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Assessment of the contribution of APOE gene variants to metabolic phenotypes associated with familial longevity at middle age.

ABSTRACT: Offspring of long-lived families are characterized by beneficial metabolic phenotypes in glucose and lipid metabolism and low 25-hydroxyvitamin D. Although the genetic basis for human longevity remains largely unclear, the contribution of variation at the APOE locus has been repeatedly demonstrated. We aimed to assess whether ApoE isoforms mark the familial longevity status in middle age and subsequently to test to what extend this association is mediated by the metabolic characteristics marking this status. From the Leiden Longevity Study (LLS), we included offspring from nonagenarian siblings and partners as controls. Using the metabolic phenotypes of familial longevity as mediators, we investigated how APOE gene variants associated with LLS offspring/control status (in 1,515 LLS offspring and 715 controls). Within the LLS (mean age = 59.2 years), ApoE ?4 was not associated with a lower likelihood of being an LLS offspring, whereas ApoE ?2 was significantly associated with a higher likelihood of being an LLS offspring (odds ratio = 1.43), but this difference was not mediated (p-values>0.05) by any of the investigated metabolic phenotypes (e.g., diabetes and glucose). Therefore, variation at the APOE locus may not influence familial longevity status in middle age significantly through any of the metabolic mechanisms investigated.

SUBMITTER: Noordam R

PROVIDER: S-EPMC5032696 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Assessment of the contribution of APOE gene variants to metabolic phenotypes associated with familial longevity at middle age.

Noordam Raymond R Oudt Charlotte H CH Deelen Joris J Slagboom P Eline PE Beekman Marian M van Heemst Diana D

Aging 20160801 8

Offspring of long-lived families are characterized by beneficial metabolic phenotypes in glucose and lipid metabolism and low 25-hydroxyvitamin D. Although the genetic basis for human longevity remains largely unclear, the contribution of variation at the APOE locus has been repeatedly demonstrated. We aimed to assess whether ApoE isoforms mark the familial longevity status in middle age and subsequently to test to what extend this association is mediated by the metabolic characteristics marking ...[more]

PMID: 27540764

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Project description:BACKGROUND:In social insects, identical genotypes can show extreme lifespan variation providing a unique perspective on age-associated microbial succession. In honey bees, short- and long-lived host phenotypes are polarized by a suite of age-associated factors including hormones, nutrition, immune senescence, and oxidative stress. Similar to other model organisms, the aging gut microbiota of short-lived (worker) honey bees accrue Proteobacteria and are depleted of Lactobacillus and Bifidobacterium, consistent with a suite of host senescence markers. In contrast, long-lived (queen) honey bees maintain youthful cellular function with much lower expression of oxidative stress genes, suggesting a very different host environment for age-associated microbial succession. RESULTS:We sequenced the microbiota of 63 honey bee queens exploring two chronological ages and four alimentary tract niches. To control for genetic and environmental variation, we quantified carbonyl accumulation in queen fat body tissue as a proxy for biological aging. We compared our results to the age-specific microbial succession of worker guts. Accounting for queen source variation, two or more bacterial species per niche differed significantly by queen age. Biological aging in queens was correlated with microbiota composition highlighting the relationship of microbiota with oxidative stress. Queens and workers shared many major gut bacterial species, but differ markedly in community structure and age succession. In stark contrast to aging workers, carbonyl accumulation in queens was significantly associated with increased Lactobacillus and Bifidobacterium and depletion of various Proteobacteria. CONCLUSIONS:We present a model system linking changes in gut microbiota to diet and longevity, two of the most confounding variables in human microbiota research. The pattern of age-associated succession in the queen microbiota is largely the reverse of that demonstrated for workers. The guts of short-lived worker phenotypes are progressively dominated by three major Proteobacteria, but these same species were sparse or significantly depleted in long-lived queen phenotypes. More broadly, age-related changes in the honey bee microbiota reflect the regulatory anatomy of reproductive host metabolism. Our synthesis suggests that the evolution of colony-level reproductive physiology formed the context for host-microbial interactions and age-related succession of honey bee microbiota.

Dataset Information

Assessment of the contribution of APOE gene variants to metabolic phenotypes associated with familial longevity at middle age.

Publications

Assessment of the contribution of APOE gene variants to metabolic phenotypes associated with familial longevity at middle age.

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