Apolipoprotein B Variants and Exceptional Human Longevity

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Studies of human longevity-associated genes produce results that tend to be hard to replicate. The effects are individually tiny and vary widely between study populations, indicating a complex web of influences. Only a few genes stand out as having small and consistent rather than tiny and varying associations with longevity, such as APOE variants involved in the operation of cholesterol metabolism among other things. So on the one hand expect the results of this study to be hard to replicate, especially given the small sample size, but on the other hand it is somewhat connected to APOE so we shall see:

Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co-segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan. In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long-lived siblings (probands of more than 103 years and at least one sibling of more than 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have ≤ 1% minor allele frequency according to databases and that are likely to alter gene product function.
Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Interestingly, APOB is a component of lipoprotein particles together with APOE, and variants in the genes encoding these two proteins have been previously associated with human longevity. Analysis of nonfamilial EL cases showed a trend, without reaching statistical significance, toward enrichment of APOB RFVs. We have also identified candidate longevity genes shared between two families (5 - 13) or within individual families (66 - 156 genes). Some of these genes have been previously linked to longevity in model organisms, such as PPARGC1A, NRG1, RAD52, RAD51, NCOR1, and ADCY5 genes. This work provides an initial catalog of genes that could contribute to exceptional familial longevity.

Link: http://onlinelibrary.wiley.com/doi/10.1111/acel.12261/full