glucose tolerance at baseline, the odds of incident dysglycaemia were lower in those with one (OR 0.65, 95% CI 0.40, 1.03) or two long-lived parents (OR 0.46, 95% CI 0.22, 0.96) after adjustment for age and sex. Conclusions/interpretation This study showed that longevity of the parents, defined by a lifespan of at least 80 years, was associated with a lower prevalence and incidence of dysglycaemia in their offspring in an older German population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study

et al. 2012

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“…Long-lived men exhibit several biological markers indicative of greater insulin sensitivity, which is associated with the FOXO3A GG genotype (Willcox et al 2008). Also, a favorable glucose metabolism is associated with familial longevity (Rozing et al 2010). Here, we failed to detect any significant association between the two FNDC5 SNPs we studied and EL, suggesting that other factors (e.g., maybe physical activity levels throughout lifespan, nutritional habits or complex gene-environment associations that are yet to be determined) might have a stronger influence on irisinemia, despite the potential functional consequence of at least one of the two SNPs we studied (i.e., rs726344).…”

Section: Discussionmentioning

confidence: 99%

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

Sanchís-Gomar

Garatachea

et al. 2014

AGE

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Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor (FNDC5) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian. It has been recently shown that two single-nucleotide polymorphisms (SNPs) in the FNDC5 gene, rs16835198 and rs726344, are associated with in vivo insulin sensitivity in adults. We determined luciferase gene reporter AGE (2014) 36:9733 DOI 10.1007 Fabian Sanchis-Gomar and Nuria Garatachea contributed equally to this paper activity in the two above-mentioned SNPs and studied genotype distributions among centenarians (n=175, 144 women) and healthy controls (n=347, 142 women) from Spain. We also studied an Italian [79 healthy centenarians (40 women) and 316 healthy controls (156 women)] and a Japanese cohort [742 centenarians (623 women) and 499 healthy controls (356 women)]. The rs726344 SNP had functional significance, as shown by differences in luciferase activity between the constructs of this SNP (all P≤0.05), with the variant A-allele having higher luciferase activity compared with the G-allele (P = 0.04). For the rs16835198 SNP, the variant T-allele tended to show higher luciferase activity compared with the G-allele (P=0.07). However, we found no differences between genotype/allele frequencies of the two SNPs in centenarians versus controls in any cohort, and no significant association (using logistic regression adjusted by sex) between the two SNPs and EL. Further research is needed with different cohorts as well as with additional variants in the FNDC5 gene or in other genes involved in irisin signaling.

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“…Additionally, individuals with outlying cell counts (beyond 3 SDs below or above the standard error of the mean) were excluded. This subpopulation is representative for the whole LLS regarding disease prevalence and parameters involved in metabolic syndrome (Supplementary Table S5) Rozing et al, 2010). From these non-fasted individuals, peripheral blood was harvested using PAXgeneTM tubes (Qiagen, Venlo, the Netherlands).…”

Section: Sample Collection and Rna Preparationmentioning

confidence: 99%

Gene expression analysis of mTOR pathway: association with human longevity

et al. 2012

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SummarymTOR signalling is implicated in the development of disease and in lifespan extension in model organisms. This pathway has been associated with human diseases such as diabetes and cancer, but has not been investigated for its impact on longevity per se. Here, we investigated whether transcriptional variation within the mTOR pathway is associated with human longevity using whole‐blood samples from the Leiden Longevity Study. This is a unique cohort of Dutch families with extended survival across generations, decreased morbidity and beneficial metabolic profiles in middle‐age. By comparing mRNA levels of nonagenarians and middle‐aged controls, the mTOR signalling gene set was found to associate with old age (P = 4.6 × 10−7). Single gene analysis showed that seven of 40 mTOR pathway genes had a significant differential expression of at least 5%. Of these, the RPTOR (Raptor) gene was found to be differentially expressed also when the offspring of nonagenarians was compared with their spouses, indicating association with familial longevity in middle‐age. This association was not explained by variation between the groups in the prevalence of type 2 diabetes and cancer or glucose levels. Thus, the mTOR pathway not only plays a role in the regulation of disease and aging in animal models, but also in human health and longevity.

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Favorable Glucose Tolerance and Lower Prevalence of Metabolic Syndrome in Offspring without Diabetes Mellitus of Nonagenarian Siblings: The Leiden Longevity Study

Abstract: Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity.

Cited by 75 publications

References 26 publications

Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study

Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

Gene expression analysis of mTOR pathway: association with human longevity

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